{"paper_id":"27cd1861-7b5f-4e25-bd7d-a5a9dfd6a16f","body_text":"Contribution of Comorbid Pathologies to Amyotrophic Lateral Sclerosis with Cognitive or Behavioral Abnormalities | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Contribution of Comorbid Pathologies to Amyotrophic Lateral Sclerosis with Cognitive or Behavioral Abnormalities Hideyuki Moriyoshi, Akio Akagi, Yuichi Riku, Jun Sone, Hiroaki Miyahara, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7559940/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 03 Dec, 2025 Read the published version in BMC Neurology → Version 1 posted 10 You are reading this latest preprint version Abstract Background: Amyotrophic lateral sclerosis (ALS) often presents with cognitive or behavioral abnormalities. The cortical involvement of TAR DNA-binding protein-43 (TDP-43) pathology is considered a major cause of these abnormalities. However, the contribution of underlying comorbid pathologies remains unclear. Methods: We investigated the clinicopathological characteristics of 29 autopsy cases of ALS with cognitive or behavioral abnormalities and evaluated the association between clinical symptoms and comorbid pathologies such as Alzheimer’s disease (AD), argyrophilic grain disease (AGD), dementia with Lewy bodies (DLB), and primary age-related tauopathy (PART), as well as the presence of cortical TDP-43 pathology. Results: Of the 29 patients, 17 exhibited comorbid pathologies (AD, AGD, or PART), which may contribute to cognitive or behavioral abnormalities. None of the cases met the pathological criteria for DLB. The group with comorbid pathologies was significantly older, but clinical symptoms did not differ between the groups. Behavioral abnormalities and memory impairment were frequently observed in both groups. All six subjects without cortical TDP-43 pathology had comorbid pathologies, which had a notable effect on cognitive or behavioral abnormalities. Hippocampal sclerosis and memory impairment were observed in ALS cases without comorbid pathologies. Conclusion: A high frequency of comorbid pathologies is observed in elderly patients with ALS presenting with cognitive or behavioral abnormalities. There are cases of ALS in which comorbid pathologies such as AD, AGD, and PART may contribute to cognitive or behavioral abnormalities, even in the absence of cortical TDP-43 pathology. Hippocampal sclerosis of ALS may contribute to memory impairment independently of comorbid pathologies. Amyotrophic lateral sclerosis Alzheimer’s disease Argyrophilic grain disease Senile dementia of the neurofibrillary tangle type Primary age-related tauopathy Frontotemporal lobar degeneration Figures Figure 1 Figure 2 Background Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that affects the upper and lower motor neurons, leading to generalized muscle weakness and respiratory impairment [ 1 ]. Furthermore, cognitive or behavioral abnormalities occur in 30–50% of patients with ALS, and approximately 15% meet the diagnostic criteria for frontotemporal dementia [ 1 ]. The key pathological feature of ALS is the abnormal accumulation of TAR DNA-binding protein 43 (TDP-43) in the affected neurons [ 2 ] [ 3 ]. In patients with ALS and cognitive or behavioral abnormalities, TDP-43 pathology often extends beyond the motor neuron system into the frontotemporal lobe, overlapping with the pathological spectrum of frontotemporal lobar degeneration (FTLD) [ 4 ] [ 5 ]. TDP-43 pathology in the frontotemporal lobes is a major cause of cognitive or behavioral abnormalities in ALS. However, comorbid pathologies such as Alzheimer's disease (AD) also contribute to cognitive decline [ 6 ] [ 7 ]. The contribution of the comorbid pathology to ALS with cognitive or behavioral abnormalities remains unclear because postmortem examination is necessary for accurate diagnosis. Therefore, we aimed to clarify the contribution of comorbid pathologies to ALS with cognitive or behavioral abnormalities. Methods Subjects We screened the clinicopathological data of 153 consecutive autopsy cases of ALS from 2010 to 2023 at the Institute for Medical Science of Aging, Aichi Medical University. Of the 153 cases, 31 with clinically documented cognitive or behavioral abnormalities were included in this study. Two cases were excluded—one due to insufficient clinical data and tissue availability, and the other due to a preexisting self-directed personality. Thus, 29 cases were analyzed. All patients met the criteria for “possible” or more advanced categories according to the revised El Escorial criteria for ALS diagnosis [ 8 ]. Written informed consent was obtained from patients' relatives before the autopsy. The Research Ethics Committee of Aichi Medical University approved all investigations, which were conducted in accordance with all provisions of the Declaration of Helsinki. Clinical assessments We retrospectively assessed clinical information from medical records and clinicopathological conferences, including age at death, sex, total disease duration, onset time of cognitive or behavioral abnormalities, and initial motor symptoms. The cognitive or behavioral abnormalities were classified based on the clinical descriptions. The cognitive abnormalities were categorized into the following domains: language dysfunction, executive dysfunction, and memory disturbance [ 9 ]. Language dysfunction included cases clinically diagnosed with progressive non-fluent aphasia or semantic dementia. Executive dysfunction was defined as impairment in executive functions, such as planning, judgment, problem-solving, cognitive flexibility, which significantly interfered with work or daily life activities. Memory impairment was defined as disturbance of short-term memory or episodic memory. Behavioral abnormalities include disinhibition, irritability, personality changes, apathy, altered food preferences, and perseverative behaviors. Tissue preparation The left hemisphere of the brain and the spinal cord were fixed in 20% neutral-buffered formalin for at least 2 weeks. The left cerebral hemisphere was sectioned coronally at a thickness of 8 mm, the brainstem and spinal cord were sectioned transversely, and the cerebellum was sectioned sagittally at a thickness of 5 mm. Subsequently, the regions of interest were trimmed and embedded in paraffin. Sections of 9 µm thickness were prepared for hematoxylin-eosin (HE), Klüver-Barrera, and Gallyas-Braak staining. Sections of 4.5 µm thickness were prepared for immunohistochemical analysis. The primary antibodies used for immunohistochemistry were phosphorylated tau (1:4000, mouse monoclonal, clone AT-8; Thermo Scientific, Rockford, IL, USA), amyloid-β (1:1000, mouse monoclonal, clone 12B2; IBL, Gunma, Japan), phosphorylated α-synuclein (1:6000, mouse monoclonal, pSyn#64; Wako Pure Chemical Industries, Osaka, Japan), and phosphorylated TDP-43 (1:4000, rabbit polyclonal; Cosmo Bio, Tokyo, Japan). Neuropathological evaluation The pathological diagnosis of ALS was established based on neuronal loss and astrogliosis in the anterior horn of the spinal cord and the precentral gyrus in association with TDP-43 pathology (Fig. 1 A, B). We classified the cases into two subtypes (ALS types 1 and 2) based on their distribution pattern [ 4 ]. ALS type 1 is primarily localized to the motor neuron system, although a slight spread beyond the system occurs. ALS type 2 is characterized by the significant involvement of the frontotemporal cortex accompanied by cortical neuronal loss, astrogliosis, and microvacuolization (Fig. 1 C–E). Cortical TDP-43 pathology was classified into three subtypes according to the FTLD-TDP classification [ 10 ]. In addition, TDP-43 pathology was classified into five hierarchical stages based on previous reports [ 11 ] [ 12 ]. Hippocampal sclerosis (HS) in ALS was assessed based on neuronal loss and gliosis in the subiculum (Fig. 1 F) [ 13 ]. Comorbid pathology was assessed for AD, primary age-related tauopathy (PART), Lewy bodies disease (LBD), and argyrophilic grain disease (AGD). Neurofibrillary tangles (NFTs) were evaluated using Braak’s stage [ 14 ]. Amyloid-β deposition was evaluated in five stages according to the Thal phase [ 15 ]. The density of the senile plaque was classified into four grades according to the consortium to establish a registry for Alzheimer’s disease (CERAD) [ 16 ]. The neuropathological diagnosis of AD was made for at least intermediate AD neuropathologic change, according to the National Institute on Aging-Alzheimer’s Association criteria [ 17 ]. PART was assessed according to the proposed criteria by using Braak’s NFT stage. NFTs at Braak Stage III or higher were considered to contribute to cognitive or behavioral abnormalities corresponding to senile dementia of neurofibrillary tangle-type (SD-NFT) [ 18 ] [ 19 ] [ 20 ]. LBD was screened by HE staining to identify Lewy bodies in the dorsal motor nucleus of the vagus, locus coeruleus, substantia nigra, and amygdala. α-Synuclein immunostaining was conducted in the dorsal motor nucleus and amygdala, and if positive, further staining of the brainstem, limbic regions, and cortex was performed according to the guidelines [ 21 ]. AGD were categorized into three grades using Gallyas-Braak staining [ 22 ]. Statistical analyses Statistical analyses were performed using R software (version 4.4.1; R Foundation for Statistical Computing, Vienna, Austria). The clinical and pathological findings were compared using the Mann–Whitney U and Fisher’s exact tests for quantitative and qualitative variables, respectively. The significance level was set at 0.05 for comparisons between the two groups. All statistical analyses were two-sided. Results Table 1 compares the clinical and pathological features of ALS with and without comorbid pathologies. The study population was contained relatively older individuals, with a median age of 74 years, and included a slightly higher proportion of males. The median total duration was 40 months. In over 50% of the cases, cognitive or behavioral abnormalities appeared before the onset of motor symptoms. Notably, most initial motor symptoms began in the bulbar region. Behavioral abnormalities were the most common, observed in approximately 70% of the cases, followed by memory impairment in approximately 40%. Language impairment and executive dysfunction were observed in only a few cases. Approximately 80% of the cases were classified as ALS type 2. HS was observed in approximately 50% of the cases. Of the 29 cases, 17 had a comorbid pathology, such as AD, AGD, and PART, with Braak’s NFT stage Ⅲ. Four cases had a high-likelihood AD pathology, and five had an intermediate-likelihood AD pathology, totaling nine cases (Fig. 2A–F). AGD was diagnosed in four cases: two at stage I, and one each at stages II and III (Fig. 2G–I). Four cases of PART were classified as Braak’ NFT stage Ⅲ (Fig. 2J–L). None of the cases had α-synuclein pathology consistent with dementia with Lewy body, although one case showed a small number of α-synuclein positive structures in the medulla oblongata. The group with comorbid pathologies was significantly older than those without. The frequency of ALS type 2 was significantly higher in the group without comorbid pathology. No significant differences were observed between groups in sex distribution, disease duration, timing of dementia onset, initial motor symptoms (bulbar, upper limb, lower limb, respiratory muscles, or multiple regions), main cognitive symptoms (behavioral abnormalities, language impairment, executive dysfunction, or memory impairment), or the frequency of HS. Table 2 shows the clinicopathological profiles of the ALS cases with cognitive or behavioral abnormalities. All ALS type 1 cases exhibited comorbid pathology. Accordingly, the cases were classified into three groups based on the type of ALS and the presence of comorbid pathologies: ALS type 1 with comorbid pathology (Cases 1–6), ALS type 2 with comorbid pathology (Cases 7–17), and ALS type 2 without comorbid pathology (Cases 18–29). Behavioral abnormalities and memory impairment were present across all groups at a high frequency. In contrast, language impairment and executive dysfunction were observed only in cases with ALS type 2 pathology. Most ALS type 2 cases were classified as FTLD type B. HS was found in 14 out of the 23 ALS type 2 cases and was not observed in ALS type 1. Comorbid AD pathology was clinically suspected in three cases, with cognitive symptoms preceding the onset of motor symptoms. None of the patients had familial neurological disorders. Discussion Representative cortical involvement in ALS includes neuronal loss, astrogliosis, and superficial spongiosis [ 23 ]. Cognitive and behavioral abnormalities are significantly correlated with cortical TDP-43 pathology [ 4 ] [ 5 ] [ 24 ] [ 25 ]. In our cohort, 23 cases (79.3%) were classified as ALS type 2, with or without comorbid pathology. This finding suggests that most cognitive and behavioral abnormalities in ALS can be attributed to cortical involvement, which is consistent with previous reports. In contrast, six cases (20.7%) exhibited significant cognitive or behavioral abnormalities despite the absence of cortical TDP-43 pathology. This unexpected finding implies that additional pathological processes may underlie these symptoms. The overlap of neurodegenerative diseases is considered an important contributor to the heterogeneity of clinical symptoms [ 26 ]. Previous studies have reported that ALS is occasionally accompanied by additional neuropathological conditions, such as AD or LBD, which may complicate its clinical manifestations [ 6 , 27 ]. Hence, the presence of additional neuropathological findings, particularly in ALS type 1 cases, may reasonably be considered to contribute to cognitive or behavioral abnormalities in ALS. In this study, comorbid AD, AGD, and PART were identified in all six ALS cases without cortical involvement, suggesting their potential contribution to the observed cognitive and behavioral abnormalities. AD may be the most notable neuropathological contributor to cognitive or behavioral abnormalities in ALS [ 6 ] [ 7 ]. Previous reports have described cases of high-likelihood AD pathology in the absence of cortical ALS involvement [ 6 ]. AD is the most common form of dementia and typically presents with memory impairment, although atypical clinical variants have also been described [ 28 ]. In our case series, AD-related pathology was observed in nine cases (Cases 1–3 and 7–12). Memory impairment was observed in three out of the four high-likelihood AD pathology cases, suggesting that AD pathology contributed to the observed symptoms. In addition, behavioral abnormalities with or without memory impairment were observed in approximately two-thirds of the cases with AD pathology. Behavioral abnormalities may appear to differ from the typical clinical presentation of AD; however, AD can also manifest with behavioral and psychological symptoms, which are described separately from cognitive decline and are referred to as behavioral and psychological symptoms of dementia (BPSD) [ 29 ]. The causes of BPSD are multifactorial, including environmental and physical factors. Notably, AD pathology has been linked to the emergence of BPSD even in the early stages of disease [ 30 ] [ 31 ]. Furthermore, in addition to physical disability, psychosocial stress and pain are common clinical issues in patients with ALS [ 32 ] [ 33 ]. These clinical factors increase the risk of BPSD [ 34 ]. In these present ALS cases showing behavioral abnormalities with comorbid AD pathology, the observed symptoms may have been driven by the AD pathology, a possibility that may be underrecognized and may complicate the clinical interpretation of behavioral abnormalities in ALS. We found four (13.4%) cases with comorbid AGD pathology. ALS is sometimes accompanied by AGD [ 22 ]. And its contribution to the clinical manifestation of ALS remains unclear because AGD can be present in older adults with preserved cognitive function [ 35 ]. However, AGD was first described as non-AD dementia, and cognitive symptoms appear to be associated with AGD, especially in the advanced stage [ 22 ] [ 36 ]. In our series, only one case demonstrated AGD stage 3, and this case presented with memory impairment, which was consistent with the underlying pathology (Case 13). AGD has been associated with psychiatric symptoms [ 36 ] [ 37 ] [ 38 ], frequently with irritability [ 36 ]; bipolar disorder or late-onset schizophrenia [ 37 ] [ 38 ]; and psychiatric and cognitive symptoms, even at stage 2 or lower [ 37 ] [ 39 ]. Moreover, AGD is a risk factor for suicide regardless of the stage [ 40 ]. The amygdala is affected in the early stages of AGD, and the characteristic morphological features in this region include argyrophilic grains, ballooned neurons, granular fuzzy astrocytes, neuronal loss, and astrogliosis (Fig. 2 G–I) [ 22 ]. The occurrence of psychotic symptoms in AGD cases may be associated with the initial involvement of the limbic system, such as the amygdala [ 37 ] [ 40 ]. Therefore, the development of behavioral abnormalities in the ALS type 1 cases with AGD stage 2 can be attributed to the underlying AGD pathology (Case 4). PART is a pathological concept that describes limbic-predominant tau pathology in the absence of amyloid plaques, representing a continuum from cognitively normal aged individuals to those with dementia and encompasses SD-NFT [ 19 ]. Since PART is commonly identified at autopsy among elderly individuals without dementia, its contribution to cognitive symptoms should be interpreted carefully. SD-NFT is a form of dementia characterized by abundant NFTs in the limbic regions without amyloid-β deposition [ 18 ] [ 41 ]. Most patients diagnosed with SD-NFT are classified as NFT Braak stages III and IV [ 42 ] [ 43 ]. When comorbid pathology of PART NFT Braak stage III and IV is observed in autopsy cases of patients with dementia, its potential association with clinical dementia symptoms needs to be carefully considered as SD-NFT. The clinical presentation of SD-NFT resembles that of AD, and many cases are likely to be clinically misdiagnosed as AD unless confirmed by autopsy [ 43 ]. The progression of SD-NFT is generally slower than that of AD, and behavioral abnormalities emerge in the later stages of the disease [ 18 ] [ 41 ]. However, in psychiatric hospital cohorts, psychiatric symptoms, such as delusions, are common in SD-NFT, and the clinical manifestations observed in such cases may reflect the characteristics of the underlying cohort [ 42 ]. In our study, two ALS type 1 cases with PART, both classified as NFT Braak stage III, presented with behavioral abnormalities (Cases 5 and 6). A direct causal relationship cannot be established due to the mild degree of PART pathology and behavioral abnormalities are not specific symptom of SD-NFT. However, the presence of PART pathology in ALS type 1 cases with behavioral abnormalities suggests that its role in ALS should not be underestimated. Memory impairment is not considered a specific cognitive symptom of ALS [ 9 ]. Initially, we hypothesized that memory impairment is significantly associated with comorbid pathologies. However, our results did not support this hypothesis, as approximately 40% of ALS type 2 cases without comorbid pathology exhibited memory impairment. Memory impairment is occasionally observed in patients with ALS and has been linked to hippocampal atrophy on neuroimaging [ 44 ] [ 45 ]. Advanced degeneration of the hippocampal perforant pathway, including the entorhinal region and subiculum in ALS, is associated with memory disturbances and mimics AD [ 13 ]. In this study, three of the five ALS type 2 cases without comorbid pathology or cases with memory impairment showed prominent HS (Cases 22, 23, and 28). These findings suggest that HS may contribute to memory impairment in ALS independent of comorbid pathologies. Thus, memory impairment did not reliably predict comorbid pathologies. The coexistence of ALS with Lewy body disease is rare but occasionally observed [ 27 ]. Previous reports have described ALS cases with α-synuclein pathology presenting with parkinsonism or orthostatic hypotension, suggesting that the comorbidity of α-synuclein pathology may influence the clinical manifestations of ALS[ 27 ] [ 46 ]. However, in the present study, only one case exhibited a small number of α-synuclein-positive structures in the medulla oblongata; this case was regarded as an incidental finding or prodromal Parkinson’s disease, with little association with clinical symptoms. This study has some limitations. Whether these comorbid pathologies contribute to developing cognitive or behavioral symptoms remains a matter of discussion. The prevalence of comorbid pathology was significantly higher among older individuals. AD, AGD, and PART pathologies have also been observed in cognitively unimpaired older individuals [ 47 ]. Therefore, these pathologies may represent age-related changes rather than pathological contributors in older patients with ALS. The sample size was small, and further classification by ALS type and comorbid pathology led to even smaller subgroups, precluding meaningful subgroup analyses. Due to the retrospective nature of this study, causal relationships could not be established. Cognitive symptoms were assessed based on clinical descriptions rather than standardized neuropsychological testing, which may have introduced variability in interpretation and reduced objectivity. In addition, selection bias related to autopsy consent may have been present. Despite these limitations, our autopsy-based findings provide important insights into the potential contribution of comorbid pathologies to ALS with cognitive and behavioral abnormalities. To determine the contribution of comorbid pathologies to cognitive and behavioral abnormalities in ALS, prospective studies with larger cohorts, standardized cognitive assessments, and comparisons with appropriate control groups are needed. Conclusion A high frequency of comorbid pathologies is observed in elderly patients with ALS with cognitive or behavioral abnormalities. There are cases of ALS in which comorbid pathologies such as AD, AGD, and PART may contribute to cognitive or behavioral abnormalities, even in the absence of cortical TDP-43 pathology. HS of ALS may contribute to memory impairment independently of comorbid pathologies. These findings highlight the clinicopathological complexity of cognitive and behavioral manifestations in ALS and emphasize the need for comprehensive pathological evaluation. In the clinical practice of the ALS with cognitive or behavioral abnormalities, such symptoms are typically attributed to cortical TDP-43 pathology; however, the contribution of comorbid pathologies should not be underestimated. Abbreviations AD Alzheimer’s disease AGD argyrophilic grain disease ALS amyotrophic lateral sclerosis BPSD behavioral and psychological symptoms of dementia DLB dementia with Lewy bodies CERAD consortium to establish a registry for Alzheimer’s disease FTLD frontotemporal lobar degeneration HE Hematoxylin and eosin HS hippocampal sclerosis IHC Immunohistochemistry LBD Lewy body disease NA not available NFT neurofibrillary tangle NIA-AA National Institute for Aging-Alzheimer Association PART primary age-related tauopathy pTau phosphorylated tau TDP-43 transactive response DNA-binding protein 43. Declarations Ethics approval and consent to participate The Research Ethics Committee of Aichi Medical University approved all investigations, which were conducted in accordance with all provisions of the Declaration of Helsinki. Written informed consent was obtained from patients' relatives before the autopsy. Consent for publication Written informed consent was obtained from patients' relatives before the autopsy. Availability of data and materials The datasets used or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding This work was supported by AMED under Grant Number JP24wm0625301 (M.K.), MHLW Research on rare and intractable diseases Program Grant Number JPMH23FC1008(M.K.), and Grants-in-Aid from the Research Committee of CNS Degenerative Diseases, Research on Policy Planning and Evaluation for Rare and Intractable Diseases, Health, Labour and Welfare Sciences Research Grants, Ministry of Health, Labour and Welfare, Japan (Y. Iwasaki). Authors' contributions HMo contributed to conceptualization, methodology, validation, formal analysis, investigation, resources, data curation, writing – original draft, and visualization. AA, YR, JS, HMi, and MY contributed to investigation and resources. MK contributed to conceptualization, methodology, supervision, and funding acquisition. YI contributed to conceptualization, methodology, validation, formal analysis, investigation, resources, data curation, writing – review & editing, visualization, supervision, project administration, and funding acquisition. All authors read and approved the final manuscript. Declaration of competing interest The authors declare no conflicts of interest. Acknowledgments We thank all patients, their families, and clinicians who referred patients to our institute. We also express our gratitude to Chizuko Sano, and Chieko Uno for their technical support during pathologic analyses. References Feldman EL, Goutman SA, Petri S, Mazzini L, Savelieff MG, Shaw PJ, et al. Amyotrophic lateral sclerosis. Lancet. 2022;400:1363-80. doi: 10.1016/s0140-6736(22)01272-7. Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science. 2006;314:130-3. doi: 10.1126/science.1134108. Arai T, Hasegawa M, Akiyama H, Ikeda K, Nonaka T, Mori H, et al. TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun. 2006;351:602-11. doi: 10.1016/j.bbrc.2006.10.093. Nishihira Y, Tan CF, Onodera O, Toyoshima Y, Yamada M, Morita T, et al. Sporadic amyotrophic lateral sclerosis: two pathological patterns shown by analysis of distribution of TDP-43-immunoreactive neuronal and glial cytoplasmic inclusions. Acta Neuropathol. 2008;116:169-82. doi: 10.1007/s00401-008-0385-z. Brettschneider J, Libon DJ, Toledo JB, Xie SX, McCluskey L, Elman L, et al. Microglial activation and TDP-43 pathology correlate with executive dysfunction in amyotrophic lateral sclerosis. Acta Neuropathol. 2012;123:395-407. doi: 10.1007/s00401-011-0932-x. Hamilton RL, Bowser R. Alzheimer disease pathology in amyotrophic lateral sclerosis. Acta Neuropathol. 2004;107:515-22. doi: 10.1007/s00401-004-0843-1. Verde F, Aiello EN, Adobbati L, Poletti B, Solca F, Tiloca C, et al. Coexistence of Amyotrophic Lateral Sclerosis and Alzheimer's Disease: Case Report and Review of the Literature. J Alzheimers Dis. 2023;95:1383-99. doi: 10.3233/jad-230562. Brooks BR, Miller RG, Swash M, Munsat TL. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord. 2000;1:293-9. doi: 10.1080/146608200300079536. Strong MJ, Abrahams S, Goldstein LH, Woolley S, McLaughlin P, Snowden J, et al. Amyotrophic lateral sclerosis - frontotemporal spectrum disorder (ALS-FTSD): Revised diagnostic criteria. Amyotroph Lateral Scler Frontotemporal Degener. 2017;18:153-74. doi: 10.1080/21678421.2016.1267768. Mackenzie IR, Neumann M, Baborie A, Sampathu DM, Du Plessis D, Jaros E, et al. A harmonized classification system for FTLD-TDP pathology. Acta Neuropathol. 2011;122:111-3. doi: 10.1007/s00401-011-0845-8. Brettschneider J, Del Tredici K, Toledo JB, Robinson JL, Irwin DJ, Grossman M, et al. Stages of pTDP-43 pathology in amyotrophic lateral sclerosis. Ann Neurol. 2013;74:20-38. doi: 10.1002/ana.23937. Brettschneider J, Arai K, Del Tredici K, Toledo JB, Robinson JL, Lee EB, et al. TDP-43 pathology and neuronal loss in amyotrophic lateral sclerosis spinal cord. Acta Neuropathol. 2014;128:423-37. doi: 10.1007/s00401-014-1299-6. Takeda T, Uchihara T, Arai N, Mizutani T, Iwata M. Progression of hippocampal degeneration in amyotrophic lateral sclerosis with or without memory impairment: distinction from Alzheimer disease. Acta Neuropathol. 2009;117:35-44. doi: 10.1007/s00401-008-0447-2. Braak H, Alafuzoff I, Arzberger T, Kretzschmar H, Del Tredici K. Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol. 2006;112:389-404. doi: 10.1007/s00401-006-0127-z. Thal DR, Rüb U, Orantes M, Braak H. Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology. 2002;58:1791-800. doi: 10.1212/wnl.58.12.1791. Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, et al. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology. 1991;41:479-86. doi: 10.1212/wnl.41.4.479. Hyman BT, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Carrillo MC, et al. National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease. Alzheimers Dement. 2012;8:1-13. doi: 10.1016/j.jalz.2011.10.007. Yamada M. Senile dementia of the neurofibrillary tangle type (tangle-only dementia): neuropathological criteria and clinical guidelines for diagnosis. Neuropathology. 2003;23:311-7. doi: 10.1046/j.1440-1789.2003.00522.x. Crary JF, Trojanowski JQ, Schneider JA, Abisambra JF, Abner EL, Alafuzoff I, et al. Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathol. 2014;128:755-66. doi: 10.1007/s00401-014-1349-0. Jellinger KA, Alafuzoff I, Attems J, Beach TG, Cairns NJ, Crary JF, et al. PART, a distinct tauopathy, different from classical sporadic Alzheimer disease. Acta Neuropathol. 2015;129:757-62. doi: 10.1007/s00401-015-1407-2. McKeith IG, Boeve BF, Dickson DW, Halliday G, Taylor JP, Weintraub D, et al. Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. Neurology. 2017;89:88-100. doi: 10.1212/wnl.0000000000004058. Saito Y, Ruberu NN, Sawabe M, Arai T, Tanaka N, Kakuta Y, et al. Staging of argyrophilic grains: an age-associated tauopathy. J Neuropathol Exp Neurol. 2004;63:911-8. doi: 10.1093/jnen/63.9.911. Mitsuyama Y. Presenile dementia with motor neuron disease in Japan: clinico-pathological review of 26 cases. J Neurol Neurosurg Psychiatry. 1984;47:953-9. doi: 10.1136/jnnp.47.9.953. Takeuchi R, Tada M, Shiga A, Toyoshima Y, Konno T, Sato T, et al. Heterogeneity of cerebral TDP-43 pathology in sporadic amyotrophic lateral sclerosis: Evidence for clinico-pathologic subtypes. Acta Neuropathol Commun. 2016;4:61. doi: 10.1186/s40478-016-0335-2. Suzuki Y, Adachi T, Yoshida K, Sakuwa M, Hanajima R. Psychiatric symptoms and TDP-43 pathology in amyotrophic lateral sclerosis. J Neurol Sci. 2024;466:123249. doi: 10.1016/j.jns.2024.123249. Armstrong RA, Lantos PL, Cairns NJ. Overlap between neurodegenerative disorders. Neuropathology. 2005;25:111-24. doi: 10.1111/j.1440-1789.2005.00605.x. Forrest SL, Kim JH, De Sousa C, Cheong R, Crockford DR, Sheedy D, et al. Coexisting Lewy body disease and clinical parkinsonism in amyotrophic lateral sclerosis. Eur J Neurol. 2021;28:2192-9. doi: 10.1111/ene.14849. Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chételat G, Teunissen CE, et al. Alzheimer's disease. Lancet. 2021;397:1577-90. doi: 10.1016/s0140-6736(20)32205-4. Ismail Z, Creese B, Aarsland D, Kales HC, Lyketsos CG, Sweet RA, et al. Psychosis in Alzheimer disease - mechanisms, genetics and therapeutic opportunities. Nat Rev Neurol. 2022;18:131-44, doi: 10.1038/s41582-021-00597-3. Farber NB, Rubin EH, Newcomer JW, Kinscherf DA, Miller JP, Morris JC, et al. Increased neocortical neurofibrillary tangle density in subjects with Alzheimer disease and psychosis. Arch Gen Psychiatry. 2000;57:1165-73. doi: 10.1001/archpsyc.57.12.1165. Ehrenberg AJ, Suemoto CK, França Resende EP, Petersen C, Leite REP, Rodriguez RD, et al. Neuropathologic Correlates of Psychiatric Symptoms in Alzheimer's Disease. J Alzheimers Dis. 2018;66:115-26. doi: 10.3233/jad-180688. Felgoise SH, Chakraborty BH, Bond E, Rodriguez J, Bremer BA, Walsh SM, et al. Psychological morbidity in ALS: the importance of psychological assessment beyond depression alone. Amyotroph Lateral Scler. 2010;11:351-8. doi: 10.3109/17482961003667630. Chiò A, Mora G, Lauria G. Pain in amyotrophic lateral sclerosis. Lancet Neurol. 2017;16:144-57. doi: 10.1016/s1474-4422(16)30358-1. Kales HC, Gitlin LN, Lyketsos CG. Assessment and management of behavioral and psychological symptoms of dementia. Bmj. 2015;350:h369. doi: 10.1136/bmj.h369. Josephs KA, Whitwell JL, Parisi JE, Knopman DS, Boeve BF, Geda YE, et al. Argyrophilic grains: a distinct disease or an additive pathology? Neurobiol Aging. 2008;29:566-73. doi: 10.1016/j.neurobiolaging.2006.10.032. Togo T, Isojima D, Akatsu H, Suzuki K, Uchikado H, Katsuse O, et al. Clinical features of argyrophilic grain disease: a retrospective survey of cases with neuropsychiatric symptoms. Am J Geriatr Psychiatry. 2005;13:1083-91. doi: 10.1176/appi.ajgp.13.12.1083. Nagao S, Yokota O, Ikeda C, Takeda N, Ishizu H, Kuroda S, et al. Argyrophilic grain disease as a neurodegenerative substrate in late-onset schizophrenia and delusional disorders. Eur Arch Psychiatry Clin Neurosci. 2014;264:317-31. doi: 10.1007/s00406-013-0472-6. Shioya A, Saito Y, Arima K, Kakuta Y, Yuzuriha T, Tanaka N, et al. Neurodegenerative changes in patients with clinical history of bipolar disorders. Neuropathology. 2015;35:245-53. doi: 10.1111/neup.12191. Wurm R, Klotz S, Rahimi J, Katzenschlager R, Lindeck-Pozza E, Regelsberger G, et al. Argyrophilic grain disease in individuals younger than 75 years: clinical variability in an under-recognized limbic tauopathy. Eur J Neurol. 2020;27:1856-66. doi: 10.1111/ene.14321. Yoshida K, Hata Y, Ichimata S, Okada K, Nishida N. Argyrophilic grain disease is common in older adults and may be a risk factor for suicide: a study of Japanese forensic autopsy cases. Transl Neurodegener. 2023;12:16. doi: 10.1186/s40035-023-00352-2. Jellinger KA, Attems J. Neurofibrillary tangle-predominant dementia: comparison with classical Alzheimer disease. Acta Neuropathol. 2007;113:107-17. doi: 10.1007/s00401-006-0156-7. Kawakami I, Hasegawa M, Arai T, Ikeda K, Oshima K, Niizato K, et al. Tau accumulation in the nucleus accumbens in tangle-predominant dementia. Acta Neuropathol Commun. 2014;2:40. doi: 10.1186/2051-5960-2-40. Tahara N, Tahara D, Akagi A, Riku Y, Sone J, Miyahara H, et al. Hippocampal sclerosis in senile dementia of the neurofibrillary tangle type. J Neurol Sci. 2025;471:123437. doi: 10.1016/j.jns.2025.123437. Abdulla S, Machts J, Kaufmann J, Patrick K, Kollewe K, Dengler R, et al. Hippocampal degeneration in patients with amyotrophic lateral sclerosis. Neurobiol Aging. 2014;35:2639-45. doi: 10.1016/j.neurobiolaging.2014.05.035. Raaphorst J, van Tol MJ, de Visser M, van der Kooi AJ, Majoie CB, van den Berg LH, et al. Prose memory impairment in amyotrophic lateral sclerosis patients is related to hippocampus volume. Eur J Neurol. 2015;22:547-54. doi: 10.1111/ene.12615. Yamada T, Itoh K, Matsuo K, Yamamoto Y, Hosokawa Y, Koizumi T, et al. Concomitant alpha-synuclein pathology in an autopsy case of amyotrophic lateral sclerosis presenting with orthostatic hypotension and cardiac arrests. Neuropathology. 2014;34:164-9. doi: 10.1111/neup.12057. Knopman DS, Parisi JE, Salviati A, Floriach-Robert M, Boeve BF, Ivnik RJ, et al. Neuropathology of cognitively normal elderly. J Neuropathol Exp Neurol. 2003;62:1087-95. doi: 10.1093/jnen/62.11.1087. Tables Table 1 Comparison of clinical and pathological features between the amyotrophic lateral sclerosis (ALS) cases with or without comorbid pathology. Total N=29 Comorbid pathology (-) N=12 Comorbid pathology (+) N=17 P value Age at death (years) 74 (68–79) 68 (58–76) 76 (71–79) 0.048 Sex (male) 19 (65) 7 (58.3) 12 (70.6) 0.694 Total disease duration (months) 40 (21.5–108.75) 39 (22.5–87.5) 47 (20–133) 0.925 Onset of cognitive or behavioral abnormality before motor symptom 15 (51.7) 6 (50.0) 9 (52.9) 1.000 after motor symptom 5 (17.2) 2 (16.7) 3 (17.6) 1.000 simultaneous 5 (17.2) 1 (8.3) 4 (23.5) 0.370 NA 4 (13.8) 3 (25.0) 1 (5.9) 0.279 Initial motor symptom bulbar 14 (48.3) 5 (41.7) 9 (52.9) 0.710 upper 6 (20.7) 5 (41.7) 1 (5.9) 0.056 lower 4 (13.8) 1 (8.3) 3 (17.6) 0.622 respiratory 1 (3.4) 0 1 (5.9) 1.000 multiple domains 2 (6.9) 0 2 (11.8) 0.498 NA 2 (6.9) 1 (8.3) 1 (5.9) 1.000 Main cognitive or behavioral symptom behavioral abnormality 20 (69.0) 8 (66.7) 12 (70.6) 1.000 language dysfunction 3 (10.3) 0 3 (17.6) 0.246 executive dysfunction 2 (6.9) 2 (16.7) 0 0.163 memory impairment 11 (37.9) 5 (41.7) 7 (41.2) 1.000 ALS type2 pathology 23 (79.3) 12 (100) 11 (64.7) 0.028 Hippocampal sclerosis 14 (48.3) 6 (50.0) 8 (47.1) 1.000 Comorbid pathology AD 9 (31.0) - 9 (52.9) - AGD 4 (13.8) - 4 (23.5) - PART (≧ Braak NFT stage Ⅲ) 4 (13.8) - 4 (23.5) - Values are presented as n (%) or median (IQR). Statistical analysis was performed using the Mann–Whitney U test for age at death and disease duration, and Fisher’s test for other variables. Table 2 Clinicopathological profile of ALS cases with cognitive or behavioral abnormalities. Case ALS subtype Comorbid pathology Age at death Sex Disease duration (months) Main cognitive or behavioral symptoms Stage of TDP-43 pathology FTLD subtype HS NFT Braak stage Aβ Thal Phase senile plaque NIA-AA AD likelihood AGD stage α-synuclein behavioral abnormality language dysfunction executive dysfunction memory impairment 1 Type 1 AD 85 F 324 + - - + 1 - - Ⅴ 5 Frequent High - - 2 Type 1 AD 79 M 12 + - - - 3 - - Ⅲ 3 Moderate Intermediate - - 3 Type 1 AD 79 M 20 - - - + 2 - - Ⅲ 3 Sparse Intermediate - Brainstem 4 Type 1 AGD 68 F 23 + - - - 3 - - Ⅲ 1 Sparse Not 2 - 5 Type 1 PART ※ 71 F 62 + - - - 1 - - Ⅲ - None Not - - 6 Type 1 PART ※ 78 F 140 + - - - 3 - - Ⅲ - None Not - - 7 Type 2 AD 89 F 239 + - - - 4 Type B - Ⅵ 5 Moderate High - - 8 Type 2 AD 77 M 47 + + - + 4 Type B + Ⅵ 5 Moderate High - - 9 Type 2 AD 75 M 60 - - - + 4 Type B + Ⅴ 5 Frequent High - - 10 Type 2 AD 85 M 6 - + - - 4 Type B + Ⅲ 3 Moderate Intermediate - - 11 Type 2 AD 74 M 23 + - - - 5 Type B + Ⅲ 4 Sparse Intermediate - - 12 Type 2 AD 71 M 36 + - - - 5 Type B + Ⅲ 5 Frequent Intermediate - - 13 Type 2 AGD 76 M 4 - - - + 4 Type B + Ⅲ - None Not 3 - 14 Type 2 AGD 80 M 137 + - - - 4 Type B + Ⅱ - None Not 1 - 15 Type 2 AGD 65 M 69 + + - - 4 Type B - Ⅰ 2 Sparse Low 1 - 16 Type 2 PART ※ 70 F 133 - - - + 4 Type B + Ⅲ - None Not - - 17 Type 2 PART ※ 69 M 10 + - - - 5 Type B - Ⅲ 1 None Low - - ※PART is described as a comorbid pathology with Braak NFT stage 3 or higher Table2 (continued) Case ALS subtype Comorbid pathology Age at death Sex Disease duration (months) Main cognitive or behavioral symptoms Stage of TDP-43 pathology FTLD subtype HS NFT Braak stage Aβ Thal Phase senile plaque NIA-AA AD likelihood AGD stage α-synuclein behavioral abnormality language dysfunction executive dysfunction memory impairment 18 Type 2 - 45 M 11 - - + + 4 Type B - Ⅰ - None Not - - 19 Type 2 - 88 F 108 + - - - 4 Type B + Ⅰ 2 Moderate Low - - 20 Type 2 - 68 M 23 + - - - 4 Type B - Ⅰ - None Not - - 21 Type 2 - 68 F 19 + - - - 4 Type B - Ⅰ 2 None Not - - 22 Type 2 - 79 M 111 - - - + 4 Type B + Ⅱ - None Not - - 23 Type 2 - 58 F 22 - - + + 4 Type B + Ⅱ 3 Moderate Low - - 24 Type 2 - 70 F 39 + - - - 4 Type B - Ⅰ - None Not - - 25 Type 2 - 75 F NA + - - - 4 Type B + Ⅰ - None Not - - 26 Type 2 - 83 M 156 + - - + 4 Type A - Ⅱ - None Not - - 27 Type 2 - 66 M 67 + - - - 4 Type A + Ⅱ - None Not - - 28 Type 2 - 58 M 29 - - - + 5 Type B + Ⅰ - None Not - - 29 Type 2 - 45 M 41 + - - - 5 Type B - Ⅰ 1 None Not - - Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 03 Dec, 2025 Read the published version in BMC Neurology → Version 1 posted Editorial decision: Revision requested 14 Oct, 2025 Reviews received at journal 05 Oct, 2025 Reviews received at journal 29 Sep, 2025 Reviewers agreed at journal 18 Sep, 2025 Reviewers agreed at journal 18 Sep, 2025 Reviewers invited by journal 18 Sep, 2025 Editor invited by journal 15 Sep, 2025 Editor assigned by journal 08 Sep, 2025 Submission checks completed at journal 08 Sep, 2025 First submitted to journal 08 Sep, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-7559940\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":522141212,\"identity\":\"ef30477f-3703-4d2d-b96a-5dc688d75119\",\"order_by\":0,\"name\":\"Hideyuki Moriyoshi\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Aichi Medical University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Hideyuki\",\"middleName\":\"\",\"lastName\":\"Moriyoshi\",\"suffix\":\"\"},{\"id\":522141213,\"identity\":\"b819290b-d71f-41cf-a284-6a82341319ae\",\"order_by\":1,\"name\":\"Akio Akagi\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Aichi Medical University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Akio\",\"middleName\":\"\",\"lastName\":\"Akagi\",\"suffix\":\"\"},{\"id\":522141214,\"identity\":\"0360b756-6c8f-4602-8795-c0015b21c57d\",\"order_by\":2,\"name\":\"Yuichi Riku\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Aichi Medical University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Yuichi\",\"middleName\":\"\",\"lastName\":\"Riku\",\"suffix\":\"\"},{\"id\":522141215,\"identity\":\"791e70a2-4556-464c-9415-0305a9676ebb\",\"order_by\":3,\"name\":\"Jun Sone\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Aichi Medical University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Jun\",\"middleName\":\"\",\"lastName\":\"Sone\",\"suffix\":\"\"},{\"id\":522141216,\"identity\":\"edffd3b8-78c2-455a-bb13-312a39377b9e\",\"order_by\":4,\"name\":\"Hiroaki Miyahara\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Aichi Medical University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Hiroaki\",\"middleName\":\"\",\"lastName\":\"Miyahara\",\"suffix\":\"\"},{\"id\":522141217,\"identity\":\"f17725d6-847b-47eb-abab-ecd96c6d2601\",\"order_by\":5,\"name\":\"Mari Yosida\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Aichi Medical University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Mari\",\"middleName\":\"\",\"lastName\":\"Yosida\",\"suffix\":\"\"},{\"id\":522141218,\"identity\":\"8131dfed-63c1-49af-bf0f-d6f418680b96\",\"order_by\":6,\"name\":\"Masahisa Katsuno\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Nagoya University Graduate School of Medicine\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Masahisa\",\"middleName\":\"\",\"lastName\":\"Katsuno\",\"suffix\":\"\"},{\"id\":522141219,\"identity\":\"8e82b977-6df2-41c7-95ce-a3e0cfa9cd9c\",\"order_by\":7,\"name\":\"Yasushi Iwasaki\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABB0lEQVRIiWNgGAWjYBACNjB5QEIOSCZgSuDTYgwkHyAL4dYCAQcYEhsYGFG04AZ8EsmPP/w4Y5E+v/1wAuOPCoY8fvkGtgcfGPjycDpMIs1MsueGRO6GM2kJzDxnGIol2xjYDWcwsBXj1CKdYMbA8wGoRYIngZmx7X/ihmNAQR4GNqBTcWlJ//zxzweJdPkZ/B8Yf7YxJO4HafmDV0uOgTTPDYkEhhvAQOYFatnABhRkwKdF/k2ZtMwZCcMNZxISDgP9kjjjWGKbZI8Bbr/I9xzf/PHNsTp5+fYDiQ+BIZbY33z4mMSPimM4QwwFHIBQjEAnGRxLIEoLMqghXcsoGAWjYBQMVwAAUhFRPsOpWhUAAAAASUVORK5CYII=\",\"orcid\":\"\",\"institution\":\"Aichi Medical University\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Yasushi\",\"middleName\":\"\",\"lastName\":\"Iwasaki\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2025-09-08 04:38:36\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-7559940/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-7559940/v1\",\"draftVersion\":[],\"editorialEvents\":[{\"content\":\"https://doi.org/10.1186/s12883-025-04556-z\",\"type\":\"published\",\"date\":\"2025-12-03T15:58:19+00:00\"}],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":92499133,\"identity\":\"989eafbb-00c3-4039-b00c-8c07c880e5fc\",\"added_by\":\"auto\",\"created_at\":\"2025-09-30 10:57:19\",\"extension\":\"docx\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"acdc-reference\",\"size\":1490643,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7559940/v1/2a6d51fa5069894417c4b554.docx\"},{\"id\":92499128,\"identity\":\"1bb7df8e-bbe0-44a7-b2d7-862b2949f7d7\",\"added_by\":\"auto\",\"created_at\":\"2025-09-30 10:57:19\",\"extension\":\"json\",\"order_by\":1,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"acdc-reference\",\"size\":9678,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"00e1d6ba3d594f1bb7efebee50f0a821.json\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7559940/v1/5402966109aacefcdc026a2a.json\"},{\"id\":92499134,\"identity\":\"ba831149-66e9-440a-b5ee-636b0fab0415\",\"added_by\":\"auto\",\"created_at\":\"2025-09-30 10:57:19\",\"extension\":\"xml\",\"order_by\":2,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"acdc-reference\",\"size\":177712,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"00e1d6ba3d594f1bb7efebee50f0a8211enriched.xml\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7559940/v1/96fbe80ac798591acd760454.xml\"},{\"id\":92499476,\"identity\":\"cfb5a1b6-4b08-4df6-a05a-7ee59220a340\",\"added_by\":\"auto\",\"created_at\":\"2025-09-30 11:05:19\",\"extension\":\"jpeg\",\"order_by\":3,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"acdc-reference\",\"size\":443178,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"floatimage1.jpeg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7559940/v1/70d4a96b1f7108e4a3bbd445.jpeg\"},{\"id\":92499477,\"identity\":\"04aee4b7-ae8a-4da5-ba74-3c969172879b\",\"added_by\":\"auto\",\"created_at\":\"2025-09-30 11:05:19\",\"extension\":\"jpeg\",\"order_by\":4,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"acdc-reference\",\"size\":980636,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"floatimage2.jpeg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7559940/v1/7a2152f8846c81b151f41b18.jpeg\"},{\"id\":92499131,\"identity\":\"5252ff85-9afa-4097-a2f7-5a400ba23d24\",\"added_by\":\"auto\",\"created_at\":\"2025-09-30 10:57:19\",\"extension\":\"png\",\"order_by\":5,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"acdc-reference\",\"size\":250009,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"Onlinefloatimage1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7559940/v1/0ef6236ffcb2eb63b1c239f7.png\"},{\"id\":92499135,\"identity\":\"217a6ce6-fac0-4a07-bbbb-4a5e176152f0\",\"added_by\":\"auto\",\"created_at\":\"2025-09-30 10:57:19\",\"extension\":\"png\",\"order_by\":6,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"acdc-reference\",\"size\":473496,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"Onlinefloatimage2.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7559940/v1/bb7a17c0e5076bc6955133ae.png\"},{\"id\":92499136,\"identity\":\"8237b6c1-4168-4a04-88f1-1e57d259148f\",\"added_by\":\"auto\",\"created_at\":\"2025-09-30 10:57:19\",\"extension\":\"xml\",\"order_by\":7,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"acdc-reference\",\"size\":176146,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"00e1d6ba3d594f1bb7efebee50f0a8211structuring.xml\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7559940/v1/9c6b23a9133fecf516cf8920.xml\"},{\"id\":92499137,\"identity\":\"3db28ee5-1600-4319-8795-e4008930a518\",\"added_by\":\"auto\",\"created_at\":\"2025-09-30 10:57:19\",\"extension\":\"html\",\"order_by\":8,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"acdc-reference\",\"size\":183346,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"earlyproof.html\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7559940/v1/b54c89fd89ac9b275322e9a5.html\"},{\"id\":92499127,\"identity\":\"63d609b8-5a0d-4758-9cb3-9cf66e03e234\",\"added_by\":\"auto\",\"created_at\":\"2025-09-30 10:57:19\",\"extension\":\"png\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":330140,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eMicroscopic appearance of amyotrophic lateral sclerosis (ALS) type 2. (A, C, F) Hematoxylin and eosin staining. (B, D–E) Immunohistochemistry for phosphorylated TAR binding protein 43 (pTDP-43). (A) Severe neuronal loss and astrogliosis of the anterior horn of the cervical spinal cord. (B) Abnormal cytoplasmic accumulation of pTDP-43 in the anterior horn of the cervical spinal cord. (C) Microvacuolization of superior layer of temporal lobe. (D) Abnormal cytoplasmic accumulation of pTDP-43 of temporal cortex. (E) Abnormal cytoplasmic accumulation of pTDP-43 in the hippocampal dentate gyrus. (F) Hippocampal sclerosis characterized by severe neuronal loss and astrogliosis in the subiculum. Bar = 200 μm (F), 50 μm (A, C–E), 20 μm (B).\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7559940/v1/bd20e3500db62c20e5591951.png\"},{\"id\":92499129,\"identity\":\"586a7f02-9da7-4829-a093-c4212e77accf\",\"added_by\":\"auto\",\"created_at\":\"2025-09-30 10:57:19\",\"extension\":\"png\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":689876,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eMicroscopic appearance of comorbid pathology. (A–F) Case 1 diagnosed with Alzheimer’s disease. (A–C) Immunohistochemistry (IHC) for amyloid β (Aβ); (A) frontal cortex, (B) putamen, and (C) cerebellum. Widespread Aβ deposition is observed throughout the cerebrum, consistent with Thal phase 5. (D–F) IHC for phosphorylated tau (pTau); (D) Entorhinal region, (E) occipitotemporal gyrus, and (F) superior temporal gyrus show numerous neurofibrillary tangles (NFTs) and neuropil thread consistent with Braak NFT stage V. (G–I) Case 4 diagnosed with argyrophilic grain disease. (G) Hematoxylin and eosin (HE) staining of the amygdala shows moderate neuronal loss and gliosis. (H) Gallyas-Braak staining in the subiculum reveals numerous argyrophilic grains. (I) IHC for pTau of the amygdala demonstrates ballooned neurons. (J–L) Case 5 diagnosed with primary age-related tauopathy at Braak NFT stage III. (J) HE staining shows severe astrogliosis in the entorhinal cortex. (K) IHC for pTau shows numerous NFTs in the occipitotemporal cortex, with a density greater than that observed in the AD case. (L) IHC of the occipital cortex reveals no Aβ deposition. Bar = 100 μm (A–C, L), 50 μm (D–G, J–K), 20 μm (H–I).\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"2.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7559940/v1/491c1fb62949bcf275e69ab3.png\"},{\"id\":97723978,\"identity\":\"2b27d66e-e709-410c-9e5b-2eec06d88a32\",\"added_by\":\"auto\",\"created_at\":\"2025-12-08 16:10:27\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":1905994,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7559940/v1/a913a404-0790-4831-b1a7-4b89652e70d5.pdf\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"Contribution of Comorbid Pathologies to Amyotrophic Lateral Sclerosis with Cognitive or Behavioral Abnormalities\",\"fulltext\":[{\"header\":\"Background\",\"content\":\"\\u003cp\\u003eAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that affects the upper and lower motor neurons, leading to generalized muscle weakness and respiratory impairment [\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e]. Furthermore, cognitive or behavioral abnormalities occur in 30\\u0026ndash;50% of patients with ALS, and approximately 15% meet the diagnostic criteria for frontotemporal dementia [\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e]. The key pathological feature of ALS is the abnormal accumulation of TAR DNA-binding protein 43 (TDP-43) in the affected neurons [\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e] [\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e]. In patients with ALS and cognitive or behavioral abnormalities, TDP-43 pathology often extends beyond the motor neuron system into the frontotemporal lobe, overlapping with the pathological spectrum of frontotemporal lobar degeneration (FTLD) [\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e] [\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e]. TDP-43 pathology in the frontotemporal lobes is a major cause of cognitive or behavioral abnormalities in ALS. However, comorbid pathologies such as Alzheimer's disease (AD) also contribute to cognitive decline [\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e] [\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e]. The contribution of the comorbid pathology to ALS with cognitive or behavioral abnormalities remains unclear because postmortem examination is necessary for accurate diagnosis. Therefore, we aimed to clarify the contribution of comorbid pathologies to ALS with cognitive or behavioral abnormalities.\\u003c/p\\u003e\"},{\"header\":\"Methods\",\"content\":\"\\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003eSubjects\\u003c/h2\\u003e\\u003cp\\u003e\\u003cdiv class=\\\"BlockQuote\\\"\\u003e\\u003cp\\u003eWe screened the clinicopathological data of 153 consecutive autopsy cases of ALS from 2010 to 2023 at the Institute for Medical Science of Aging, Aichi Medical University. Of the 153 cases, 31 with clinically documented cognitive or behavioral abnormalities were included in this study. Two cases were excluded\\u0026mdash;one due to insufficient clinical data and tissue availability, and the other due to a preexisting self-directed personality. Thus, 29 cases were analyzed. All patients met the criteria for \\u0026ldquo;possible\\u0026rdquo; or more advanced categories according to the revised El Escorial criteria for ALS diagnosis [\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e]. Written informed consent was obtained from patients' relatives before the autopsy. The Research Ethics Committee of Aichi Medical University approved all investigations, which were conducted in accordance with all provisions of the Declaration of Helsinki.\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/p\\u003e\\u003c/div\\u003e\\n\\u003ch3\\u003eClinical assessments\\u003c/h3\\u003e\\n\\u003cp\\u003e\\u003cdiv class=\\\"BlockQuote\\\"\\u003e\\u003cp\\u003eWe retrospectively assessed clinical information from medical records and clinicopathological conferences, including age at death, sex, total disease duration, onset time of cognitive or behavioral abnormalities, and initial motor symptoms. The cognitive or behavioral abnormalities were classified based on the clinical descriptions. The cognitive abnormalities were categorized into the following domains: language dysfunction, executive dysfunction, and memory disturbance [\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e]. Language dysfunction included cases clinically diagnosed with progressive non-fluent aphasia or semantic dementia. Executive dysfunction was defined as impairment in executive functions, such as planning, judgment, problem-solving, cognitive flexibility, which significantly interfered with work or daily life activities. Memory impairment was defined as disturbance of short-term memory or episodic memory. Behavioral abnormalities include disinhibition, irritability, personality changes, apathy, altered food preferences, and perseverative behaviors.\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/p\\u003e\\n\\u003ch3\\u003eTissue preparation\\u003c/h3\\u003e\\n\\u003cp\\u003e\\u003cdiv class=\\\"BlockQuote\\\"\\u003e\\u003cp\\u003eThe left hemisphere of the brain and the spinal cord were fixed in 20% neutral-buffered formalin for at least 2 weeks. The left cerebral hemisphere was sectioned coronally at a thickness of 8 mm, the brainstem and spinal cord were sectioned transversely, and the cerebellum was sectioned sagittally at a thickness of 5 mm. Subsequently, the regions of interest were trimmed and embedded in paraffin. Sections of 9 \\u0026micro;m thickness were prepared for hematoxylin-eosin (HE), Kl\\u0026uuml;ver-Barrera, and Gallyas-Braak staining. Sections of 4.5 \\u0026micro;m thickness were prepared for immunohistochemical analysis. The primary antibodies used for immunohistochemistry were phosphorylated tau (1:4000, mouse monoclonal, clone AT-8; Thermo Scientific, Rockford, IL, USA), amyloid-β (1:1000, mouse monoclonal, clone 12B2; IBL, Gunma, Japan), phosphorylated α-synuclein (1:6000, mouse monoclonal, pSyn#64; Wako Pure Chemical Industries, Osaka, Japan), and phosphorylated TDP-43 (1:4000, rabbit polyclonal; Cosmo Bio, Tokyo, Japan).\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/p\\u003e\\n\\u003ch3\\u003eNeuropathological evaluation\\u003c/h3\\u003e\\n\\u003cp\\u003e\\u003cdiv class=\\\"BlockQuote\\\"\\u003e\\u003cp\\u003eThe pathological diagnosis of ALS was established based on neuronal loss and astrogliosis in the anterior horn of the spinal cord and the precentral gyrus in association with TDP-43 pathology (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003eA, B). We classified the cases into two subtypes (ALS types 1 and 2) based on their distribution pattern [\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e]. ALS type 1 is primarily localized to the motor neuron system, although a slight spread beyond the system occurs. ALS type 2 is characterized by the significant involvement of the frontotemporal cortex accompanied by cortical neuronal loss, astrogliosis, and microvacuolization (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003eC\\u0026ndash;E). Cortical TDP-43 pathology was classified into three subtypes according to the FTLD-TDP classification [\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e]. In addition, TDP-43 pathology was classified into five hierarchical stages based on previous reports [\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e] [\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e]. Hippocampal sclerosis (HS) in ALS was assessed based on neuronal loss and gliosis in the subiculum (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003eF) [\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e]. Comorbid pathology was assessed for AD, primary age-related tauopathy (PART), Lewy bodies disease (LBD), and argyrophilic grain disease (AGD). Neurofibrillary tangles (NFTs) were evaluated using Braak\\u0026rsquo;s stage [\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e]. Amyloid-β deposition was evaluated in five stages according to the Thal phase [\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e]. The density of the senile plaque was classified into four grades according to the consortium to establish a registry for Alzheimer\\u0026rsquo;s disease (CERAD) [\\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e]. The neuropathological diagnosis of AD was made for at least intermediate AD neuropathologic change, according to the National Institute on Aging-Alzheimer\\u0026rsquo;s Association criteria [\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e]. PART was assessed according to the proposed criteria by using Braak\\u0026rsquo;s NFT stage. NFTs at Braak Stage III or higher were considered to contribute to cognitive or behavioral abnormalities corresponding to senile dementia of neurofibrillary tangle-type (SD-NFT) [\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e] [\\u003cspan citationid=\\\"CR19\\\" class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e] [\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e]. LBD was screened by HE staining to identify Lewy bodies in the dorsal motor nucleus of the vagus, locus coeruleus, substantia nigra, and amygdala. α-Synuclein immunostaining was conducted in the dorsal motor nucleus and amygdala, and if positive, further staining of the brainstem, limbic regions, and cortex was performed according to the guidelines [\\u003cspan citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e]. AGD were categorized into three grades using Gallyas-Braak staining [\\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e].\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003c/p\\u003e\\n\\u003ch3\\u003eStatistical analyses\\u003c/h3\\u003e\\n\\u003cp\\u003e\\u003cdiv class=\\\"BlockQuote\\\"\\u003e\\u003cp\\u003eStatistical analyses were performed using R software (version 4.4.1; R Foundation for Statistical Computing, Vienna, Austria). The clinical and pathological findings were compared using the Mann\\u0026ndash;Whitney U and Fisher\\u0026rsquo;s exact tests for quantitative and qualitative variables, respectively. The significance level was set at 0.05 for comparisons between the two groups. All statistical analyses were two-sided.\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/p\\u003e\"},{\"header\":\"Results\",\"content\":\"\\u003cp\\u003eTable 1 compares the clinical and pathological features of ALS with and without comorbid pathologies. The study population was contained relatively older individuals, with a median age of 74 years, and included a slightly higher proportion of males. The median total duration was 40 months. In over 50% of the cases, cognitive or behavioral abnormalities appeared before the onset of motor symptoms. Notably, most initial motor symptoms began in the bulbar region. Behavioral abnormalities were the most common, observed in approximately 70% of the cases, followed by memory impairment in approximately 40%. Language impairment and executive dysfunction were observed in only a few cases. Approximately 80% of the cases were classified as ALS type 2. HS was observed in approximately 50% of the cases. Of the 29 cases, 17 had a comorbid pathology, such as AD, AGD, and PART, with Braak’s NFT stage Ⅲ. Four cases had a high-likelihood AD pathology, and five had an intermediate-likelihood AD pathology, totaling nine cases (Fig. 2A–F). AGD was diagnosed in four cases: two at stage I, and one each at stages II and III (Fig. 2G–I). Four cases of PART were classified as Braak’ NFT stage Ⅲ (Fig. 2J–L). None of the cases had α-synuclein pathology consistent with dementia with Lewy body, although one case showed a small number of α-synuclein positive structures in the medulla oblongata. The group with comorbid pathologies was significantly older than those without. The frequency of ALS type 2 was significantly higher in the group without comorbid pathology. No significant differences were observed between groups in sex distribution, disease duration, timing of dementia onset, initial motor symptoms (bulbar, upper limb, lower limb, respiratory muscles, or multiple regions), main cognitive symptoms (behavioral abnormalities, language impairment, executive dysfunction, or memory impairment), or the frequency of HS.\\u003c/p\\u003e\\n\\u003cp\\u003eTable 2 shows the clinicopathological profiles of the ALS cases with cognitive or behavioral abnormalities. All ALS type 1 cases exhibited comorbid pathology. Accordingly, the cases were classified into three groups based on the type of ALS and the presence of comorbid pathologies: ALS type 1 with comorbid pathology (Cases 1–6), ALS type 2 with comorbid pathology (Cases 7–17), and ALS type 2 without comorbid pathology (Cases 18–29). Behavioral abnormalities and memory impairment were present across all groups at a high frequency. In contrast, language impairment and executive dysfunction were observed only in cases with ALS type 2 pathology. Most ALS type 2 cases were classified as FTLD type B. HS was found in 14 out of the 23 ALS type 2 cases and was not observed in ALS type 1. Comorbid AD pathology was clinically suspected in three cases, with cognitive symptoms preceding the onset of motor symptoms. None of the patients had familial neurological disorders.\\u003c/p\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003e\\u003cdiv class=\\\"BlockQuote\\\"\\u003e\\u003cp\\u003eRepresentative cortical involvement in ALS includes neuronal loss, astrogliosis, and superficial spongiosis [\\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e]. Cognitive and behavioral abnormalities are significantly correlated with cortical TDP-43 pathology [\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e] [\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e] [\\u003cspan citationid=\\\"CR24\\\" class=\\\"CitationRef\\\"\\u003e24\\u003c/span\\u003e] [\\u003cspan citationid=\\\"CR25\\\" class=\\\"CitationRef\\\"\\u003e25\\u003c/span\\u003e]. In our cohort, 23 cases (79.3%) were classified as ALS type 2, with or without comorbid pathology. This finding suggests that most cognitive and behavioral abnormalities in ALS can be attributed to cortical involvement, which is consistent with previous reports. In contrast, six cases (20.7%) exhibited significant cognitive or behavioral abnormalities despite the absence of cortical TDP-43 pathology. This unexpected finding implies that additional pathological processes may underlie these symptoms. The overlap of neurodegenerative diseases is considered an important contributor to the heterogeneity of clinical symptoms [\\u003cspan citationid=\\\"CR26\\\" class=\\\"CitationRef\\\"\\u003e26\\u003c/span\\u003e]. Previous studies have reported that ALS is occasionally accompanied by additional neuropathological conditions, such as AD or LBD, which may complicate its clinical manifestations [\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR27\\\" class=\\\"CitationRef\\\"\\u003e27\\u003c/span\\u003e]. Hence, the presence of additional neuropathological findings, particularly in ALS type 1 cases, may reasonably be considered to contribute to cognitive or behavioral abnormalities in ALS. In this study, comorbid AD, AGD, and PART were identified in all six ALS cases without cortical involvement, suggesting their potential contribution to the observed cognitive and behavioral abnormalities.\\u003c/p\\u003e\\u003cp\\u003eAD may be the most notable neuropathological contributor to cognitive or behavioral abnormalities in ALS [\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e] [\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e]. Previous reports have described cases of high-likelihood AD pathology in the absence of cortical ALS involvement [\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e]. AD is the most common form of dementia and typically presents with memory impairment, although atypical clinical variants have also been described [\\u003cspan citationid=\\\"CR28\\\" class=\\\"CitationRef\\\"\\u003e28\\u003c/span\\u003e]. In our case series, AD-related pathology was observed in nine cases (Cases 1\\u0026ndash;3 and 7\\u0026ndash;12). Memory impairment was observed in three out of the four high-likelihood AD pathology cases, suggesting that AD pathology contributed to the observed symptoms. In addition, behavioral abnormalities with or without memory impairment were observed in approximately two-thirds of the cases with AD pathology. Behavioral abnormalities may appear to differ from the typical clinical presentation of AD; however, AD can also manifest with behavioral and psychological symptoms, which are described separately from cognitive decline and are referred to as behavioral and psychological symptoms of dementia (BPSD) [\\u003cspan citationid=\\\"CR29\\\" class=\\\"CitationRef\\\"\\u003e29\\u003c/span\\u003e]. The causes of BPSD are multifactorial, including environmental and physical factors. Notably, AD pathology has been linked to the emergence of BPSD even in the early stages of disease [\\u003cspan citationid=\\\"CR30\\\" class=\\\"CitationRef\\\"\\u003e30\\u003c/span\\u003e] [\\u003cspan citationid=\\\"CR31\\\" class=\\\"CitationRef\\\"\\u003e31\\u003c/span\\u003e]. Furthermore, in addition to physical disability, psychosocial stress and pain are common clinical issues in patients with ALS [\\u003cspan citationid=\\\"CR32\\\" class=\\\"CitationRef\\\"\\u003e32\\u003c/span\\u003e] [\\u003cspan citationid=\\\"CR33\\\" class=\\\"CitationRef\\\"\\u003e33\\u003c/span\\u003e]. These clinical factors increase the risk of BPSD [\\u003cspan citationid=\\\"CR34\\\" class=\\\"CitationRef\\\"\\u003e34\\u003c/span\\u003e]. In these present ALS cases showing behavioral abnormalities with comorbid AD pathology, the observed symptoms may have been driven by the AD pathology, a possibility that may be underrecognized and may complicate the clinical interpretation of behavioral abnormalities in ALS.\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/p\\u003e\\u003cp\\u003eWe found four (13.4%) cases with comorbid AGD pathology. ALS is sometimes accompanied by AGD [\\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e]. And its contribution to the clinical manifestation of ALS remains unclear because AGD can be present in older adults with preserved cognitive function [\\u003cspan citationid=\\\"CR35\\\" class=\\\"CitationRef\\\"\\u003e35\\u003c/span\\u003e]. However, AGD was first described as non-AD dementia, and cognitive symptoms appear to be associated with AGD, especially in the advanced stage [\\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e] [\\u003cspan citationid=\\\"CR36\\\" class=\\\"CitationRef\\\"\\u003e36\\u003c/span\\u003e]. In our series, only one case demonstrated AGD stage 3, and this case presented with memory impairment, which was consistent with the underlying pathology (Case 13). AGD has been associated with psychiatric symptoms [\\u003cspan citationid=\\\"CR36\\\" class=\\\"CitationRef\\\"\\u003e36\\u003c/span\\u003e] [\\u003cspan citationid=\\\"CR37\\\" class=\\\"CitationRef\\\"\\u003e37\\u003c/span\\u003e] [\\u003cspan citationid=\\\"CR38\\\" class=\\\"CitationRef\\\"\\u003e38\\u003c/span\\u003e], frequently with irritability [\\u003cspan citationid=\\\"CR36\\\" class=\\\"CitationRef\\\"\\u003e36\\u003c/span\\u003e]; bipolar disorder or late-onset schizophrenia [\\u003cspan citationid=\\\"CR37\\\" class=\\\"CitationRef\\\"\\u003e37\\u003c/span\\u003e] [\\u003cspan citationid=\\\"CR38\\\" class=\\\"CitationRef\\\"\\u003e38\\u003c/span\\u003e]; and psychiatric and cognitive symptoms, even at stage 2 or lower [\\u003cspan citationid=\\\"CR37\\\" class=\\\"CitationRef\\\"\\u003e37\\u003c/span\\u003e] [\\u003cspan citationid=\\\"CR39\\\" class=\\\"CitationRef\\\"\\u003e39\\u003c/span\\u003e]. Moreover, AGD is a risk factor for suicide regardless of the stage [\\u003cspan citationid=\\\"CR40\\\" class=\\\"CitationRef\\\"\\u003e40\\u003c/span\\u003e]. The amygdala is affected in the early stages of AGD, and the characteristic morphological features in this region include argyrophilic grains, ballooned neurons, granular fuzzy astrocytes, neuronal loss, and astrogliosis (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003eG\\u0026ndash;I) [\\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e]. The occurrence of psychotic symptoms in AGD cases may be associated with the initial involvement of the limbic system, such as the amygdala [\\u003cspan citationid=\\\"CR37\\\" class=\\\"CitationRef\\\"\\u003e37\\u003c/span\\u003e] [\\u003cspan citationid=\\\"CR40\\\" class=\\\"CitationRef\\\"\\u003e40\\u003c/span\\u003e]. Therefore, the development of behavioral abnormalities in the ALS type 1 cases with AGD stage 2 can be attributed to the underlying AGD pathology (Case 4).\\u003c/p\\u003e\\u003cp\\u003ePART is a pathological concept that describes limbic-predominant tau pathology in the absence of amyloid plaques, representing a continuum from cognitively normal aged individuals to those with dementia and encompasses SD-NFT [\\u003cspan citationid=\\\"CR19\\\" class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e]. Since PART is commonly identified at autopsy among elderly individuals without dementia, its contribution to cognitive symptoms should be interpreted carefully. SD-NFT is a form of dementia characterized by abundant NFTs in the limbic regions without amyloid-β deposition [\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e] [\\u003cspan citationid=\\\"CR41\\\" class=\\\"CitationRef\\\"\\u003e41\\u003c/span\\u003e]. Most patients diagnosed with SD-NFT are classified as NFT Braak stages III and IV [\\u003cspan citationid=\\\"CR42\\\" class=\\\"CitationRef\\\"\\u003e42\\u003c/span\\u003e] [\\u003cspan citationid=\\\"CR43\\\" class=\\\"CitationRef\\\"\\u003e43\\u003c/span\\u003e]. When comorbid pathology of PART NFT Braak stage III and IV is observed in autopsy cases of patients with dementia, its potential association with clinical dementia symptoms needs to be carefully considered as SD-NFT. The clinical presentation of SD-NFT resembles that of AD, and many cases are likely to be clinically misdiagnosed as AD unless confirmed by autopsy [\\u003cspan citationid=\\\"CR43\\\" class=\\\"CitationRef\\\"\\u003e43\\u003c/span\\u003e]. The progression of SD-NFT is generally slower than that of AD, and behavioral abnormalities emerge in the later stages of the disease [\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e] [\\u003cspan citationid=\\\"CR41\\\" class=\\\"CitationRef\\\"\\u003e41\\u003c/span\\u003e]. However, in psychiatric hospital cohorts, psychiatric symptoms, such as delusions, are common in SD-NFT, and the clinical manifestations observed in such cases may reflect the characteristics of the underlying cohort [\\u003cspan citationid=\\\"CR42\\\" class=\\\"CitationRef\\\"\\u003e42\\u003c/span\\u003e]. In our study, two ALS type 1 cases with PART, both classified as NFT Braak stage III, presented with behavioral abnormalities (Cases 5 and 6). A direct causal relationship cannot be established due to the mild degree of PART pathology and behavioral abnormalities are not specific symptom of SD-NFT. However, the presence of PART pathology in ALS type 1 cases with behavioral abnormalities suggests that its role in ALS should not be underestimated.\\u003c/p\\u003e\\u003cp\\u003eMemory impairment is not considered a specific cognitive symptom of ALS [\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e]. Initially, we hypothesized that memory impairment is significantly associated with comorbid pathologies. However, our results did not support this hypothesis, as approximately 40% of ALS type 2 cases without comorbid pathology exhibited memory impairment. Memory impairment is occasionally observed in patients with ALS and has been linked to hippocampal atrophy on neuroimaging [\\u003cspan citationid=\\\"CR44\\\" class=\\\"CitationRef\\\"\\u003e44\\u003c/span\\u003e] [\\u003cspan citationid=\\\"CR45\\\" class=\\\"CitationRef\\\"\\u003e45\\u003c/span\\u003e]. Advanced degeneration of the hippocampal perforant pathway, including the entorhinal region and subiculum in ALS, is associated with memory disturbances and mimics AD [\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e]. In this study, three of the five ALS type 2 cases without comorbid pathology or cases with memory impairment showed prominent HS (Cases 22, 23, and 28). These findings suggest that HS may contribute to memory impairment in ALS independent of comorbid pathologies. Thus, memory impairment did not reliably predict comorbid pathologies.\\u003c/p\\u003e\\u003cp\\u003eThe coexistence of ALS with Lewy body disease is rare but occasionally observed [\\u003cspan citationid=\\\"CR27\\\" class=\\\"CitationRef\\\"\\u003e27\\u003c/span\\u003e]. Previous reports have described ALS cases with α-synuclein pathology presenting with parkinsonism or orthostatic hypotension, suggesting that the comorbidity of α-synuclein pathology may influence the clinical manifestations of ALS[\\u003cspan citationid=\\\"CR27\\\" class=\\\"CitationRef\\\"\\u003e27\\u003c/span\\u003e] [\\u003cspan citationid=\\\"CR46\\\" class=\\\"CitationRef\\\"\\u003e46\\u003c/span\\u003e]. However, in the present study, only one case exhibited a small number of α-synuclein-positive structures in the medulla oblongata; this case was regarded as an incidental finding or prodromal Parkinson\\u0026rsquo;s disease, with little association with clinical symptoms.\\u003c/p\\u003e\\u003cp\\u003eThis study has some limitations. Whether these comorbid pathologies contribute to developing cognitive or behavioral symptoms remains a matter of discussion. The prevalence of comorbid pathology was significantly higher among older individuals. AD, AGD, and PART pathologies have also been observed in cognitively unimpaired older individuals [\\u003cspan citationid=\\\"CR47\\\" class=\\\"CitationRef\\\"\\u003e47\\u003c/span\\u003e]. Therefore, these pathologies may represent age-related changes rather than pathological contributors in older patients with ALS. The sample size was small, and further classification by ALS type and comorbid pathology led to even smaller subgroups, precluding meaningful subgroup analyses. Due to the retrospective nature of this study, causal relationships could not be established. Cognitive symptoms were assessed based on clinical descriptions rather than standardized neuropsychological testing, which may have introduced variability in interpretation and reduced objectivity. In addition, selection bias related to autopsy consent may have been present. Despite these limitations, our autopsy-based findings provide important insights into the potential contribution of comorbid pathologies to ALS with cognitive and behavioral abnormalities. To determine the contribution of comorbid pathologies to cognitive and behavioral abnormalities in ALS, prospective studies with larger cohorts, standardized cognitive assessments, and comparisons with appropriate control groups are needed.\\u003c/p\\u003e\"},{\"header\":\"Conclusion\",\"content\":\"\\u003cp\\u003eA high frequency of comorbid pathologies is observed in elderly patients with ALS with cognitive or behavioral abnormalities. There are cases of ALS in which comorbid pathologies such as AD, AGD, and PART may contribute to cognitive or behavioral abnormalities, even in the absence of cortical TDP-43 pathology. HS of ALS may contribute to memory impairment independently of comorbid pathologies. These findings highlight the clinicopathological complexity of cognitive and behavioral manifestations in ALS and emphasize the need for comprehensive pathological evaluation. In the clinical practice of the ALS with cognitive or behavioral abnormalities, such symptoms are typically attributed to cortical TDP-43 pathology; however, the contribution of comorbid pathologies should not be underestimated.\\u003c/p\\u003e\"},{\"header\":\"Abbreviations\",\"content\":\"\\u003cdiv class=\\\"DefinitionList\\\"\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eAD\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003eAlzheimer\\u0026rsquo;s disease\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eAGD\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003eargyrophilic grain disease\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eALS\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003eamyotrophic lateral sclerosis\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eBPSD\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003ebehavioral and psychological symptoms of dementia\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eDLB\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003edementia with Lewy bodies\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eCERAD\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003econsortium to establish a registry for Alzheimer\\u0026rsquo;s disease\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eFTLD\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003efrontotemporal lobar degeneration\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eHE\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003eHematoxylin and eosin\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eHS\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003ehippocampal sclerosis\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eIHC\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003eImmunohistochemistry\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eLBD\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003eLewy body disease\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eNA\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003enot available\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eNFT\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003eneurofibrillary tangle\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eNIA-AA\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003eNational Institute for Aging-Alzheimer Association\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003ePART\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003eprimary age-related tauopathy\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003epTau\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003ephosphorylated tau\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eTDP-43\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003etransactive response DNA-binding protein 43.\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eEthics approval and consent to participate\\u003cbr\\u003e\\u003c/strong\\u003eThe Research Ethics Committee of Aichi Medical University approved all investigations, which were conducted in accordance with all provisions of the Declaration of Helsinki. Written informed consent was obtained from patients' relatives before the autopsy.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConsent for publication\\u003cbr\\u003e\\u003c/strong\\u003eWritten informed consent was obtained from patients' relatives before the autopsy.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAvailability of data and materials\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe datasets used or analysed during the current study are available from the corresponding author on reasonable request.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCompeting interests\\u003cbr\\u003e\\u003c/strong\\u003eThe authors declare that they have no competing interests.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFunding\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis work was supported by AMED under Grant Number JP24wm0625301 (M.K.), MHLW Research on rare and intractable diseases Program Grant Number JPMH23FC1008(M.K.), and Grants-in-Aid from the Research Committee of CNS Degenerative Diseases, Research on Policy Planning and Evaluation for Rare and Intractable Diseases, Health, Labour and Welfare Sciences Research Grants, Ministry of Health, Labour and Welfare, Japan (Y. Iwasaki).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAuthors' contributions\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eHMo contributed to conceptualization, methodology, validation, formal analysis, investigation, resources, data curation, writing – original draft, and visualization. AA, YR, JS, HMi, and MY contributed to investigation and resources. MK contributed to conceptualization, methodology, supervision, and funding acquisition. YI contributed to conceptualization, methodology, validation, formal analysis, investigation, resources, data curation, writing – review \\u0026amp; editing, visualization, supervision, project administration, and funding acquisition. All authors read and approved the final manuscript.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eDeclaration of competing interest\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe authors declare no conflicts of interest.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgments\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eWe thank all\\u0026nbsp;patients,\\u0026nbsp;their families, and\\u0026nbsp;clinicians who referred patients to our institute. We also express our gratitude to Chizuko Sano, and Chieko Uno for their technical support during\\u0026nbsp;pathologic analyses.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\n\\u003cli\\u003eFeldman EL, Goutman SA, Petri S, Mazzini L, Savelieff MG, Shaw PJ, et al. Amyotrophic lateral sclerosis. Lancet. 2022;400:1363-80. doi: 10.1016/s0140-6736(22)01272-7.\\u003c/li\\u003e\\n\\u003cli\\u003eNeumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science. 2006;314:130-3. doi: 10.1126/science.1134108.\\u003c/li\\u003e\\n\\u003cli\\u003eArai T, Hasegawa M, Akiyama H, Ikeda K, Nonaka T, Mori H, et al. TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun. 2006;351:602-11. doi: 10.1016/j.bbrc.2006.10.093.\\u003c/li\\u003e\\n\\u003cli\\u003eNishihira Y, Tan CF, Onodera O, Toyoshima Y, Yamada M, Morita T, et al. Sporadic amyotrophic lateral sclerosis: two pathological patterns shown by analysis of distribution of TDP-43-immunoreactive neuronal and glial cytoplasmic inclusions. Acta Neuropathol. 2008;116:169-82. doi: 10.1007/s00401-008-0385-z.\\u003c/li\\u003e\\n\\u003cli\\u003eBrettschneider J, Libon DJ, Toledo JB, Xie SX, McCluskey L, Elman L, et al. Microglial activation and TDP-43 pathology correlate with executive dysfunction in amyotrophic lateral sclerosis. Acta Neuropathol. 2012;123:395-407. doi: 10.1007/s00401-011-0932-x.\\u003c/li\\u003e\\n\\u003cli\\u003eHamilton RL, Bowser R. Alzheimer disease pathology in amyotrophic lateral sclerosis. Acta Neuropathol. 2004;107:515-22. doi: 10.1007/s00401-004-0843-1.\\u003c/li\\u003e\\n\\u003cli\\u003eVerde F, Aiello EN, Adobbati L, Poletti B, Solca F, Tiloca C, et al. Coexistence of Amyotrophic Lateral Sclerosis and Alzheimer\\u0026apos;s Disease: Case Report and Review of the Literature. J Alzheimers Dis. 2023;95:1383-99. doi: 10.3233/jad-230562.\\u003c/li\\u003e\\n\\u003cli\\u003eBrooks BR, Miller RG, Swash M, Munsat TL. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord. 2000;1:293-9. doi: 10.1080/146608200300079536.\\u003c/li\\u003e\\n\\u003cli\\u003eStrong MJ, Abrahams S, Goldstein LH, Woolley S, McLaughlin P, Snowden J, et al. Amyotrophic lateral sclerosis - frontotemporal spectrum disorder (ALS-FTSD): Revised diagnostic criteria. Amyotroph Lateral Scler Frontotemporal Degener. 2017;18:153-74. doi: 10.1080/21678421.2016.1267768.\\u003c/li\\u003e\\n\\u003cli\\u003eMackenzie IR, Neumann M, Baborie A, Sampathu DM, Du Plessis D, Jaros E, et al. A harmonized classification system for FTLD-TDP pathology. Acta Neuropathol. 2011;122:111-3. doi: 10.1007/s00401-011-0845-8.\\u003c/li\\u003e\\n\\u003cli\\u003eBrettschneider J, Del Tredici K, Toledo JB, Robinson JL, Irwin DJ, Grossman M, et al. Stages of pTDP-43 pathology in amyotrophic lateral sclerosis. Ann Neurol. 2013;74:20-38. doi: 10.1002/ana.23937.\\u003c/li\\u003e\\n\\u003cli\\u003eBrettschneider J, Arai K, Del Tredici K, Toledo JB, Robinson JL, Lee EB, et al. TDP-43 pathology and neuronal loss in amyotrophic lateral sclerosis spinal cord. Acta Neuropathol. 2014;128:423-37. doi: 10.1007/s00401-014-1299-6.\\u003c/li\\u003e\\n\\u003cli\\u003eTakeda T, Uchihara T, Arai N, Mizutani T, Iwata M. Progression of hippocampal degeneration in amyotrophic lateral sclerosis with or without memory impairment: distinction from Alzheimer disease. Acta Neuropathol. 2009;117:35-44. doi: 10.1007/s00401-008-0447-2.\\u003c/li\\u003e\\n\\u003cli\\u003eBraak H, Alafuzoff I, Arzberger T, Kretzschmar H, Del Tredici K. Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol. 2006;112:389-404. doi: 10.1007/s00401-006-0127-z.\\u003c/li\\u003e\\n\\u003cli\\u003eThal DR, R\\u0026uuml;b U, Orantes M, Braak H. Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology. 2002;58:1791-800. doi: 10.1212/wnl.58.12.1791.\\u003c/li\\u003e\\n\\u003cli\\u003eMirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, et al. The Consortium to Establish a Registry for Alzheimer\\u0026apos;s Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer\\u0026apos;s disease. Neurology. 1991;41:479-86. doi: 10.1212/wnl.41.4.479.\\u003c/li\\u003e\\n\\u003cli\\u003eHyman BT, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Carrillo MC, et al. National Institute on Aging-Alzheimer\\u0026apos;s Association guidelines for the neuropathologic assessment of Alzheimer\\u0026apos;s disease. Alzheimers Dement. 2012;8:1-13. doi: 10.1016/j.jalz.2011.10.007.\\u003c/li\\u003e\\n\\u003cli\\u003eYamada M. Senile dementia of the neurofibrillary tangle type (tangle-only dementia): neuropathological criteria and clinical guidelines for diagnosis. Neuropathology. 2003;23:311-7. doi: 10.1046/j.1440-1789.2003.00522.x.\\u003c/li\\u003e\\n\\u003cli\\u003eCrary JF, Trojanowski JQ, Schneider JA, Abisambra JF, Abner EL, Alafuzoff I, et al. Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathol. 2014;128:755-66. doi: 10.1007/s00401-014-1349-0.\\u003c/li\\u003e\\n\\u003cli\\u003eJellinger KA, Alafuzoff I, Attems J, Beach TG, Cairns NJ, Crary JF, et al. PART, a distinct tauopathy, different from classical sporadic Alzheimer disease. Acta Neuropathol. 2015;129:757-62. doi: 10.1007/s00401-015-1407-2.\\u003c/li\\u003e\\n\\u003cli\\u003eMcKeith IG, Boeve BF, Dickson DW, Halliday G, Taylor JP, Weintraub D, et al. Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. Neurology. 2017;89:88-100. doi: 10.1212/wnl.0000000000004058.\\u003c/li\\u003e\\n\\u003cli\\u003eSaito Y, Ruberu NN, Sawabe M, Arai T, Tanaka N, Kakuta Y, et al. Staging of argyrophilic grains: an age-associated tauopathy. J Neuropathol Exp Neurol. 2004;63:911-8. doi: 10.1093/jnen/63.9.911.\\u003c/li\\u003e\\n\\u003cli\\u003eMitsuyama Y. Presenile dementia with motor neuron disease in Japan: clinico-pathological review of 26 cases. J Neurol Neurosurg Psychiatry. 1984;47:953-9. doi: 10.1136/jnnp.47.9.953.\\u003c/li\\u003e\\n\\u003cli\\u003eTakeuchi R, Tada M, Shiga A, Toyoshima Y, Konno T, Sato T, et al. Heterogeneity of cerebral TDP-43 pathology in sporadic amyotrophic lateral sclerosis: Evidence for clinico-pathologic subtypes. Acta Neuropathol Commun. 2016;4:61. doi: 10.1186/s40478-016-0335-2.\\u003c/li\\u003e\\n\\u003cli\\u003eSuzuki Y, Adachi T, Yoshida K, Sakuwa M, Hanajima R. Psychiatric symptoms and TDP-43 pathology in amyotrophic lateral sclerosis. J Neurol Sci. 2024;466:123249. doi: 10.1016/j.jns.2024.123249.\\u003c/li\\u003e\\n\\u003cli\\u003eArmstrong RA, Lantos PL, Cairns NJ. Overlap between neurodegenerative disorders. Neuropathology. 2005;25:111-24. doi: 10.1111/j.1440-1789.2005.00605.x.\\u003c/li\\u003e\\n\\u003cli\\u003eForrest SL, Kim JH, De Sousa C, Cheong R, Crockford DR, Sheedy D, et al. Coexisting Lewy body disease and clinical parkinsonism in amyotrophic lateral sclerosis. Eur J Neurol. 2021;28:2192-9. doi: 10.1111/ene.14849.\\u003c/li\\u003e\\n\\u003cli\\u003eScheltens P, De Strooper B, Kivipelto M, Holstege H, Ch\\u0026eacute;telat G, Teunissen CE, et al. Alzheimer\\u0026apos;s disease. Lancet. 2021;397:1577-90. doi: 10.1016/s0140-6736(20)32205-4.\\u003c/li\\u003e\\n\\u003cli\\u003eIsmail Z, Creese B, Aarsland D, Kales HC, Lyketsos CG, Sweet RA, et al. Psychosis in Alzheimer disease - mechanisms, genetics and therapeutic opportunities. Nat Rev Neurol. 2022;18:131-44, doi: 10.1038/s41582-021-00597-3.\\u003c/li\\u003e\\n\\u003cli\\u003eFarber NB, Rubin EH, Newcomer JW, Kinscherf DA, Miller JP, Morris JC, et al. Increased neocortical neurofibrillary tangle density in subjects with Alzheimer disease and psychosis. Arch Gen Psychiatry. 2000;57:1165-73. doi: 10.1001/archpsyc.57.12.1165.\\u003c/li\\u003e\\n\\u003cli\\u003eEhrenberg AJ, Suemoto CK, Fran\\u0026ccedil;a Resende EP, Petersen C, Leite REP, Rodriguez RD, et al. Neuropathologic Correlates of Psychiatric Symptoms in Alzheimer\\u0026apos;s Disease. J Alzheimers Dis. 2018;66:115-26. doi: 10.3233/jad-180688.\\u003c/li\\u003e\\n\\u003cli\\u003eFelgoise SH, Chakraborty BH, Bond E, Rodriguez J, Bremer BA, Walsh SM, et al. Psychological morbidity in ALS: the importance of psychological assessment beyond depression alone. Amyotroph Lateral Scler. 2010;11:351-8. doi: 10.3109/17482961003667630.\\u003c/li\\u003e\\n\\u003cli\\u003eChi\\u0026ograve; A, Mora G, Lauria G. Pain in amyotrophic lateral sclerosis. Lancet Neurol. 2017;16:144-57. doi: 10.1016/s1474-4422(16)30358-1.\\u003c/li\\u003e\\n\\u003cli\\u003eKales HC, Gitlin LN, Lyketsos CG. Assessment and management of behavioral and psychological symptoms of dementia. Bmj. 2015;350:h369. doi: 10.1136/bmj.h369.\\u003c/li\\u003e\\n\\u003cli\\u003eJosephs KA, Whitwell JL, Parisi JE, Knopman DS, Boeve BF, Geda YE, et al. Argyrophilic grains: a distinct disease or an additive pathology? Neurobiol Aging. 2008;29:566-73. doi: 10.1016/j.neurobiolaging.2006.10.032.\\u003c/li\\u003e\\n\\u003cli\\u003eTogo T, Isojima D, Akatsu H, Suzuki K, Uchikado H, Katsuse O, et al. Clinical features of argyrophilic grain disease: a retrospective survey of cases with neuropsychiatric symptoms. Am J Geriatr Psychiatry. 2005;13:1083-91. doi: 10.1176/appi.ajgp.13.12.1083.\\u003c/li\\u003e\\n\\u003cli\\u003eNagao S, Yokota O, Ikeda C, Takeda N, Ishizu H, Kuroda S, et al. Argyrophilic grain disease as a neurodegenerative substrate in late-onset schizophrenia and delusional disorders. Eur Arch Psychiatry Clin Neurosci. 2014;264:317-31. doi: 10.1007/s00406-013-0472-6.\\u003c/li\\u003e\\n\\u003cli\\u003eShioya A, Saito Y, Arima K, Kakuta Y, Yuzuriha T, Tanaka N, et al. Neurodegenerative changes in patients with clinical history of bipolar disorders. Neuropathology. 2015;35:245-53. doi: 10.1111/neup.12191.\\u003c/li\\u003e\\n\\u003cli\\u003eWurm R, Klotz S, Rahimi J, Katzenschlager R, Lindeck-Pozza E, Regelsberger G, et al. Argyrophilic grain disease in individuals younger than 75 years: clinical variability in an under-recognized limbic tauopathy. Eur J Neurol. 2020;27:1856-66. doi: 10.1111/ene.14321.\\u003c/li\\u003e\\n\\u003cli\\u003eYoshida K, Hata Y, Ichimata S, Okada K, Nishida N. Argyrophilic grain disease is common in older adults and may be a risk factor for suicide: a study of Japanese forensic autopsy cases. Transl Neurodegener. 2023;12:16. doi: 10.1186/s40035-023-00352-2.\\u003c/li\\u003e\\n\\u003cli\\u003eJellinger KA, Attems J. Neurofibrillary tangle-predominant dementia: comparison with classical Alzheimer disease. Acta Neuropathol. 2007;113:107-17. doi: 10.1007/s00401-006-0156-7.\\u003c/li\\u003e\\n\\u003cli\\u003eKawakami I, Hasegawa M, Arai T, Ikeda K, Oshima K, Niizato K, et al. Tau accumulation in the nucleus accumbens in tangle-predominant dementia. Acta Neuropathol Commun. 2014;2:40. doi: 10.1186/2051-5960-2-40.\\u003c/li\\u003e\\n\\u003cli\\u003eTahara N, Tahara D, Akagi A, Riku Y, Sone J, Miyahara H, et al. Hippocampal sclerosis in senile dementia of the neurofibrillary tangle type. J Neurol Sci. 2025;471:123437. doi: 10.1016/j.jns.2025.123437.\\u003c/li\\u003e\\n\\u003cli\\u003eAbdulla S, Machts J, Kaufmann J, Patrick K, Kollewe K, Dengler R, et al. Hippocampal degeneration in patients with amyotrophic lateral sclerosis. Neurobiol Aging. 2014;35:2639-45. doi: 10.1016/j.neurobiolaging.2014.05.035.\\u003c/li\\u003e\\n\\u003cli\\u003eRaaphorst J, van Tol MJ, de Visser M, van der Kooi AJ, Majoie CB, van den Berg LH, et al. Prose memory impairment in amyotrophic lateral sclerosis patients is related to hippocampus volume. Eur J Neurol. 2015;22:547-54. doi: 10.1111/ene.12615.\\u003c/li\\u003e\\n\\u003cli\\u003eYamada T, Itoh K, Matsuo K, Yamamoto Y, Hosokawa Y, Koizumi T, et al. Concomitant alpha-synuclein pathology in an autopsy case of amyotrophic lateral sclerosis presenting with orthostatic hypotension and cardiac arrests. Neuropathology. 2014;34:164-9. doi: 10.1111/neup.12057.\\u003c/li\\u003e\\n\\u003cli\\u003eKnopman DS, Parisi JE, Salviati A, Floriach-Robert M, Boeve BF, Ivnik RJ, et al. Neuropathology of cognitively normal elderly. J Neuropathol Exp Neurol. 2003;62:1087-95. doi: 10.1093/jnen/62.11.1087.\\u003c/li\\u003e\\n\\u003c/ol\\u003e\"},{\"header\":\"Tables\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eTable 1\\u0026nbsp;\\u003c/strong\\u003eComparison of clinical and pathological features between the\\u0026nbsp;amyotrophic lateral sclerosis (ALS) cases with or without comorbid pathology.\\u003c/p\\u003e\\n\\u003ctable border=\\\"0\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\" width=\\\"567\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 215px;\\\"\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003eTotal\\u0026nbsp;\\u003cbr\\u003e\\u0026nbsp;N=29\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003eComorbid pathology (-)\\u003cbr\\u003e\\u0026nbsp;N=12\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 92px;\\\"\\u003e\\n \\u003cp\\u003eComorbid pathology (+)\\u003cbr\\u003e\\u0026nbsp;N=17\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 66px;\\\"\\u003e\\n \\u003cp\\u003eP value\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003eAge at death (years)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e74 (68\\u0026ndash;79)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e68 (58\\u0026ndash;76)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 92px;\\\"\\u003e\\n \\u003cp\\u003e76 (71\\u0026ndash;79)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 66px;\\\"\\u003e\\n \\u003cp\\u003e0.048\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003eSex (male)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e19 (65)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e7 (58.3)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 92px;\\\"\\u003e\\n \\u003cp\\u003e12 (70.6)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 66px;\\\"\\u003e\\n \\u003cp\\u003e0.694\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003eTotal disease duration (months)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e40 (21.5\\u0026ndash;108.75)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e39 (22.5\\u0026ndash;87.5)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 92px;\\\"\\u003e\\n \\u003cp\\u003e47 (20\\u0026ndash;133)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 66px;\\\"\\u003e\\n \\u003cp\\u003e0.925\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003eOnset of cognitive or behavioral abnormality\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 92px;\\\"\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 66px;\\\"\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp; before motor symptom\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e15 (51.7)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e6 (50.0)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 92px;\\\"\\u003e\\n \\u003cp\\u003e9 (52.9)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 66px;\\\"\\u003e\\n \\u003cp\\u003e1.000\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp; after motor symptom\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e5 (17.2)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e2 (16.7)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 92px;\\\"\\u003e\\n \\u003cp\\u003e3 (17.6)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 66px;\\\"\\u003e\\n \\u003cp\\u003e1.000\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp; simultaneous\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e5 (17.2)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e1 (8.3)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 92px;\\\"\\u003e\\n \\u003cp\\u003e4 (23.5)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 66px;\\\"\\u003e\\n \\u003cp\\u003e0.370\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp; NA\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e4 (13.8)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e3 (25.0)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 92px;\\\"\\u003e\\n \\u003cp\\u003e1 (5.9)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 66px;\\\"\\u003e\\n \\u003cp\\u003e0.279\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003eInitial motor symptom\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 92px;\\\"\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 66px;\\\"\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp; bulbar\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e14 (48.3)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e5 (41.7)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 92px;\\\"\\u003e\\n \\u003cp\\u003e9 (52.9)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 66px;\\\"\\u003e\\n \\u003cp\\u003e0.710\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp; upper\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e6 (20.7)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e5 (41.7)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 92px;\\\"\\u003e\\n \\u003cp\\u003e1 (5.9)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 66px;\\\"\\u003e\\n \\u003cp\\u003e0.056\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp; lower\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e4 (13.8)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e1 (8.3)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 92px;\\\"\\u003e\\n \\u003cp\\u003e3 (17.6)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 66px;\\\"\\u003e\\n \\u003cp\\u003e0.622\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp; respiratory\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e1 (3.4)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 92px;\\\"\\u003e\\n \\u003cp\\u003e1 (5.9)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 66px;\\\"\\u003e\\n \\u003cp\\u003e1.000\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp; multiple domains\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e2 (6.9)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 92px;\\\"\\u003e\\n \\u003cp\\u003e2 (11.8)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 66px;\\\"\\u003e\\n \\u003cp\\u003e0.498\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp; NA\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e2 (6.9)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e1 (8.3)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 92px;\\\"\\u003e\\n \\u003cp\\u003e1 (5.9)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 66px;\\\"\\u003e\\n \\u003cp\\u003e1.000\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003eMain cognitive or behavioral symptom\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 92px;\\\"\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 66px;\\\"\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp; behavioral abnormality\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e20 (69.0)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e8 (66.7)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 92px;\\\"\\u003e\\n \\u003cp\\u003e12 (70.6)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 66px;\\\"\\u003e\\n \\u003cp\\u003e1.000\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp; language dysfunction\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e3 (10.3)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 92px;\\\"\\u003e\\n \\u003cp\\u003e3 (17.6)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 66px;\\\"\\u003e\\n \\u003cp\\u003e0.246\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp; executive dysfunction\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e2 (6.9)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e2 (16.7)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 92px;\\\"\\u003e\\n \\u003cp\\u003e0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 66px;\\\"\\u003e\\n \\u003cp\\u003e0.163\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp; memory impairment\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e11 (37.9)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e5 (41.7)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 92px;\\\"\\u003e\\n \\u003cp\\u003e7 (41.2)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 66px;\\\"\\u003e\\n \\u003cp\\u003e1.000\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003eALS type2 pathology\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e23 (79.3)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e12 (100)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 92px;\\\"\\u003e\\n \\u003cp\\u003e11 (64.7)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 66px;\\\"\\u003e\\n \\u003cp\\u003e0.028\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003eHippocampal sclerosis\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e14 (48.3)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e6 (50.0)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 92px;\\\"\\u003e\\n \\u003cp\\u003e8 (47.1)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 66px;\\\"\\u003e\\n \\u003cp\\u003e1.000\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003eComorbid pathology\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 92px;\\\"\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 66px;\\\"\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp; AD\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e9 (31.0)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 92px;\\\"\\u003e\\n \\u003cp\\u003e9 (52.9)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 66px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp; AGD\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e4 (13.8)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 92px;\\\"\\u003e\\n \\u003cp\\u003e4 (23.5)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 66px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 215px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp; PART (≧ Braak NFT stage Ⅲ)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e4 (13.8)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 97px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 92px;\\\"\\u003e\\n \\u003cp\\u003e4 (23.5)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 66px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp\\u003eValues are presented as n (%) or median (IQR). Statistical analysis was performed using the Mann\\u0026ndash;Whitney U test for age at death and disease duration, and Fisher\\u0026rsquo;s test for other variables.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eTable 2\\u0026nbsp;\\u003c/strong\\u003e\\u003cstrong\\u003eClinicopathological profile of ALS cases with cognitive or behavioral abnormalities.\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003ctable border=\\\"0\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\" width=\\\"726\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 23px;\\\"\\u003e\\n \\u003cp\\u003eCase\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eALS\\u003cbr\\u003e\\u0026nbsp;subtype\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003eComorbid\\u003cbr\\u003e\\u0026nbsp;pathology\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003eAge at\\u0026nbsp;\\u003cbr\\u003e\\u0026nbsp;death\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 18px;\\\"\\u003e\\n \\u003cp\\u003eSex\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 41px;\\\"\\u003e\\n \\u003cp\\u003eDisease\\u003cbr\\u003e\\u0026nbsp;duration\\u003cbr\\u003e\\u0026nbsp;(months)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd colspan=\\\"4\\\" style=\\\"width: 211px;\\\"\\u003e\\n \\u003cp\\u003eMain cognitive or behavioral symptoms\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 45px;\\\"\\u003e\\n \\u003cp\\u003eStage of\\u0026nbsp;\\u003cbr\\u003e\\u0026nbsp;TDP-43\\u003cbr\\u003e\\u0026nbsp;pathology\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eFTLD\\u0026nbsp;\\u003cbr\\u003e\\u0026nbsp;subtype\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 16px;\\\"\\u003e\\n \\u003cp\\u003eHS\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003eNFT\\u0026nbsp;\\u003cbr\\u003e\\u0026nbsp;Braak\\u003cbr\\u003e\\u0026nbsp;stage\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003eA\\u0026beta;\\u003cbr\\u003e\\u0026nbsp;Thal\\u003cbr\\u003e\\u0026nbsp;Phase\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 43px;\\\"\\u003e\\n \\u003cp\\u003esenile\\u003cbr\\u003e\\u0026nbsp;plaque\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 56px;\\\"\\u003e\\n \\u003cp\\u003eNIA-AA\\u003cbr\\u003e\\u0026nbsp;AD\\u003cbr\\u003e\\u0026nbsp;likelihood\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 29px;\\\"\\u003e\\n \\u003cp\\u003eAGD\\u003cbr\\u003e\\u0026nbsp;stage\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026alpha;-synuclein\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 55px;\\\"\\u003e\\n \\u003cp\\u003ebehavioral\\u003cbr\\u003e\\u0026nbsp;abnormality\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003elanguage\\u003cbr\\u003e\\u0026nbsp;dysfunction\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003eexecutive\\u0026nbsp;\\u003cbr\\u003e\\u0026nbsp;dysfunction\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 51px;\\\"\\u003e\\n \\u003cp\\u003ememory\\u003cbr\\u003e\\u0026nbsp;impairment\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 23px;\\\"\\u003e\\n \\u003cp\\u003e1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType 1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003eAD\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003e85\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 18px;\\\"\\u003e\\n \\u003cp\\u003eF\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 41px;\\\"\\u003e\\n \\u003cp\\u003e324\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 55px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 51px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 45px;\\\"\\u003e\\n \\u003cp\\u003e1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 16px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003eⅤ\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e5\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 43px;\\\"\\u003e\\n \\u003cp\\u003eFrequent\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 56px;\\\"\\u003e\\n \\u003cp\\u003eHigh\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 29px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 23px;\\\"\\u003e\\n \\u003cp\\u003e2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType 1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003eAD\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003e79\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 18px;\\\"\\u003e\\n \\u003cp\\u003eM\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 41px;\\\"\\u003e\\n \\u003cp\\u003e12\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 55px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 51px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 45px;\\\"\\u003e\\n \\u003cp\\u003e3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 16px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003eⅢ\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 43px;\\\"\\u003e\\n \\u003cp\\u003eModerate\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 56px;\\\"\\u003e\\n \\u003cp\\u003eIntermediate\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 29px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 23px;\\\"\\u003e\\n \\u003cp\\u003e3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType 1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003eAD\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003e79\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 18px;\\\"\\u003e\\n \\u003cp\\u003eM\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 41px;\\\"\\u003e\\n \\u003cp\\u003e20\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 55px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 51px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 45px;\\\"\\u003e\\n \\u003cp\\u003e2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 16px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003eⅢ\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 43px;\\\"\\u003e\\n \\u003cp\\u003eSparse\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 56px;\\\"\\u003e\\n \\u003cp\\u003eIntermediate\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 29px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003eBrainstem\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 23px;\\\"\\u003e\\n \\u003cp\\u003e4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType 1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003eAGD\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003e68\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 18px;\\\"\\u003e\\n \\u003cp\\u003eF\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 41px;\\\"\\u003e\\n \\u003cp\\u003e23\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 55px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 51px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 45px;\\\"\\u003e\\n \\u003cp\\u003e3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 16px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003eⅢ\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 43px;\\\"\\u003e\\n \\u003cp\\u003eSparse\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 56px;\\\"\\u003e\\n \\u003cp\\u003eNot\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 29px;\\\"\\u003e\\n \\u003cp\\u003e2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 23px;\\\"\\u003e\\n \\u003cp\\u003e5\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType 1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003ePART\\u003csup\\u003e※\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003e71\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 18px;\\\"\\u003e\\n \\u003cp\\u003eF\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 41px;\\\"\\u003e\\n \\u003cp\\u003e62\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 55px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 51px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 45px;\\\"\\u003e\\n \\u003cp\\u003e1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 16px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003eⅢ\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 43px;\\\"\\u003e\\n \\u003cp\\u003eNone\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 56px;\\\"\\u003e\\n \\u003cp\\u003eNot\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 29px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 23px;\\\"\\u003e\\n \\u003cp\\u003e6\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType 1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003ePART\\u003csup\\u003e※\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003e78\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 18px;\\\"\\u003e\\n \\u003cp\\u003eF\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 41px;\\\"\\u003e\\n \\u003cp\\u003e140\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 55px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 51px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 45px;\\\"\\u003e\\n \\u003cp\\u003e3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 16px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003eⅢ\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 43px;\\\"\\u003e\\n \\u003cp\\u003eNone\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 56px;\\\"\\u003e\\n \\u003cp\\u003eNot\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 29px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 23px;\\\"\\u003e\\n \\u003cp\\u003e7\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType 2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003eAD\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003e89\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 18px;\\\"\\u003e\\n \\u003cp\\u003eF\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 41px;\\\"\\u003e\\n \\u003cp\\u003e239\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 55px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 51px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 45px;\\\"\\u003e\\n \\u003cp\\u003e4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType B\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 16px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003eⅥ\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e5\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 43px;\\\"\\u003e\\n \\u003cp\\u003eModerate\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 56px;\\\"\\u003e\\n \\u003cp\\u003eHigh\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 29px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 23px;\\\"\\u003e\\n \\u003cp\\u003e8\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType 2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003eAD\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003e77\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 18px;\\\"\\u003e\\n \\u003cp\\u003eM\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 41px;\\\"\\u003e\\n \\u003cp\\u003e47\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 55px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 51px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 45px;\\\"\\u003e\\n \\u003cp\\u003e4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType B\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 16px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003eⅥ\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e5\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 43px;\\\"\\u003e\\n \\u003cp\\u003eModerate\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 56px;\\\"\\u003e\\n \\u003cp\\u003eHigh\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 29px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 23px;\\\"\\u003e\\n \\u003cp\\u003e9\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType 2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003eAD\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003e75\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 18px;\\\"\\u003e\\n \\u003cp\\u003eM\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 41px;\\\"\\u003e\\n \\u003cp\\u003e60\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 55px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 51px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 45px;\\\"\\u003e\\n \\u003cp\\u003e4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType B\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 16px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003eⅤ\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e5\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 43px;\\\"\\u003e\\n \\u003cp\\u003eFrequent\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 56px;\\\"\\u003e\\n \\u003cp\\u003eHigh\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 29px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 23px;\\\"\\u003e\\n \\u003cp\\u003e10\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType 2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003eAD\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003e85\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 18px;\\\"\\u003e\\n \\u003cp\\u003eM\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 41px;\\\"\\u003e\\n \\u003cp\\u003e6\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 55px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 51px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 45px;\\\"\\u003e\\n \\u003cp\\u003e4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType B\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 16px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003eⅢ\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 43px;\\\"\\u003e\\n \\u003cp\\u003eModerate\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 56px;\\\"\\u003e\\n \\u003cp\\u003eIntermediate\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 29px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 23px;\\\"\\u003e\\n \\u003cp\\u003e11\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType 2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003eAD\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003e74\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 18px;\\\"\\u003e\\n \\u003cp\\u003eM\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 41px;\\\"\\u003e\\n \\u003cp\\u003e23\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 55px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 51px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 45px;\\\"\\u003e\\n \\u003cp\\u003e5\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType B\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 16px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003eⅢ\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 43px;\\\"\\u003e\\n \\u003cp\\u003eSparse\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 56px;\\\"\\u003e\\n \\u003cp\\u003eIntermediate\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 29px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 23px;\\\"\\u003e\\n \\u003cp\\u003e12\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType 2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003eAD\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003e71\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 18px;\\\"\\u003e\\n \\u003cp\\u003eM\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 41px;\\\"\\u003e\\n \\u003cp\\u003e36\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 55px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 51px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 45px;\\\"\\u003e\\n \\u003cp\\u003e5\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType B\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 16px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003eⅢ\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e5\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 43px;\\\"\\u003e\\n \\u003cp\\u003eFrequent\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 56px;\\\"\\u003e\\n \\u003cp\\u003eIntermediate\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 29px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 23px;\\\"\\u003e\\n \\u003cp\\u003e13\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType 2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003eAGD\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003e76\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 18px;\\\"\\u003e\\n \\u003cp\\u003eM\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 41px;\\\"\\u003e\\n \\u003cp\\u003e4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 55px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 51px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 45px;\\\"\\u003e\\n \\u003cp\\u003e4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType B\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 16px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003eⅢ\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 43px;\\\"\\u003e\\n \\u003cp\\u003eNone\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 56px;\\\"\\u003e\\n \\u003cp\\u003eNot\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 29px;\\\"\\u003e\\n \\u003cp\\u003e3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 23px;\\\"\\u003e\\n \\u003cp\\u003e14\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType 2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003eAGD\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003e80\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 18px;\\\"\\u003e\\n \\u003cp\\u003eM\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 41px;\\\"\\u003e\\n \\u003cp\\u003e137\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 55px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 51px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 45px;\\\"\\u003e\\n \\u003cp\\u003e4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType B\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 16px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003eⅡ\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 43px;\\\"\\u003e\\n \\u003cp\\u003eNone\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 56px;\\\"\\u003e\\n \\u003cp\\u003eNot\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 29px;\\\"\\u003e\\n \\u003cp\\u003e1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 23px;\\\"\\u003e\\n \\u003cp\\u003e15\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType 2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003eAGD\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003e65\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 18px;\\\"\\u003e\\n \\u003cp\\u003eM\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 41px;\\\"\\u003e\\n \\u003cp\\u003e69\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 55px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 51px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 45px;\\\"\\u003e\\n \\u003cp\\u003e4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType B\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 16px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003eⅠ\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 43px;\\\"\\u003e\\n \\u003cp\\u003eSparse\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 56px;\\\"\\u003e\\n \\u003cp\\u003eLow\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 29px;\\\"\\u003e\\n \\u003cp\\u003e1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 23px;\\\"\\u003e\\n \\u003cp\\u003e16\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType 2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003ePART\\u003csup\\u003e※\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003e70\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 18px;\\\"\\u003e\\n \\u003cp\\u003eF\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 41px;\\\"\\u003e\\n \\u003cp\\u003e133\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 55px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 51px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 45px;\\\"\\u003e\\n \\u003cp\\u003e4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType B\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 16px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003eⅢ\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 43px;\\\"\\u003e\\n \\u003cp\\u003eNone\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 56px;\\\"\\u003e\\n \\u003cp\\u003eNot\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 29px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 23px;\\\"\\u003e\\n \\u003cp\\u003e17\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType 2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003ePART\\u003csup\\u003e※\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003e69\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 18px;\\\"\\u003e\\n \\u003cp\\u003eM\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 41px;\\\"\\u003e\\n \\u003cp\\u003e10\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 55px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 51px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 45px;\\\"\\u003e\\n \\u003cp\\u003e5\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType B\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 16px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003eⅢ\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 43px;\\\"\\u003e\\n \\u003cp\\u003eNone\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 56px;\\\"\\u003e\\n \\u003cp\\u003eLow\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 29px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp\\u003e\\u0026nbsp;※PART is described as a comorbid pathology with Braak NFT stage 3 or higher\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eTable2\\u003c/strong\\u003e (continued)\\u003c/p\\u003e\\n\\u003ctable border=\\\"0\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\" width=\\\"728\\\" class=\\\"fr-table-selection-hover\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 23px;\\\"\\u003e\\n \\u003cp\\u003eCase\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eALS\\u003cbr\\u003e\\u0026nbsp;subtype\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003eComorbid\\u003cbr\\u003e\\u0026nbsp;pathology\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003eAge at\\u0026nbsp;\\u003cbr\\u003e\\u0026nbsp;death\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 18px;\\\"\\u003e\\n \\u003cp\\u003eSex\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 41px;\\\"\\u003e\\n \\u003cp\\u003eDisease\\u003cbr\\u003e\\u0026nbsp;duration\\u003cbr\\u003e\\u0026nbsp;(months)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd colspan=\\\"4\\\" style=\\\"width: 211px;\\\"\\u003e\\n \\u003cp\\u003eMain cognitive or behavioral symptoms\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 45px;\\\"\\u003e\\n \\u003cp\\u003eStage of\\u0026nbsp;\\u003cbr\\u003e\\u0026nbsp;TDP-43\\u003cbr\\u003e\\u0026nbsp;pathology\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eFTLD\\u0026nbsp;\\u003cbr\\u003e\\u0026nbsp;subtype\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 16px;\\\"\\u003e\\n \\u003cp\\u003eHS\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003eNFT\\u0026nbsp;\\u003cbr\\u003e\\u0026nbsp;Braak\\u003cbr\\u003e\\u0026nbsp;stage\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003eA\\u0026beta;\\u003cbr\\u003e\\u0026nbsp;Thal\\u003cbr\\u003e\\u0026nbsp;Phase\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 63px;\\\"\\u003e\\n \\u003cp\\u003esenile\\u003cbr\\u003e\\u0026nbsp;plaque\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 56px;\\\"\\u003e\\n \\u003cp\\u003eNIA-AA\\u003cbr\\u003e\\u0026nbsp;AD\\u003cbr\\u003e\\u0026nbsp;likelihood\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 29px;\\\"\\u003e\\n \\u003cp\\u003eAGD\\u003cbr\\u003e\\u0026nbsp;stage\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"2\\\" style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026alpha;-synuclein\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 55px;\\\"\\u003e\\n \\u003cp\\u003ebehavioral\\u003cbr\\u003e\\u0026nbsp;abnormality\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003elanguage\\u003cbr\\u003e\\u0026nbsp;dysfunction\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003eexecutive\\u0026nbsp;\\u003cbr\\u003e\\u0026nbsp;dysfunction\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 51px;\\\"\\u003e\\n \\u003cp\\u003ememory\\u003cbr\\u003e\\u0026nbsp;impairment\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 23px;\\\"\\u003e\\n \\u003cp\\u003e18\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType 2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003e45\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 18px;\\\"\\u003e\\n \\u003cp\\u003eM\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 41px;\\\"\\u003e\\n \\u003cp\\u003e11\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 55px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 51px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 45px;\\\"\\u003e\\n \\u003cp\\u003e4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType B\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 16px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003eⅠ\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 63px;\\\"\\u003e\\n \\u003cp\\u003eNone\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 56px;\\\"\\u003e\\n \\u003cp\\u003eNot\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 29px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 23px;\\\"\\u003e\\n \\u003cp\\u003e19\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType 2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003e88\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 18px;\\\"\\u003e\\n \\u003cp\\u003eF\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 41px;\\\"\\u003e\\n \\u003cp\\u003e108\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 55px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 51px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 45px;\\\"\\u003e\\n \\u003cp\\u003e4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType B\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 16px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003eⅠ\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 63px;\\\"\\u003e\\n \\u003cp\\u003eModerate\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 56px;\\\"\\u003e\\n \\u003cp\\u003eLow\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 29px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 23px;\\\"\\u003e\\n \\u003cp\\u003e20\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType 2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003e68\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 18px;\\\"\\u003e\\n \\u003cp\\u003eM\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 41px;\\\"\\u003e\\n \\u003cp\\u003e23\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 55px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 51px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 45px;\\\"\\u003e\\n \\u003cp\\u003e4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType B\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 16px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003eⅠ\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 63px;\\\"\\u003e\\n \\u003cp\\u003eNone\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 56px;\\\"\\u003e\\n \\u003cp\\u003eNot\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 29px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 23px;\\\"\\u003e\\n \\u003cp\\u003e21\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType 2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003e68\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 18px;\\\"\\u003e\\n \\u003cp\\u003eF\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 41px;\\\"\\u003e\\n \\u003cp\\u003e19\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 55px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 51px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 45px;\\\"\\u003e\\n \\u003cp\\u003e4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType B\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 16px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003eⅠ\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 63px;\\\"\\u003e\\n \\u003cp\\u003eNone\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 56px;\\\"\\u003e\\n \\u003cp\\u003eNot\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 29px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 23px;\\\"\\u003e\\n \\u003cp\\u003e22\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType 2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003e79\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 18px;\\\"\\u003e\\n \\u003cp\\u003eM\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 41px;\\\"\\u003e\\n \\u003cp\\u003e111\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 55px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 51px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 45px;\\\"\\u003e\\n \\u003cp\\u003e4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType B\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 16px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003eⅡ\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 63px;\\\"\\u003e\\n \\u003cp\\u003eNone\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 56px;\\\"\\u003e\\n \\u003cp\\u003eNot\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 29px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 23px;\\\"\\u003e\\n \\u003cp\\u003e23\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType 2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003e58\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 18px;\\\"\\u003e\\n \\u003cp\\u003eF\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 41px;\\\"\\u003e\\n \\u003cp\\u003e22\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 55px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 51px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 45px;\\\"\\u003e\\n \\u003cp\\u003e4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType B\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 16px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003eⅡ\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 63px;\\\"\\u003e\\n \\u003cp\\u003eModerate\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 56px;\\\"\\u003e\\n \\u003cp\\u003eLow\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 29px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 23px;\\\"\\u003e\\n \\u003cp\\u003e24\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType 2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003e70\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 18px;\\\"\\u003e\\n \\u003cp\\u003eF\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 41px;\\\"\\u003e\\n \\u003cp\\u003e39\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 55px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 51px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 45px;\\\"\\u003e\\n \\u003cp\\u003e4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType B\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 16px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003eⅠ\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 63px;\\\"\\u003e\\n \\u003cp\\u003eNone\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 56px;\\\"\\u003e\\n \\u003cp\\u003eNot\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 29px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 23px;\\\"\\u003e\\n \\u003cp\\u003e25\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType 2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 46px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003e75\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 18px;\\\"\\u003e\\n \\u003cp\\u003eF\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 41px;\\\"\\u003e\\n \\u003cp\\u003eNA\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 55px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 51px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 45px;\\\"\\u003e\\n \\u003cp\\u003e4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 35px;\\\"\\u003e\\n \\u003cp\\u003eType B\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 16px;\\\"\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 28px;\\\"\\u003e\\n \\u003cp\\u003eⅠ\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 63px;\\\"\\u003e\\n \\u003cp\\u003eNone\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 56px;\\\"\\u003e\\n \\u003cp\\u003eNot\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 29px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 27px;\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e26\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eType 2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e83\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eM\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e156\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eType A\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eⅡ\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eNone\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eNot\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e27\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eType 2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e66\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eM\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e67\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eType A\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eⅡ\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eNone\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eNot\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e28\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eType 2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e58\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eM\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e29\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e5\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eType B\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eⅠ\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eNone\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eNot\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e29\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eType 2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e45\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eM\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e41\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e+\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e5\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eType B\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eⅠ\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eNone\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003eNot\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":false,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":true,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"bmc-neurology\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"nurl\",\"sideBox\":\"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)\",\"snPcode\":\"\",\"submissionUrl\":\"https://www.editorialmanager.com/nurl\",\"title\":\"BMC Neurology\",\"twitterHandle\":\"BMC_series\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC Series\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Amyotrophic lateral sclerosis, Alzheimer’s disease, Argyrophilic grain disease, Senile dementia of the neurofibrillary tangle type, Primary age-related tauopathy, Frontotemporal lobar degeneration\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-7559940/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-7559940/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003eBackground: Amyotrophic lateral sclerosis (ALS) often presents with cognitive or behavioral abnormalities. The cortical involvement of TAR DNA-binding protein-43 (TDP-43) pathology is considered a major cause of these abnormalities. However, the contribution of underlying comorbid pathologies remains unclear.\\u003c/p\\u003e\\n\\u003cp\\u003eMethods: We investigated the clinicopathological characteristics of 29 autopsy cases of ALS with cognitive or behavioral abnormalities and evaluated the association between clinical symptoms and comorbid pathologies such as Alzheimer’s disease (AD), argyrophilic grain disease (AGD), dementia with Lewy bodies (DLB), and primary age-related tauopathy (PART), as well as the presence of cortical TDP-43 pathology.\\u003c/p\\u003e\\n\\u003cp\\u003eResults: Of the 29 patients, 17 exhibited comorbid pathologies (AD, AGD, or PART), which may contribute to cognitive or behavioral abnormalities. None of the cases met the pathological criteria for DLB. The group with comorbid pathologies was significantly older, but clinical symptoms did not differ between the groups. Behavioral abnormalities and memory impairment were frequently observed in both groups. All six subjects without cortical TDP-43 pathology had comorbid pathologies, which had a notable effect on cognitive or behavioral abnormalities. Hippocampal sclerosis and memory impairment were observed in ALS cases without comorbid pathologies.\\u003c/p\\u003e\\n\\u003cp\\u003eConclusion: A high frequency of comorbid pathologies is observed in elderly patients with ALS presenting with cognitive or behavioral abnormalities. There are cases of ALS in which comorbid pathologies such as AD, AGD, and PART may contribute to cognitive or behavioral abnormalities, even in the absence of cortical TDP-43 pathology. Hippocampal sclerosis of ALS may contribute to memory impairment independently of comorbid pathologies.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Contribution of Comorbid Pathologies to Amyotrophic Lateral Sclerosis with Cognitive or Behavioral Abnormalities\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2025-09-30 10:57:15\",\"doi\":\"10.21203/rs.3.rs-7559940/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"decision\",\"content\":\"Revision requested\",\"date\":\"2025-10-14T11:38:11+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2025-10-05T23:22:54+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2025-09-29T09:34:54+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"265810176455390881228732832320278827485\",\"date\":\"2025-09-18T16:39:04+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"141299112795576652829868023989698103254\",\"date\":\"2025-09-18T16:08:22+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewersInvited\",\"content\":\"\",\"date\":\"2025-09-18T16:05:50+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvited\",\"content\":\"\",\"date\":\"2025-09-15T14:23:17+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorAssigned\",\"content\":\"\",\"date\":\"2025-09-08T11:41:52+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"checksComplete\",\"content\":\"\",\"date\":\"2025-09-08T11:40:34+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"submitted\",\"content\":\"BMC Neurology\",\"date\":\"2025-09-08T04:29:15+00:00\",\"index\":\"\",\"fulltext\":\"\"}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"bmc-neurology\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"nurl\",\"sideBox\":\"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)\",\"snPcode\":\"\",\"submissionUrl\":\"https://www.editorialmanager.com/nurl\",\"title\":\"BMC Neurology\",\"twitterHandle\":\"BMC_series\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC Series\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"67af323a-a6cf-4f21-90d0-34c4692df39d\",\"owner\":[],\"postedDate\":\"September 30th, 2025\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"published-in-journal\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2025-12-08T16:04:16+00:00\",\"versionOfRecord\":{\"articleIdentity\":\"rs-7559940\",\"link\":\"https://doi.org/10.1186/s12883-025-04556-z\",\"journal\":{\"identity\":\"bmc-neurology\",\"isVorOnly\":false,\"title\":\"BMC Neurology\"},\"publishedOn\":\"2025-12-03 15:58:19\",\"publishedOnDateReadable\":\"December 3rd, 2025\"},\"versionCreatedAt\":\"2025-09-30 10:57:15\",\"video\":\"\",\"vorDoi\":\"10.1186/s12883-025-04556-z\",\"vorDoiUrl\":\"https://doi.org/10.1186/s12883-025-04556-z\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-7559940\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-7559940\",\"identity\":\"rs-7559940\",\"version\":[\"v1\"]},\"buildId\":\"XKTyCvWXoU3ODBz1xrDgd\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}