Cognitive impairment in multiple system atrophy and spinocerebellar ataxias: A case series

Cognitive impairment in multiple system atrophy and spinocerebellar ataxias: A case series | 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 Cognitive impairment in multiple system atrophy and spinocerebellar ataxias: A case series Jing Zhao, Yunsi Yin, Haoxun Yang, Qi Qin This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4702221/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Multiple system atrophy (MSA) and spinocerebellar ataxias (SCAs) share similar clinical symptoms. Therefore, it is challenging to differentiate MSA and SCAs according to clinical symptoms, especially in the early stage. Currently, the diagnosis still relies on auxiliary inspection and genetic testing. The difference in cognitive symptoms between MSA and SCAs has not been fully investigated. Hence, the aim of this study was to analyze the differences in cognitive impairment between MSA and SCAs. Methods Five MSA patients and 5 patients with SCAs were recruited from the memory clinic of Xuanwu Hospital from March to September 2021. We collected detailed clinical information, imaging data, neuropsychological scales and genetic analysis of the patients. Then, we compared the differences in each cognitive domain between MSA and SCA patients. Results Comparison of SCA and MSA patients revealed that MSA patients had lower scores on the Clinical Dementia Rating Scale (CDR). There were no statistically significant group difference in global cognitive functioning, as indicated by Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. Conclusion Both MSA and SCAs present with cognitive impairment, but MSA presents more obvious symptom severity. multiple system atrophy (MSA) spinocerebellar ataxias (SCAs) cognitive impairment Figures Figure 1 Figure 2 1. INTRODUCTION Spinocerebellar ataxias (SCAs) are the most common subset of hereditary cerebellar ataxias[ 1 , 2 ]. They are a group of progressive neurodegenerative diseases that are transmitted through autosomal dominance[ 1 , 3 ]. Via pathological changes characterized by cerebellar degeneration, the disease can affect not only the cerebellum and its connections but also the brainstem and spinal cord[ 7 , 8 ]. Despite the existence of over 40 genetic subtypes of SCAs, progressive ataxia is still the predominant clinical manifestation[ 2 , 9 ]. In recent years, with advances in genetic testing, research has achieved clear gene localization for most SCA subtypes [ 9 ]. Each subtype is named using the same convention: SCA followed by a number[ 8 , 10 ]. For example, the SCA1, 2, 3, 6, and 7 types are caused by the gene amplification of CAG, which encodes polyglutamine. This results in the production of toxic polyglutamine proteins[ 8 ]. Some conventional mutations, including single nucleotide variants and small insertions or deletions, are also involved in the pathogenesis of hereditary ataxia[ 11 ]. Another neurodegenerative disorder, multiple system atrophy (MSA), is a sporadic synucleinopathic disease [ 4 ], characterized by an adult-onset, relentless progression, and fatal neurodegeneration [ 5 ]. MSA is clinically characterized by various combinations of parkinsonism with poor or no response to levodopa therapy, cerebellar ataxia, autonomic nervous system dysfunction and pyramidal symptoms[ 6 ]. Beyond its core clinical symptoms, MSA manifests with a number of nonmotor and motor features[ 5 ]. Based on the predominant motor symptomatology, MSA is divided into two types: cerebellar ataxia-predominant MSA (MSA-C) and parkinsonism-predominant MSA (MSA-P)[ 5 , 22 ]. The diagnosis of MSA mainly relies on medical history, a physical examination and magnetic resonance imaging (MRI)[ 22 ]. Clinical diagnosis of MSA is difficult due to the lack of definitive biomarkers and its wide clinical overlap with other neurodegenerative disorders, especially SCA subtypes. MSA and SCAs share similar manifestations, including ataxia and pyramidal and extrapyramidal signs. Both SCA and MSA patients can exhibit atrophy and signal intensity changes in the cerebellum and brain stem on MRI scans. Accurate diagnosis can help to determine the best clinical management approach and improve prognosis. For this reason, genetic testing for SCAs, including SCA1, 2, 3, 6, 17 and DRPLA, may be crucial in the differential diagnosis of MSA patients without a family history. However, genetic testing involves second-generation sequencing, such as WES and NGS panels, which is not only expensive but also difficult to extend in primary hospitals. Due to the aforementioned challenges of the current methods of diagnosis, researchers have paid more attention to the differences in the nonmotor clinical manifestations of MSA and SCA patients, especially cognitive function. Although dementia is an exclusion criterion for the diagnosis of MSA[ 23 , 24 ], recent research advances have revealed different degrees of cognitive impairment in most MSA patients[ 23 , 25 – 27 ]. Some studies have reported that prominent frontal involvement in MSA, as detected by functional and structural imaging, is related to cognitive dysfunction[ 26 ]. Other researchers have found that cognitive impairment in MSA patients is triggered by focal frontostriatal degeneration and is characterized by abnormalities in cortical and subcortical structures[ 28 , 29 ]. Similarly, cognitive impairment and even dementia have been described in many types of SCAs[ 30 – 32 ]. Functional imaging studies have shown cerebellar activation independent of motor control during executive or attentional tasks[ 33 – 35 ]. Some researchers have studied afferent and efferent connections of the cerebellum, particularly via corticopontocerebellar pathways, and their relationship with cortical association areas[ 31 ]. The ‘cerebellar cognitive affective syndrome’ was proposed[ 31 , 32 , 36 ]. Patients with cerebellar ataxia exhibit cognitive impairment when the sensorimotor CCAS is involved[ 31 , 32 , 36 ]. Here, we summarize 5 cases of MSA and 5 cases of SCAs confirmed by genetic testing among patients at the memory clinic of Xuanwu Hospital. We analyzed scores on various cognitive domains among the two patient groups and explored the damage to cognitive domains. 2. METHODS 2.1 Subjects Five MSA patients and five SCA patients were enrolled consecutively from the memory clinic of Capital Medical University, Xuanwu Hospital, from March to September 2021. All five MSA cases were diagnosed according to the diagnostic criteria. All SCA cases were confirmed by genetic testing. Cognitive performance was assessed by a battery of objective neuropsychological tests. The study was approved by the Ethics Committee of Xuanwu Hospital. Written informed consent was obtained from each subject or from his or her guardian. 2.2 Clinical assessment Detailed clinical data, including main complaint, current medical history, past medical history and family medical history, were obtained from each patient and their families. Physical and neurological examinations were performed by more than two neurologists. A battery of laboratory blood tests and cerebrospinal fluid (CSF) examinations was conducted to exclude metabolic, toxic, and inflammatory causes. All five MSA patients were determined by diagnostic criteria, and all five SCAs patients underwent genetic testing to confirm SCA and its type. All patients underwent magnetic resonance imaging. Brain MRI scans were carried out according to the routine clinical method by a GE Discovery MR750 3.0T scanner. Conventional scanning sequences included T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), DWI, and fluid-attenuated inversion recovery (FLAIR). The extent of medial temporal atrophy (MTA) visible on MRI scans was assessed by visual rating scales as described previously. 2.3 Cognitive function assessment All patients completed a battery of neuropsychological tests, including the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Clinical Dementia Rating Scale (CDR), Frontal Assessment Battery (FAB), Clock Drawing Test (CDT), Trail Making Test (TMT), Auditory Verbal Learning Test (AVLT), Boston Naming Test (BNT), Neuropsychiatric Inventory Questionnaire (NPI), Geriatric Depression Scale (GDS), and Activities of Daily Living Scale (ADL). Global cognition was evaluated in terms of MMSE, MoCA, and CDR scores. Attention and executive function were measured by the TMT-A, TMT-B, CDT and FAB; memory function was measured by the AVLT-Immediate Recall and AVLT-Delayed Recall scores; language was measured by the BNT and Animal Fluency score of the MoCA; and visuospatial abilities were measured by the Pentagon Copying score in the MMSE and the Cube Copying score in the MoCA. The associations between cognitive impairment (test scores) and imaging lesions were evaluated by Spearman correlation analyses. 2.4 Statistical Analysis All statistical analyses were performed using the Statistical Package for Social Sciences (SPSS) for Windows, version V22.0 (IBM Corp., Armonk, NY). Descriptive statistics are presented in figures, means, standard deviations, and 95% confidence intervals. The analysis of patients involved the entire clinical sample. The MMSE, MoCA, ADL, CDR, CDR-SB, TMT-A, and TMT-B scores of MSA and SCA patients were compared using paired t tests. We then analyzed the differences in each cognitive domain among MSA, SCA and EOAD patients with Bonferroni and SNK-q tests. 3. RESULTS 3.1 Clinical manifestations In the table, we provide a detailed summary of the medical history and neurological examinations of MSA and SCA patients. MSA patients experienced adult onset and had no family history of MSA. SCA patients also had adult onset; 3 patients had a family history of SCA, and 1 patient had SCA confirmed by genetic diagnosis. The sex ratio (males/females) of the MSA and SCA groups was 3:2. The educational attainment of both groups was 6 years or above. The duration of cognitive impairment was more than 1 year. All clinical characteristics of the two groups of patients are summarized in Table 1 . Table 1 Demographic and clinical characteristics of patients in the 3 groups MSA SCA EOAD Patient number 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 6 Sex (male = 0, female = 1) 0 0 1 0 1 0 1 0 0 1 0 0 1 1 1 1 Onset age (years) 44 54 52 60 59 38 64 49 32 51 33 42 46 56 54 49 Educational attainment (years) 10 14 9 8 7 12 6 12 9 9 - - - - - - Cardiovascular history + - + + + - - - - - - - - - - - Hypertension + - - + - + - + - - - - - - - - Hyperlipidemia - - - - - + - - - - - - - - - - Diabetes - - - - - + - - - - - - - - - - Cognitive impairment duration (years) 3 1 6 1 6 2 1 3 1 1 1 2 5 3 3 1 Cognitive impairment Memory impairment - + - - - - + - - - + + + + + - Executive impairment + + - + + + + + + + - + + + - + Calculation impairment - + - - - - + - - - - - - - - - Visuospatial impairment - + + - - - + - - - - - - - - + Aphasia + - - - + - + - - - - + + - + - Other neurological presentation - - - - dysosmia tremor - dizziness - - - - - - - - Depression or anxiety history - - anxiety depression - - - - - - depression depression depression - anxiety - Relevant family history - - - - - + - + + - - - - - + - 3.2 Cognitive impairment To evaluate the overall cognitive function and cognitive status of patients, we used a series of neuropsychological scales. All patients were found to exhibit cognitive impairment and dementia. The mean MMSE scores of MSA and SCA patients were 21/30 and 21.7/30, respectively. The mean MoCA scores of MSA and SCA patients were 14.8/30 and 14.5/30, respectively. None of the patients exhibited normal cognitive function on the MoCA (scores ≥ 24). Outliers of TMT-A, TMT-B, and CDT scores confirmed the impairments in attention and executive function in patients with both disorders. Both groups had decreased ADL scores indicating significantly decreased activities of daily living. Except for two patients with SCA, the CDR scores reached a level of suspected dementia and above. In addition, we found 2 MSA patients (2/7, 40%) and 1 SCA patient (1.5, 20%) with abnormally high GDS scores. Except for 1 SCA patient, all patients exhibited abnormal NPI scores. This suggests that behavioral and psychological disorders are also common in these two diseases, which should be given more attention. We compared the scores on each cognitive domain between the MSA and SCA groups ( Fig. 1 ) . The results showed that there was no significant difference in MMSE (p = 0.59), MoCA (p = 0.87), CDT (p = 0.60), TMT-A (p = 0.65), TMT-B (p = 0.24), NPI (p = 0.38) or GDS (p = 0.2) scores. There was a difference in the overall CDR score (p = 0.048) between the two diseases, which suggests that although cognitive impairment appears in both diseases, it differs in severity; more MSA patients suffered from cognitive impairment. In addition, we included 5 patients with EOAD diagnosed by genetic testing from Xuanwu Hospital. Comparison of neuropsychological scores among MSA, SCA and EOAD (a traditional cognitive impairment) patients revealed further differences. Significant differences arose between MSA and EOAD patients as well as SCA and EOAD patients, in ADL, CDR domain, and overall CDR scores. Thus, in terms of impairment in activities of daily living and cognition, EOAD patients suffered to a greater extent than MSA and SCA patients.All cognitive domains scores of the three groups of patients are summarized in Table 2 . Table 2 Neuropsychological assessments of patients MSA SCA EOAD Patient number 1 2 3 4 5 1 2 3 4 5 6 1 2 3 4 5 6 MMSE score 23 19 23 22 18 22 20 24 20 21 23 13 27 14 12 23 13 MoCA score 16 14 20 11 13 14 13 14 14 19 13 6 25 8 7 13 7 CDT (0–15) 13 7 13 8 7 5 15 11 7 15 12 NA NA NA NA NA NA CDT (0–3) 2 1 2 2 1 1 1 2 1 3 2 0 2 0 0 1 2 ADL score 23 21 20 28 19 30 20 21 20 20 21 NA 27 35 27 23 31 CDR domain score 2.5 2 1 4.5 2 2.5 0 2 1 0 1.5 NA 3 11 4.5 4.5 8 CDR total score 0.5 0.5 0.5 1 1 0.5 0 0.5 0.5 0 0.5 NA 0.5 2 1 1 2 HIS score 0 1 9 2 1 4 1 4 1 5 1 NA NA NA NA NA NA TMT-A (s) 109 121 89.3 150.2 141 150 72.7 140.5 113 47.3 147 NA 75 150 66 64 150 TMT-B (s) 130 300 118.9 300 279 300 126.6 167.2 126 86.9 170 NA 156 300 150 96 200 NPI patient score 1 3 3 6 2 12 10 1 0 10 0 NA 6 0 5 11 1 NPI family score 1 2 0 0 2 2 1 0 1 1 1 NA 4 0 1 5 1 GDS score 4 11 10 7 11 5 0 4 12 6 8 NA 5 3 5 17 14 3.3 Imaging results Varying extents of brainstem and cerebellar atrophy were found in both MSA and SCA patients by cranial magnetic resonance imaging ( Fig. 2 ) . The coronal MRI of both patients did not show obvious atrophy of the hippocampus, and the imaging findings were consistent with clinical manifestations, which were in line with the characteristics of the diseases. There was no significant difference in the cranial magnetic resonance imaging findings between the two groups. These findings did not explain whether the degrees of cerebellar or brainstem atrophy were related to cognitive function (e.g., MMSE and MoCA scores). In the future, we hope to recruit more MSA and SCA patients and collect additional imaging data. Objective imaging indicators were included in a detailed quantitative analysis of brainstem volume, total cerebellum volume, total cerebellar gray matter volume, and white matter volume. We aim to collect more sensitive morphometric or functional magnetic resonance imaging data to observe the correlation between cerebellar and brainstem volume and cognitive impairment in these two disorders, to determine if there is a significant difference between them. 4. DISCUSSION Currently, the two most prevalent neurodegenerative diseases that can result in ataxia are MSA and SCAs. They are mostly diagnosed based on clinical symptoms, characteristic imaging findings, laboratory examinations, relevant family history and genetic testing. The current diagnosis of these diseases focuses more on movement disorders and abnormal autonomic function, while few summaries or related reports on the characteristics of cognitive function have been published. To our knowledge, no studies have compared the domain-specific characteristics of cognitive impairment between these diseases; thus, our work is groundbreaking as well as innovative. We recruited five patients with SCA confirmed by genome-wide analysis and 5 patients clinically diagnosed with MSA. We conducted a series of neuropsychological assessments to evaluate patients' overall cognitive function, numeracy, executive function, language, visuospatial abilities, and disease severity. Statistical analysis was used to investigate whether MSA and SCA patients differed in each cognitive domain. The results showed that the two groups significantly differed in CDR scores but not in MMSE/MoCA, CDT, TMT, AVLT, BNT, or Cube Copying scores. This result indicated that both MSA and SCA patients exhibited impairments in overall cognitive function, executive function and activities of daily living. Statistical analysis showed significant group differences in CDR scores but not in MMSE/MoCA, CDT, TMT, AVLT, BNT, or Cube Copying scores. Thus, we believe that both MSA and SCA are clinically characterized by damage to multiple systems that may cause cognitive impairment. The two groups had no significant differences in overall cognitive function, computing power, executive function, language, or visuospatial abilities, although they significantly differed in the severity of cognitive impairment. Specifically, MSA patients exhibited greater cognitive impairment than SCA patients. Thus, our study demonstrates that it is difficult to distinguish these two diseases based on cognitive function characteristics. Although both MSA and SCA are clinically characterized by damage to multiple systems and may cause cognitive impairment, MSA patients exhibited more severe cognitive impairment than SCA patients. The results of this study align with the characteristics of cognitive impairment reported in previous studies. In the MSA consensuses of 1999 and 2000, cognitive impairment was considered a warning sign of MSA diagnosis[ 5 , 21 – 24 , 27 ]. With recent research advances, increasing evidence has shown that MSA patients exhibit different degrees of cognitive impairment[ 6 , 21 , 23 , 26 , 27 ] and that approximately 20–30% of MSA patients suffer cognitive impairment[ 37 – 39 ]. This suggests that cognitive impairment can be used as a differential diagnosis for MSA and other neurodegenerative diseases. Some studies have suggested that localized frontostriatal degeneration induces cognitive impairment in MSA patients, characterized by abnormalities in cortical and subcortical structures[ 26 , 28 , 29 ]. This impairment is mainly manifested in executive function, memory, language and visuospatial abilities[ 6 , 23 , 26 , 28 ]. Moreover, a study by the Neuroscience Working Group of the MDS-MSA research group found that cognitive impairment in MSA patients was most prominent in executive function and verbal fluency, followed by attention, memory, and visuospatial abilities[ 27 , 40 ]. The degree of cognitive impairment in MSA patients was similar to that in patients with Parkinson's disease and less severe than that in patients with progressive supranuclear palsy[ 27 , 39 , 41 ]. The incidence of cognitive impairment gradually increases with the duration of the disease and worsens with its progression[ 27 , 28 , 38 ]. These studies all support our conclusions that both diseases may cause cognitive impairment and that MSA patients exhibit more severe cognitive impairment. In addition, we compared MSA and SCA patients and expanded the cognitive impairment characteristics for their diagnosis. SCAs, a type of neurodegenerative disease with ataxia as the main manifestation, can also cause cognitive dysfunction[ 7 , 30 – 32 , 36 ]. The conventional view is that the cerebellum is involved in motor control and assists in the completion of movement. [ 7 , 30 , 31 ]. As early as 1970, clinical and experimental data suggested the involvement of the cerebellum in the regulation of nonmotor functions[ 31 ]. Many researchers have examined the contribution to cognitive function of the cerebellum[ 31 ]. Among them, Schmahmann and Sherman reported that patients with congenital or acquired cerebellar disease are more prone to a range of cognitive impairments, exhibiting widespread executive dysfunction, including deficits in planning, set-shifting, abstract reasoning, spatial cognition (including visuospatial memory) and verbal fluency. Individuals also undergo personality changes characterized by inappropriate and childlike behaviors and flattened affect. Linguistic difficulties include dysfunction in naming, grammar and prosody. Schmahmann and Sherman termed this constellation of cognitive impairments cerebellar cognitive affective syndrome (CCAS) and suggested that it may be the result of disruptions to the cerebrocerebellar circuitry[ 7 , 31 , 36 ]. The mechanism underlying cognitive impairment in patients with SCAs has not been fully elucidated[ 30 , 36 ]. The frequencies of different subtypes of cognitive impairment also differ[ 31 , 36 ]. Previous studies have suggested that cognitive deficits in SCA1 and SCA3 are mainly manifested in attention, visuospatial perception, executive function, language fluency, immediate memory and long-term memory[ 7 , 30 ]. Approximately 5–25% of patients with advanced SCA1 exhibit cognitive impairment[ 30 ]. Burke et al. found that SCA1 patients have significant executive function deficits, and other studies have reported that this dysfunction is more prominent than that in the control group and other SCA subtypes[ 36 ]. A persistent feature of SCA3 is the presence of deficits in executive function and visuospatial abilities[ 31 ]. Both SCA1 and SCA3 patients may exhibit language and memory impairment[ 7 , 30 , 35 ]. In conclusion, each subtype of SCA has its own characteristic cognitive impairment. In-depth study of the characteristics of each subtype of cognitive impairment can help to improve disease management and patient quality of life[ 31 ]. Moreover, these same characteristics can be used as predictors of disease. However, the mechanism underlying cognitive impairment in SCA patients has not been fully elucidated. The frequency of different cognitive impairments also varies. Cognitive impairment was observed in SCA1, 2, 3, 6, 7, 8, 10, 12, 17, 19, 21, and DRPLA, while dementia was reported in SCA2, 3, 8, 12, 19, and DRPLA. Cognitive impairment can also occur in patients with SCA13[ 7 ]. Moreover, we revealed that genotyping was still the key method of distinguishing MSA and SCA. Five SCA patients included in our study were diagnosed with SCA1 and SCA3 by genetic diagnosis. The neuropsychological scores showed varying degrees of cognitive impairment. SCAs are a group of highly heterogeneous inherited neurodegenerative diseases with complex genetic and phenotypic features[ 1 , 9 ]. Among them, SCA1, 2, 3, 6, 7, etc., are caused by amplification and unstable polymorphism in the coding region of the gene and the mutation of the trinucleotide CAG repeat sequence. The product of this gene is a protein called ataxin. This mutated protein has toxic effects that can lead to degeneration of neural function[ 8 ]. The cognitive function of EOAD patients and SCA patients were compared, and we found that there were differences in ADL, CDR domain and CDR total scores between SCA and EOAD patients. These differences in cognitive impairment may be due to the different pathophysiological mechanisms. These findings may inform differential diagnosis at the cognitive level in clinical work. The most common neurodegenerative disease, AD, often occurs in elderly individuals. However, approximately 4–5% of patients develop early-onset Alzheimer's disease (EOAD) before the age of 65 years[ 42 , 43 ]. Most EOAD cases are sporadic, but approximately 5% are due to autosomal dominant inheritance. Amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) are the most common mutations in EOAD and can lead to the overproduction and deposition of amyloid beta, neuronal degeneration and eventually dementia[ 43 ]. Another important theory is that the hyperphosphorylated tau protein affects the stability of the neuronal cytoskeleton tubulin, resulting in neurofibrillary tangles that damage the function of neurons and eventually lead to cognitive impairment[ 43 ]. The pathophysiological mechanism underlying SCA-induced cognitive impairment has not been fully elucidated. Some studies have suggested that it is caused by the disruption of cerebellar circuits at different levels of the central nervous system. In 1991, Schmahmann proposed that the cerebellum is involved in higher cortical functions after studying the afferent and efferent connections of the cerebellum, particularly the corticopontocerebellar pathway[ 31 ]. In 1997, Schmahmann and Sherman proposed the cerebellar cognitive affective syndrome. These functional deficits are thought to result from a disruption of pathways connecting the cerebellum to the prefrontal, posterior parietal, superior temporal, and limbic areas. Neuroimaging, neuropsychological, and neuroanatomical data suggest that the cerebellum contributes to executive control. Neuroimaging studies have demonstrated cortical damage, white matter involvement, cerebral hypoperfusion, and hypometabolism in SCA patients. However, how these impairments relate to cognitive function is unclear. By assessing the correlations of cognitive function with brain atrophy, cerebral perfusion, and metabolism, mechanisms underlying cognitive impairment may be revealed. Our study has a few limitations. First, the sample size was relatively small. Nevertheless, a series of well-established neuropsychological assessments detected difference between the two diseases, suggesting that we should devote more attention to the cognitive characteristics of these two diseases. Second, we included only cross-sectional data in this study. In the future, we will carry out a larger-scale cohort study to further analyze the characteristics of impairment in each cognitive domain of MSA and SCA patients. Clinical management of patients in later stages and rehabilitation training benefit from the identification and analysis of these diseases at the cognitive level, which can delay their progression. 5. CONCLUSION By summarizing and comparing the clinical history and neuropsychological scores of patients with MSA and SCA, we hoped to better distinguish these two common neurodegenerative diseases that clinically manifest mainly as movement disorders. We first assessed the characteristics of cognitive impairment in these two diseases. We found that, consistent with previous research, both disorders showed varying degrees of cognitive impairment, including impairment of overall cognitive function, attention, and executive function. Both MSA and SCA decreased the ability to perform activities of daily living. Statistical analysis revealed a difference in the severity of cognitive impairment, with MSA patients experiencing more severe impairment. Finally, we found it difficult to distinguish between these two diseases in terms of cognitive function; thus, further in-depth and large-scale studies are needed. Genetic diagnosis remains critical for differentiating the two diseases. This study provides preliminary findings regarding the use of cognitive impairment to distinguish the two diseases as well as clues for differential diagnosis. Declarations Acknowledgments The authors declare that they have no conflicts of interest. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee as well as those of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Authors’ contributions Zhao.J. analysed data, drafted and revised the manuscript. Yin.Y.S. performed data collection, followed patients and revised manuscript. Yang.H.X. performed stastical analysis, data interpretation. Qin.Q. designed the study, analysed data, drafted and revised the manuscript. All authors read and approved the final manuscript. Funding The work was supported by Young Elite Scientists Sponsorship Program by CAST (2021QNRC001), Beijing Hospitals Authority Innovation Studio of Young Staff Funding Support (202118), Beijing Nova Program (Z211100002121051), National Natural Science Foundation of China (82201568). Availablility of data and materials The datasets generated and/or analysed during the current study are not publicly available due to privacy or ethical restrictions. But are available from the corresponding author on reasonable request. Ethics approval and consent to participate All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study has been approved by the Ethics Committee of Xuan Wu Hospital,Capital Medical University,Beijing,China. Written informed consent has been obtained from all patients or their legal surrogates, and all patients had approved the reuse of their medical records. Consent for publication All the authors consented for publication. 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Koga, S., et al., Profile of cognitive impairment and underlying pathology in multiple system atrophy. Mov Disord, 2017. 32 (3): p. 405-413. Cao, B., et al., The Global Cognition, Frontal Lobe Dysfunction and Behavior Changes in Chinese Patients with Multiple System Atrophy. PLoS One, 2015. 10 (10): p. e0139773. Brown, R.G., et al., Cognitive impairment in patients with multiple system atrophy and progressive supranuclear palsy. Brain, 2010. 133 (Pt 8): p. 2382-93. Stankovic, I., et al., Cognitive impairment in multiple system atrophy: a position statement by the Neuropsychology Task Force of the MDS Multiple System Atrophy (MODIMSA) study group. Mov Disord, 2014. 29 (7): p. 857-67. Santangelo, G., et al., Comparative cognitive and neuropsychiatric profiles between Parkinson's disease, multiple system atrophy and progressive supranuclear palsy. J Neurol, 2018. 265 (11): p. 2602-2613. Ayodele, T., et al., Early-Onset Alzheimer's Disease: What Is Missing in Research? Curr Neurol Neurosci Rep, 2021. 21 (2): p. 4. Mendez, M.F., Early-Onset Alzheimer Disease. Neurol Clin, 2017. 35 (2): p. 263-281. Additional Declarations No competing interests reported. Supplementary Files supplementarymaterials.doc Cite Share Download PDF Status: Posted Version 1 posted 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-4702221","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":326306521,"identity":"24680226-6f92-45a9-b7e6-b8afd866f00c","order_by":0,"name":"Jing Zhao","email":"","orcid":"","institution":"The Second Hospital of Hebei Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jing","middleName":"","lastName":"Zhao","suffix":""},{"id":326306522,"identity":"5124c34d-35dd-4fcd-a35c-e2966f08d9bd","order_by":1,"name":"Yunsi Yin","email":"","orcid":"","institution":"Department of Neurology \u0026 Innovation Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, National Center for Neurological Disorders","correspondingAuthor":false,"prefix":"","firstName":"Yunsi","middleName":"","lastName":"Yin","suffix":""},{"id":326306523,"identity":"598a0469-a7d3-4c13-805e-d552854d3b68","order_by":2,"name":"Haoxun Yang","email":"","orcid":"","institution":"Department of Neurology \u0026 Innovation Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, National Center for Neurological Disorders","correspondingAuthor":false,"prefix":"","firstName":"Haoxun","middleName":"","lastName":"Yang","suffix":""},{"id":326306524,"identity":"d49e3912-321b-41ce-8db8-fd149cd49b9f","order_by":3,"name":"Qi Qin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvElEQVRIiWNgGAWjYDACZiBObGBg4GdmPviANC2S7WzJBsTbxAjUYnCex0yAKNV8x3kP3ni4w07O+DCDGQNDjU00QS2Sh/mSLRLPJBubHWZIe8BwLC23gZAWg8M8ZhKJbcyJ2w4zHDdgbDhMtJb6xM3NjG0SpGg5nLiBmZmNOC2Sh3mMgX45bixxmI3ZIIEYv/CdP2N48+eOajn+/vMfH3yosSGsheEAA4MEnJNAUDmGllEwCkbBKBgF2AAAriU9cPT9iVkAAAAASUVORK5CYII=","orcid":"","institution":"Department of Neurology \u0026 Innovation Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, National Center for Neurological Disorders","correspondingAuthor":true,"prefix":"","firstName":"Qi","middleName":"","lastName":"Qin","suffix":""}],"badges":[],"createdAt":"2024-07-08 02:57:41","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4702221/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4702221/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":62157376,"identity":"52b4f588-89f4-47d3-9067-b531e28a4e16","added_by":"auto","created_at":"2024-08-09 21:17:26","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":473292,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison neuropsychological scores among the three groups\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4702221/v1/b4969fe6ebe393f04ffef211.png"},{"id":62157378,"identity":"f29b6df0-36bb-499d-9d40-cddbf522cc28","added_by":"auto","created_at":"2024-08-09 21:17:26","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":471534,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of MRI scans among the three groups.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4702221/v1/e35d2f71799a3a9e2dce819e.png"},{"id":80023210,"identity":"b8cdf408-6294-4156-8484-b76766f1614e","added_by":"auto","created_at":"2025-04-07 05:33:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2116920,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4702221/v1/8d8b9ef6-080a-4b4e-b72d-28713f261504.pdf"},{"id":62157379,"identity":"8eb8a110-b6c0-4c4c-b0a7-e4e3b5209197","added_by":"auto","created_at":"2024-08-09 21:17:26","extension":"doc","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":17408,"visible":true,"origin":"","legend":"","description":"","filename":"supplementarymaterials.doc","url":"https://assets-eu.researchsquare.com/files/rs-4702221/v1/53f7bb611ce120c8abe5131b.doc"}],"financialInterests":"No competing interests reported.","formattedTitle":"Cognitive impairment in multiple system atrophy and spinocerebellar ataxias: A case series","fulltext":[{"header":"1. INTRODUCTION","content":"\u003cp\u003eSpinocerebellar ataxias (SCAs) are the most common subset of hereditary cerebellar ataxias[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. They are a group of progressive neurodegenerative diseases that are transmitted through autosomal dominance[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Via pathological changes characterized by cerebellar degeneration, the disease can affect not only the cerebellum and its connections but also the brainstem and spinal cord[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Despite the existence of over 40 genetic subtypes of SCAs, progressive ataxia is still the predominant clinical manifestation[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In recent years, with advances in genetic testing, research has achieved clear gene localization for most SCA subtypes [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Each subtype is named using the same convention: SCA followed by a number[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. For example, the SCA1, 2, 3, 6, and 7 types are caused by the gene amplification of CAG, which encodes polyglutamine. This results in the production of toxic polyglutamine proteins[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Some conventional mutations, including single nucleotide variants and small insertions or deletions, are also involved in the pathogenesis of hereditary ataxia[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAnother neurodegenerative disorder, multiple system atrophy (MSA), is a sporadic synucleinopathic disease [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], characterized by an adult-onset, relentless progression, and fatal neurodegeneration [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. MSA is clinically characterized by various combinations of parkinsonism with poor or no response to levodopa therapy, cerebellar ataxia, autonomic nervous system dysfunction and pyramidal symptoms[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Beyond its core clinical symptoms, MSA manifests with a number of nonmotor and motor features[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Based on the predominant motor symptomatology, MSA is divided into two types: cerebellar ataxia-predominant MSA (MSA-C) and parkinsonism-predominant MSA (MSA-P)[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The diagnosis of MSA mainly relies on medical history, a physical examination and magnetic resonance imaging (MRI)[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Clinical diagnosis of MSA is difficult due to the lack of definitive biomarkers and its wide clinical overlap with other neurodegenerative disorders, especially SCA subtypes.\u003c/p\u003e \u003cp\u003eMSA and SCAs share similar manifestations, including ataxia and pyramidal and extrapyramidal signs. Both SCA and MSA patients can exhibit atrophy and signal intensity changes in the cerebellum and brain stem on MRI scans. Accurate diagnosis can help to determine the best clinical management approach and improve prognosis. For this reason, genetic testing for SCAs, including SCA1, 2, 3, 6, 17 and DRPLA, may be crucial in the differential diagnosis of MSA patients without a family history. However, genetic testing involves second-generation sequencing, such as WES and NGS panels, which is not only expensive but also difficult to extend in primary hospitals.\u003c/p\u003e \u003cp\u003eDue to the aforementioned challenges of the current methods of diagnosis, researchers have paid more attention to the differences in the nonmotor clinical manifestations of MSA and SCA patients, especially cognitive function. Although dementia is an exclusion criterion for the diagnosis of MSA[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], recent research advances have revealed different degrees of cognitive impairment in most MSA patients[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Some studies have reported that prominent frontal involvement in MSA, as detected by functional and structural imaging, is related to cognitive dysfunction[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Other researchers have found that cognitive impairment in MSA patients is triggered by focal frontostriatal degeneration and is characterized by abnormalities in cortical and subcortical structures[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Similarly, cognitive impairment and even dementia have been described in many types of SCAs[\u003cspan additionalcitationids=\"CR31\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Functional imaging studies have shown cerebellar activation independent of motor control during executive or attentional tasks[\u003cspan additionalcitationids=\"CR34\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Some researchers have studied afferent and efferent connections of the cerebellum, particularly via corticopontocerebellar pathways, and their relationship with cortical association areas[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. The \u0026lsquo;cerebellar cognitive affective syndrome\u0026rsquo; was proposed[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Patients with cerebellar ataxia exhibit cognitive impairment when the sensorimotor CCAS is involved[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHere, we summarize 5 cases of MSA and 5 cases of SCAs confirmed by genetic testing among patients at the memory clinic of Xuanwu Hospital. We analyzed scores on various cognitive domains among the two patient groups and explored the damage to cognitive domains.\u003c/p\u003e"},{"header":"2. METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Subjects\u003c/h2\u003e \u003cp\u003eFive MSA patients and five SCA patients were enrolled consecutively from the memory clinic of Capital Medical University, Xuanwu Hospital, from March to September 2021. All five MSA cases were diagnosed according to the diagnostic criteria. All SCA cases were confirmed by genetic testing. Cognitive performance was assessed by a battery of objective neuropsychological tests. The study was approved by the Ethics Committee of Xuanwu Hospital. Written informed consent was obtained from each subject or from his or her guardian.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Clinical assessment\u003c/h2\u003e \u003cp\u003eDetailed clinical data, including main complaint, current medical history, past medical history and family medical history, were obtained from each patient and their families. Physical and neurological examinations were performed by more than two neurologists. A battery of laboratory blood tests and cerebrospinal fluid (CSF) examinations was conducted to exclude metabolic, toxic, and inflammatory causes. All five MSA patients were determined by diagnostic criteria, and all five SCAs patients underwent genetic testing to confirm SCA and its type. All patients underwent magnetic resonance imaging. Brain MRI scans were carried out according to the routine clinical method by a GE Discovery MR750 3.0T scanner. Conventional scanning sequences included T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), DWI, and fluid-attenuated inversion recovery (FLAIR). The extent of medial temporal atrophy (MTA) visible on MRI scans was assessed by visual rating scales as described previously.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Cognitive function assessment\u003c/h2\u003e \u003cp\u003eAll patients completed a battery of neuropsychological tests, including the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Clinical Dementia Rating Scale (CDR), Frontal Assessment Battery (FAB), Clock Drawing Test (CDT), Trail Making Test (TMT), Auditory Verbal Learning Test (AVLT), Boston Naming Test (BNT), Neuropsychiatric Inventory Questionnaire (NPI), Geriatric Depression Scale (GDS), and Activities of Daily Living Scale (ADL). Global cognition was evaluated in terms of MMSE, MoCA, and CDR scores. Attention and executive function were measured by the TMT-A, TMT-B, CDT and FAB; memory function was measured by the AVLT-Immediate Recall and AVLT-Delayed Recall scores; language was measured by the BNT and Animal Fluency score of the MoCA; and visuospatial abilities were measured by the Pentagon Copying score in the MMSE and the Cube Copying score in the MoCA. The associations between cognitive impairment (test scores) and imaging lesions were evaluated by Spearman correlation analyses.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Statistical Analysis\u003c/h2\u003e \u003cp\u003eAll statistical analyses were performed using the Statistical Package for Social Sciences (SPSS) for Windows, version V22.0 (IBM Corp., Armonk, NY). Descriptive statistics are presented in figures, means, standard deviations, and 95% confidence intervals. The analysis of patients involved the entire clinical sample. The MMSE, MoCA, ADL, CDR, CDR-SB, TMT-A, and TMT-B scores of MSA and SCA patients were compared using paired t tests. We then analyzed the differences in each cognitive domain among MSA, SCA and EOAD patients with Bonferroni and SNK-q tests.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. RESULTS","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Clinical manifestations\u003c/h2\u003e \u003cp\u003eIn the table, we provide a detailed summary of the medical history and neurological examinations of MSA and SCA patients. MSA patients experienced adult onset and had no family history of MSA. SCA patients also had adult onset; 3 patients had a family history of SCA, and 1 patient had SCA confirmed by genetic diagnosis. The sex ratio (males/females) of the MSA and SCA groups was 3:2. The educational attainment of both groups was 6 years or above. The duration of cognitive impairment was more than 1 year. All clinical characteristics of the two groups of patients are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic and clinical characteristics of patients in the 3 groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"18\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c15\" colnum=\"15\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c16\" colnum=\"16\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c17\" colnum=\"17\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c18\" colnum=\"18\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c7\" namest=\"c3\"\u003e \u003cp\u003eMSA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c12\" namest=\"c8\"\u003e \u003cp\u003eSCA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"6\" nameend=\"c18\" namest=\"c13\"\u003e \u003cp\u003eEOAD\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePatient number\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c14\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c15\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c16\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c17\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c18\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex (male\u0026thinsp;=\u0026thinsp;0, female\u0026thinsp;=\u0026thinsp;1)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOnset age (years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEducational attainment (years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCardiovascular history\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHypertension\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHyperlipidemia\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDiabetes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCognitive impairment duration (years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e\u003cb\u003eCognitive impairment\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMemory impairment\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eExecutive impairment\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eCalculation impairment\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eVisuospatial impairment\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAphasia\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOther neurological presentation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003edysosmia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003etremor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003edizziness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDepression or anxiety history\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eanxiety\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003edepression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003edepression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003edepression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003edepression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003eanxiety\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRelevant family history\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Cognitive impairment\u003c/h2\u003e \u003cp\u003eTo evaluate the overall cognitive function and cognitive status of patients, we used a series of neuropsychological scales. All patients were found to exhibit cognitive impairment and dementia. The mean MMSE scores of MSA and SCA patients were 21/30 and 21.7/30, respectively. The mean MoCA scores of MSA and SCA patients were 14.8/30 and 14.5/30, respectively. None of the patients exhibited normal cognitive function on the MoCA (scores\u0026thinsp;\u0026ge;\u0026thinsp;24). Outliers of TMT-A, TMT-B, and CDT scores confirmed the impairments in attention and executive function in patients with both disorders. Both groups had decreased ADL scores indicating significantly decreased activities of daily living. Except for two patients with SCA, the CDR scores reached a level of suspected dementia and above. In addition, we found 2 MSA patients (2/7, 40%) and 1 SCA patient (1.5, 20%) with abnormally high GDS scores. Except for 1 SCA patient, all patients exhibited abnormal NPI scores. This suggests that behavioral and psychological disorders are also common in these two diseases, which should be given more attention.\u003c/p\u003e \u003cp\u003eWe compared the scores on each cognitive domain between the MSA and SCA groups \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. The results showed that there was no significant difference in MMSE (p\u0026thinsp;=\u0026thinsp;0.59), MoCA (p\u0026thinsp;=\u0026thinsp;0.87), CDT (p\u0026thinsp;=\u0026thinsp;0.60), TMT-A (p\u0026thinsp;=\u0026thinsp;0.65), TMT-B (p\u0026thinsp;=\u0026thinsp;0.24), NPI (p\u0026thinsp;=\u0026thinsp;0.38) or GDS (p\u0026thinsp;=\u0026thinsp;0.2) scores. There was a difference in the overall CDR score (p\u0026thinsp;=\u0026thinsp;0.048) between the two diseases, which suggests that although cognitive impairment appears in both diseases, it differs in severity; more MSA patients suffered from cognitive impairment. In addition, we included 5 patients with EOAD diagnosed by genetic testing from Xuanwu Hospital. Comparison of neuropsychological scores among MSA, SCA and EOAD (a traditional cognitive impairment) patients revealed further differences. Significant differences arose between MSA and EOAD patients as well as SCA and EOAD patients, in ADL, CDR domain, and overall CDR scores. Thus, in terms of impairment in activities of daily living and cognition, EOAD patients suffered to a greater extent than MSA and SCA patients.All cognitive domains scores of the three groups of patients are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eNeuropsychological assessments of patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"18\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c15\" colnum=\"15\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c16\" colnum=\"16\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c17\" colnum=\"17\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c18\" colnum=\"18\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e \u003cp\u003eMSA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"6\" nameend=\"c12\" namest=\"c7\"\u003e \u003cp\u003eSCA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"6\" nameend=\"c18\" namest=\"c13\"\u003e \u003cp\u003eEOAD\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient number\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c14\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c15\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c16\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c17\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c18\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMMSE score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMoCA score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCDT (0\u0026ndash;15)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCDT (0\u0026ndash;3)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eADL score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCDR domain score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e4.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e4.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCDR total score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHIS score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTMT-A (s)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e109\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e121\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e89.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e150.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e141\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e72.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e140.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e113\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e47.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e147\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e \u003cp\u003e150\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTMT-B (s)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e130\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e300\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e118.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e300\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e300\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e126.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e167.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e126\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e86.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e170\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e156\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e300\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNPI patient score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNPI family score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGDS score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c18\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Imaging results\u003c/h2\u003e \u003cp\u003eVarying extents of brainstem and cerebellar atrophy were found in both MSA and SCA patients by cranial magnetic resonance imaging \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. The coronal MRI of both patients did not show obvious atrophy of the hippocampus, and the imaging findings were consistent with clinical manifestations, which were in line with the characteristics of the diseases. There was no significant difference in the cranial magnetic resonance imaging findings between the two groups. These findings did not explain whether the degrees of cerebellar or brainstem atrophy were related to cognitive function (e.g., MMSE and MoCA scores). In the future, we hope to recruit more MSA and SCA patients and collect additional imaging data. Objective imaging indicators were included in a detailed quantitative analysis of brainstem volume, total cerebellum volume, total cerebellar gray matter volume, and white matter volume. We aim to collect more sensitive morphometric or functional magnetic resonance imaging data to observe the correlation between cerebellar and brainstem volume and cognitive impairment in these two disorders, to determine if there is a significant difference between them.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4. DISCUSSION","content":"\u003cp\u003eCurrently, the two most prevalent neurodegenerative diseases that can result in ataxia are MSA and SCAs. They are mostly diagnosed based on clinical symptoms, characteristic imaging findings, laboratory examinations, relevant family history and genetic testing. The current diagnosis of these diseases focuses more on movement disorders and abnormal autonomic function, while few summaries or related reports on the characteristics of cognitive function have been published. To our knowledge, no studies have compared the domain-specific characteristics of cognitive impairment between these diseases; thus, our work is groundbreaking as well as innovative. We recruited five patients with SCA confirmed by genome-wide analysis and 5 patients clinically diagnosed with MSA. We conducted a series of neuropsychological assessments to evaluate patients' overall cognitive function, numeracy, executive function, language, visuospatial abilities, and disease severity. Statistical analysis was used to investigate whether MSA and SCA patients differed in each cognitive domain. The results showed that the two groups significantly differed in CDR scores but not in MMSE/MoCA, CDT, TMT, AVLT, BNT, or Cube Copying scores. This result indicated that both MSA and SCA patients exhibited impairments in overall cognitive function, executive function and activities of daily living. Statistical analysis showed significant group differences in CDR scores but not in MMSE/MoCA, CDT, TMT, AVLT, BNT, or Cube Copying scores. Thus, we believe that both MSA and SCA are clinically characterized by damage to multiple systems that may cause cognitive impairment. The two groups had no significant differences in overall cognitive function, computing power, executive function, language, or visuospatial abilities, although they significantly differed in the severity of cognitive impairment. Specifically, MSA patients exhibited greater cognitive impairment than SCA patients. Thus, our study demonstrates that it is difficult to distinguish these two diseases based on cognitive function characteristics.\u003c/p\u003e \u003cp\u003eAlthough both MSA and SCA are clinically characterized by damage to multiple systems and may cause cognitive impairment, MSA patients exhibited more severe cognitive impairment than SCA patients. The results of this study align with the characteristics of cognitive impairment reported in previous studies. In the MSA consensuses of 1999 and 2000, cognitive impairment was considered a warning sign of MSA diagnosis[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan additionalcitationids=\"CR22 CR23\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. With recent research advances, increasing evidence has shown that MSA patients exhibit different degrees of cognitive impairment[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] and that approximately 20\u0026ndash;30% of MSA patients suffer cognitive impairment[\u003cspan additionalcitationids=\"CR38\" citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. This suggests that cognitive impairment can be used as a differential diagnosis for MSA and other neurodegenerative diseases. Some studies have suggested that localized frontostriatal degeneration induces cognitive impairment in MSA patients, characterized by abnormalities in cortical and subcortical structures[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. This impairment is mainly manifested in executive function, memory, language and visuospatial abilities[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Moreover, a study by the Neuroscience Working Group of the MDS-MSA research group found that cognitive impairment in MSA patients was most prominent in executive function and verbal fluency, followed by attention, memory, and visuospatial abilities[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. The degree of cognitive impairment in MSA patients was similar to that in patients with Parkinson's disease and less severe than that in patients with progressive supranuclear palsy[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. The incidence of cognitive impairment gradually increases with the duration of the disease and worsens with its progression[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. These studies all support our conclusions that both diseases may cause cognitive impairment and that MSA patients exhibit more severe cognitive impairment. In addition, we compared MSA and SCA patients and expanded the cognitive impairment characteristics for their diagnosis.\u003c/p\u003e \u003cp\u003eSCAs, a type of neurodegenerative disease with ataxia as the main manifestation, can also cause cognitive dysfunction[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan additionalcitationids=\"CR31\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. The conventional view is that the cerebellum is involved in motor control and assists in the completion of movement. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. As early as 1970, clinical and experimental data suggested the involvement of the cerebellum in the regulation of nonmotor functions[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Many researchers have examined the contribution to cognitive function of the cerebellum[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Among them, Schmahmann and Sherman reported that patients with congenital or acquired cerebellar disease are more prone to a range of cognitive impairments, exhibiting widespread executive dysfunction, including deficits in planning, set-shifting, abstract reasoning, spatial cognition (including visuospatial memory) and verbal fluency. Individuals also undergo personality changes characterized by inappropriate and childlike behaviors and flattened affect. Linguistic difficulties include dysfunction in naming, grammar and prosody. Schmahmann and Sherman termed this constellation of cognitive impairments cerebellar cognitive affective syndrome (CCAS) and suggested that it may be the result of disruptions to the cerebrocerebellar circuitry[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. The mechanism underlying cognitive impairment in patients with SCAs has not been fully elucidated[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. The frequencies of different subtypes of cognitive impairment also differ[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Previous studies have suggested that cognitive deficits in SCA1 and SCA3 are mainly manifested in attention, visuospatial perception, executive function, language fluency, immediate memory and long-term memory[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Approximately 5\u0026ndash;25% of patients with advanced SCA1 exhibit cognitive impairment[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Burke et al. found that SCA1 patients have significant executive function deficits, and other studies have reported that this dysfunction is more prominent than that in the control group and other SCA subtypes[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. A persistent feature of SCA3 is the presence of deficits in executive function and visuospatial abilities[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Both SCA1 and SCA3 patients may exhibit language and memory impairment[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. In conclusion, each subtype of SCA has its own characteristic cognitive impairment. In-depth study of the characteristics of each subtype of cognitive impairment can help to improve disease management and patient quality of life[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Moreover, these same characteristics can be used as predictors of disease. However, the mechanism underlying cognitive impairment in SCA patients has not been fully elucidated. The frequency of different cognitive impairments also varies. Cognitive impairment was observed in SCA1, 2, 3, 6, 7, 8, 10, 12, 17, 19, 21, and DRPLA, while dementia was reported in SCA2, 3, 8, 12, 19, and DRPLA. Cognitive impairment can also occur in patients with SCA13[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMoreover, we revealed that genotyping was still the key method of distinguishing MSA and SCA. Five SCA patients included in our study were diagnosed with SCA1 and SCA3 by genetic diagnosis. The neuropsychological scores showed varying degrees of cognitive impairment. SCAs are a group of highly heterogeneous inherited neurodegenerative diseases with complex genetic and phenotypic features[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Among them, SCA1, 2, 3, 6, 7, etc., are caused by amplification and unstable polymorphism in the coding region of the gene and the mutation of the trinucleotide CAG repeat sequence. The product of this gene is a protein called ataxin. This mutated protein has toxic effects that can lead to degeneration of neural function[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe cognitive function of EOAD patients and SCA patients were compared, and we found that there were differences in ADL, CDR domain and CDR total scores between SCA and EOAD patients. These differences in cognitive impairment may be due to the different pathophysiological mechanisms. These findings may inform differential diagnosis at the cognitive level in clinical work. The most common neurodegenerative disease, AD, often occurs in elderly individuals. However, approximately 4\u0026ndash;5% of patients develop early-onset Alzheimer's disease (EOAD) before the age of 65 years[\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. Most EOAD cases are sporadic, but approximately 5% are due to autosomal dominant inheritance. Amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) are the most common mutations in EOAD and can lead to the overproduction and deposition of amyloid beta, neuronal degeneration and eventually dementia[\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. Another important theory is that the hyperphosphorylated tau protein affects the stability of the neuronal cytoskeleton tubulin, resulting in neurofibrillary tangles that damage the function of neurons and eventually lead to cognitive impairment[\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. The pathophysiological mechanism underlying SCA-induced cognitive impairment has not been fully elucidated. Some studies have suggested that it is caused by the disruption of cerebellar circuits at different levels of the central nervous system. In 1991, Schmahmann proposed that the cerebellum is involved in higher cortical functions after studying the afferent and efferent connections of the cerebellum, particularly the corticopontocerebellar pathway[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. In 1997, Schmahmann and Sherman proposed the cerebellar cognitive affective syndrome. These functional deficits are thought to result from a disruption of pathways connecting the cerebellum to the prefrontal, posterior parietal, superior temporal, and limbic areas. Neuroimaging, neuropsychological, and neuroanatomical data suggest that the cerebellum contributes to executive control. Neuroimaging studies have demonstrated cortical damage, white matter involvement, cerebral hypoperfusion, and hypometabolism in SCA patients. However, how these impairments relate to cognitive function is unclear. By assessing the correlations of cognitive function with brain atrophy, cerebral perfusion, and metabolism, mechanisms underlying cognitive impairment may be revealed.\u003c/p\u003e \u003cp\u003eOur study has a few limitations. First, the sample size was relatively small. Nevertheless, a series of well-established neuropsychological assessments detected difference between the two diseases, suggesting that we should devote more attention to the cognitive characteristics of these two diseases. Second, we included only cross-sectional data in this study. In the future, we will carry out a larger-scale cohort study to further analyze the characteristics of impairment in each cognitive domain of MSA and SCA patients. Clinical management of patients in later stages and rehabilitation training benefit from the identification and analysis of these diseases at the cognitive level, which can delay their progression.\u003c/p\u003e"},{"header":"5. CONCLUSION","content":"\u003cp\u003eBy summarizing and comparing the clinical history and neuropsychological scores of patients with MSA and SCA, we hoped to better distinguish these two common neurodegenerative diseases that clinically manifest mainly as movement disorders. We first assessed the characteristics of cognitive impairment in these two diseases. We found that, consistent with previous research, both disorders showed varying degrees of cognitive impairment, including impairment of overall cognitive function, attention, and executive function. Both MSA and SCA decreased the ability to perform activities of daily living. Statistical analysis revealed a difference in the severity of cognitive impairment, with MSA patients experiencing more severe impairment. Finally, we found it difficult to distinguish between these two diseases in terms of cognitive function; thus, further in-depth and large-scale studies are needed. Genetic diagnosis remains critical for differentiating the two diseases. This study provides preliminary findings regarding the use of cognitive impairment to distinguish the two diseases as well as clues for differential diagnosis.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee as well as those of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZhao.J. analysed data, drafted and revised the manuscript. Yin.Y.S. performed data collection, followed patients and revised manuscript. Yang.H.X. performed stastical analysis, data interpretation. Qin.Q. designed the study, analysed data, drafted and revised the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe work was supported by Young Elite Scientists Sponsorship Program by CAST (2021QNRC001), Beijing Hospitals Authority Innovation Studio of Young Staff Funding Support (202118), Beijing Nova Program (Z211100002121051), National Natural Science Foundation of China (82201568).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailablility of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analysed during the current study are not publicly available due to privacy or ethical restrictions. But are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study has been approved by the Ethics Committee of Xuan Wu Hospital,Capital Medical University,Beijing,China. 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Therefore, it is challenging to differentiate MSA and SCAs according to clinical symptoms, especially in the early stage. Currently, the diagnosis still relies on auxiliary inspection and genetic testing. The difference in cognitive symptoms between MSA and SCAs has not been fully investigated. Hence, the aim of this study was to analyze the differences in cognitive impairment between MSA and SCAs.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eFive MSA patients and 5 patients with SCAs were recruited from the memory clinic of Xuanwu Hospital from March to September 2021. We collected detailed clinical information, imaging data, neuropsychological scales and genetic analysis of the patients. Then, we compared the differences in each cognitive domain between MSA and SCA patients.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eComparison of SCA and MSA patients revealed that MSA patients had lower scores on the Clinical Dementia Rating Scale (CDR). There were no statistically significant group difference in global cognitive functioning, as indicated by Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eBoth MSA and SCAs present with cognitive impairment, but MSA presents more obvious symptom severity.\u003c/p\u003e","manuscriptTitle":"Cognitive impairment in multiple system atrophy and spinocerebellar ataxias: A case series","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-09 21:17:21","doi":"10.21203/rs.3.rs-4702221/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"41e3182a-6e0c-40da-b1ce-40b600d2f822","owner":[],"postedDate":"August 9th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-04-07T05:25:18+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-09 21:17:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4702221","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4702221","identity":"rs-4702221","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}