Find-DLB - A naturalistic cohort of patients presenting with clinical features of Dementia with Lewy bodies to a specialized cognitive clinic

Find-DLB - A naturalistic cohort of patients presenting with clinical features of Dementia with Lewy bodies to a specialized cognitive clinic | 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 Find-DLB - A naturalistic cohort of patients presenting with clinical features of Dementia with Lewy bodies to a specialized cognitive clinic Stephanie Gravett, Sara Garcia-Ptacek, Anna Rennie, Nenad Bogdanovic, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7865542/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 Purpose Dementia with Lewy Bodies (DLB) is a common neurodegenerative disorder, yet difficult to diagnose. Carefully selected research cohorts may not represent the clinical reality. We aimed to characterize a naturalistic cohort of patients with clinical features of DLB, reporting their final diagnosis, clinical features, and cognitive profile. Methods Patients were recruited from a specialized cognitive clinic. Data from patient visits were collected from health records, such as biomarkers, cognitive screening, core clinical features and neuropsychological assessment. We used normative data to assess distribution of impairment in patients with DLB and Parkinsons disease (PD) with and without dementia. Results A total of 143 patients were included in the cohort. Following specialized dementia evaluation, 88 patients fulfilled clinical criteria for DLB, 35 patients for PD with dementia (PDD), 14 had mild cognitive impairment (MCI), and the remaining six patients had other types of dementia. Parkinsonism was the most common core clinical feature (87%), followed by visual hallucinations (65%), cognitive fluctuations (52%) and, lastly, probable REM-sleep behavior disorder (RBD, 47%). A majority of DLB patients had cognitive impairment on visuospatial constructive, attentional and executive tasks, and visual memory. Conclusions The differential diagnosis of DLB may be difficult within a clinical context because other cognitive disorders frequently present with core features of DLB. The cognitive profile and frequency of core clinical features in the DLB group was generally in line with previous reports. Probable RBD was lower than in other cohorts, which may reflect challenges in collecting this information in a clinical interview. Geriatrics & Gerontology Neurology DLB PDD Synucleinopathy Lewy body dementia Neuropsychology Biomarkers Figures Figure 1 Figure 2 Key summary points Aim: We aimed to characterize a naturalistic cohort of patients with symptoms of Dementia with Lewy Bodies (DLB). Findings: While the majority (88/143) received a clinical diagnosis of DLB, 33 patients received a diagnosis of Parkinson’s disease dementia, and 22 patients received a diagnosis of Mild cognitive impairment or other dementia. Parkinsonism was the most frequent core feature, and DLB patients commonly showed impairment in visuospatial, attentional, executive, and visual memory tasks. Message: The differential diagnosis of DLB is challenging in a clinical setting due to overlapping features and requires careful review of clinical features and biomarkers. 1. Background Dementia with Lewy bodies (DLB) is a common neurodegenerative cause of dementia, characterized by core clinical features of parkinsonism, visual hallucinations, cognitive fluctuations, and REM-sleep behavior disorder (RBD) ( 1 ). A previous systematic review reported DLB to account for about 5% of dementia cases, although prevalence values ranged from 0.3 to 24.4% ( 2 ). This wide range highlights differences between cohorts and disparities in how DLB is diagnosed and participants recruited to studies across the globe. Indeed, DLB is known to be under-diagnosed, and differences in prevalence rates in specialized clinics may be influenced by factors such as sensitivity to core clinical features, education or training of clinical staff, and research focus of specific centers ( 3 , 4 ). One reason for the diagnostic challenges is the significant overlap between DLB and other disorders such as Alzheimer’s disease (AD), Parkinson’s disease with dementia (PDD), and cerebrovascular disease. While clinical presentations may converge, there is also pathological overlap. Around 50% of DLB patients have concomitant AD pathology ( 5 – 7 ). This concomitant AD pathology and positivity of AD biomarkers confound the diagnostic accuracy in DLB ( 8 ). Additionally, there are challenges differentiating DLB from PDD, especially when cognitive impairment progresses rapidly and occurs early during Parkinsons disease (PD). Cognitive profiling with neuropsychological assessment is an important diagnostic tool within dementia evaluation to differentiate level and type of cognitive impairment. The cognitive profile in DLB generally constitutes impairment in visual processing, attention and executive functions with relative sparing of memory and naming, differentiating it from AD ( 1 ). The differences in the cognitive profile of DLB versus PDD have been partially explored but results are not conclusive ( 9 , 10 ). While several DLB cohorts have been well characterized, these cohorts were primarily research-oriented ( 11 – 13 ), so that study participants may be different than those presenting at specialized cognitive clinics. There are fewer publications of naturalistic clinical cohorts describing DLB patients ( 14 ), and the clinical journey of patients presenting to the cognitive clinic with a suspicion of DLB is generally not reported and largely unknown. Investigating this patient group is thus relevant to capturing a more complete picture of DLB and understand potential bias in the reported profiles of patients eventually being recruited to well-characterized research-oriented cohorts. The current study describes Find-DLB, a naturalistic clinical cohort of patients presenting with clinical features of DLB to a specialized cognitive clinic. The goal was to present a realistic view of the diagnostic flow, which may help increase the knowledge on the day-to-day challenges clinicians face when differentiating DLB from other neurodegenerative diseases, non-degenerative causes of cognitive impairment such as psychiatric illnesses, and normal ageing. We aimed to present baseline demographic, biomarker, and neuropsychological data of the original cohort as well as stratified by diagnostic group after classification in naturalistic clinical rounds. 2. Methods Study setting The Cognitive clinic at Karolinska University Hospital Huddinge is a specialist unit for cognitive disorders. Patients are referred from their primary care facility or occasionally from other specialist units on suspicion of cognitive disorder. Approximately 600 referrals are accepted each year. Both suspected early onset ( 65y) patients are evaluated at the clinic. Patients > 65y are usually from the close geographical area, while < 65y patients may be referred from the entire Stockholm Region, which comprises several municipalities over an area of approximately 6500 square km, with a population of 2 450 000 in 2023 ( 15 ). Second opinions may be referred from other Swedish regions across the country as well. Prior to referral, most patients have undergone a basic dementia evaluation in primary care, often including a computer tomography (CT) scan or magnetic resonance imaging (MRI) of the brain, blood sampling, assessment of activities of daily living (ADL), as well as cognitive screening with the Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), or the Rowland Universal Dementia Assessment Scale (RUDAS) ( 16 – 18 ). As reported in Fig. 1 , the specialist dementia evaluation can include a range of clinical assessments, neuroimaging modalities, and lumbar puncture depending on clinical suspicion. Diagnoses are determined at multi professional rounds comprised of 4–10 people, including physician, neuropsychologist, nurse, occupational therapist, and speech and language pathologist. All relevant information from the examinations is presented and diagnosis is determined by consensus principle. The ICD-10 is used for diagnostic coding. Patients are often subject to follow up at the clinic, and they may therefore repeat some evaluations. Assessments might be added by the responsible physician during follow-up to help differentiate the diagnosis in complex cases. The full process is illustrated in Fig. 1 . Participants Find-DLB was started in 2020 with the main goal of improving detection of DLB in specialized cognitive clinics in Stockholm, Sweden. Find-DLB includes a retrospective and a prospective approach, including retrospective patients up to 2020, and recruiting patients prospectively from 2020. Patients were considered for inclusion if there was suspicion of any core clinical features of DLB, namely visual hallucinations, parkinsonism, cognitive fluctuations or probable RBD. Some patients were included upon their first doctor’s visit, while other patients were retrospectively recruited at follow up after receiving their diagnosis. Patients are excluded from Find-DLB if they terminated their evaluation before receiving a diagnosis at diagnostic rounds. Diagnostic procedure Find-DLB being a naturalistic project, the procedure during diagnostic rounds follows the general Swedish guidelines of current clinical criteria. For research purposes, clinical diagnoses were retrospectively cross checked with the 2017 consensus criteria for DLB ( 1 ) by a senior physician (V.J.) and a neuropsychologist (S.G.) together. Mild cognitive impairment (MCI) was diagnosed in accordance with consensus criteria, if there is objective cognitive impairment on neuropsychological tests with relatively spared level of function in ADL ( 19 ). Additional criteria were applied to establish the diagnosis of MCI due to PD (PD-MCI) ( 20 ) or MCI with Lewy bodies (MCI-LB) ( 21 ). For patients who presented to the clinic with parkinsonism, the 1-year rule of onset between parkinsonism and dementia was applied to differentiate between DLB and PD ( 1 ). Unclear cases were retrospectively reviewed by a senior physician (V.J.), who decided the final diagnosis based on all available information. Patients with two clinical diagnoses, i.e. both a diagnosis of AD and DLB, were included in the DLB group for the purpose of the current study. Assessments Clinical features Clinical data regarding DLB core clinical features was collected through the electronic health records. Self-, caregiver-, and clinician-reported symptoms were all considered. Parkinsonism was coded as present if the records included descriptions of cardinal parkinsonian features of either bradykinesia, resting tremors, or rigidity. Visual hallucinations were considered present if there was mention of fully formed visual hallucinations. Fluctuations were coded as present if reported as either clear fluctuating cognitive impairment or alertness as well as passing episodes of confusion or delirium. Probable RBD was considered present if there were reported symptoms such as arm flailing, thrashing, punching, screaming or shouting, recurring nightmares, and falling out of bed during sleep time. If a symptom was negated it was coded as not present. If there was no clear mention of a core symptom, it was considered missing data. Several patients reported unspecific symptoms such as visual illusions, presence phenomena, and nightmares without other symptoms of RBD, which were not included in our current analysis. Neuropsychological assessment A subgroup of patients (n = 96, 67% of the total cohort, n = 143) underwent extended neuropsychological evaluations performed by a psychologist. The remaining 47 patients (33%) did not undergo neuropsychological assessment due to low performance on cognitive screening test, severe impairment in ADL, or frailty. Raw data from neuropsychological tests were available for 68 patients (48% of the total cohort) due to failure to submit raw scores in the electronic health records. Most patients underwent neuropsychological assessment within 6 months of their final diagnosis. However, six patients (6%) performed neuropsychological assessment more than two years before their dementia diagnosis. These assessments were carefully reviewed. Based on the available information, five of these patients were included in a group of patients without dementia, referred to below as the Non-Dementia (ND) group. The remaining patient was excluded from further analyses due to insufficient information. All neuropsychological tests were administered at a single visit, extending for approximately 2–3 hours. Since Find-DLB is a fully naturalistic cohort, there was variation in neuropsychological tests used across patients over time. Only tests with scores available for > 50% of the subgroup with neuropsychological assessment were included in this article, including the following: Verbal Wechsler Adult Intelligence Scale 4th edition (WAIS-IV) ( 22 ) and Wechsler Adult Intelligence Scale 3rd edition (WAIS-III) ( 23 ) Subtests: Information, Similarities. Memory : Rey Auditory Verbal Learning Test (RAVLT) without distraction list ( 24 ): Total score over 5 learning trials and free delayed recall (30 minutes after learning trials); Rey Complex Figure Test (RCFT), immediate recall. Visuospatial : WAIS-IV and WAIS-III Subtests: Block Design, RCFT ( 25 ): Copy trial Executive/attention/processing speed : WAIS-IV and WAIS-III Subtests: Digit Span, Coding, Arithmetic, Matrix reasoning; Trail Making Test A & Trail Making Test B ( 26 ): Time to complete; Delis–Kaplan Executive Function System (D-KEFS) Trail Making Test 2 & 4 ( 27 ): Standardized score for time to complete. Neuropsychological raw data was standardized to z-scores using normative data from regression-based norms used in the Cognitive clinic, stratified for age, education, and sex ( 28 ). For WAIS and D-KEFS subtests, age-appropriate scaled scores were used. A total of 57 patients performed subtests from WAIS-IV and 7 patients completed subtests from WAIS-III instead. To facilitate overview of the cognitive functions and domains, corresponding tests from different versions were combined. Specifically, WAIS-III and WAIS-IV standardized scores were combined into single variables for each subtest. Time to complete Trail Making Test A and D-KEFS Trail Making Test 2, as well as Trail Making Test B and D-KEFS Trail Making Test 4, were standardized and combined into two variables: TMT Number sequencing and TMT Letter number switching. For WAIS subtests, strong correlations between WAIS-III and WAIS-IV versions of the subtests have been previously reported, motivating their combination ( 22 ). For the Trail Making Test, the placement, number of stimuli and size of the paper differ while the tasks are identical and can, therefore, be combined. After standardization and combination of tests as described above, scores were considered impaired if z-score was ≤ -1.5 SD, in accordance with established clinical criteria ( 29 ). Discontinuation of a test due to the patient being unable to complete it was considered an impaired test: WAIS-IV Block design was discontinued for one patient, Trail Making Test B for nine patients, D-KEFS Trail Making Test 4 for two patients, and RCFT copy for three patients. Biomarkers Cerebrospinal fluid (CSF) biomarker status for amyloid-beta 1–42 and phosphorylated tau 181 (p-tau) was coded as positive or negative if below or above the center-specific cut-off. Since data was collected over a large time span, methods and cut-offs have changed. Due to clinical usefulness and interpretability, data is only presented as positive or negative. The applied cut-offs are described elsewhere( 30 – 32 ). DaT-scan was coded as positive or negative based on the report from the nuclear medicine department. DaT-scan in one patient was deemed inconclusive, and it was excluded from analysis of group differences. The current article focusses on introducing the Find-DLB cohort and describing the naturalistic diagnostic procedure. Further data beyond the availability of MRI, EEG, and FDG-PET will be presented in future modality-specific publications. Statistics Descriptive data is presented as count and percentage or mean and standard deviation. T-test or ANOVA-test with paired post hoc analyses with the Tukey adjustment were performed on continuous variables. Chi²- tests were used for categorical variables, and Fisher-Freeman-Halton test was applied when any cell count was < 5, with paired post hoc Fisher exact tests. Significance level was pre-determined at p ≤ 0.05 in all analyses. Years of education were missing for four patients who underwent neuropsychological evaluation. The regression-based norms require years of education to calculate individual predicted values. Out of these four patients, two had information on occupation, and an estimated level of education was derived from the lowest level needed for the registered occupation within the Swedish educational system. For the other two patients, there was insufficient information so that predicted values of education were estimated based on a linear regression model including the raw score of Information from WAIS-IV as a common proxy of educational attainment ( 33 , 34 ) along with age, gender, and diagnosis (i.e. DLB, PDD or MCI). MMSE was missing for 39 patients who instead had performed the MoCA-test. An estimated MMSE-score was calculated from MoCA-scores based on a conversion table published elsewhere ( 35 ). 3. Results Whole Find-DLB cohort 144 patients were eligible for inclusion in the Find-DLB cohort. One patient was excluded due to termination of the evaluation prior to a diagnosis. Out of the remaining 143 patients, 88 patients fulfilled criteria for DLB (83 probable DLB and 5 possible DLB), with 8 of them receiving a clinical diagnosis of both DLB and AD. Out of the remaining patients, 35 were diagnosed with PDD; 2 patients fulfilled clinical criteria for AD with atypical presentation such as prominent visuospatial impairment and neuropsychiatric symptoms; and 4 patients were included in the “Other dementias” group, which included Corticobasal Degeneration and Dementia not otherwise specified. Furthermore, 14 patients received a clinical diagnosis of MCI (8 PD-MCI, 2 MCI-LB, and 4 had an MCI diagnosis without any specified cause) and were included in the Non-Dementia (ND) group. The two AD patients and the “Other dementias” group were excluded from further analysis due to small group sizes. Table 1 Demographics and clinical features, Whole cohort (N = 143) Variable Mean (SD), or count N Age 70.8 ( 7 , 5 ) 142 Sex (male) 102 (71%) 143 Years of education 12.3 ( 3 , 4 ) 119 MMSE 24.1 ( 3 , 7 ) 142 Parkinsonism 120 (87%) 138 Visual hallucinations 87 (65%) 134 Probable RBD 55 (47%) 118 Cognitive fluctuations 50 (52%) 97 MMSE = Mini Mental State Examination. RBD = REM-sleep Behavior Disorder Demographic characteristics and biomarkers of the whole Find-DLB cohort (N = 143) Table 1 shows demographic characteristics and presence of core clinical features within the whole cohort. The mean age at final diagnosis was 70.8 years, ranging from 52–88 years. Approximately 71% were male and the mean years of education was 12.3. The mean MMSE score was 24.1, ranging from 11–30. Parkinsonism was the most frequent core clinical feature, with 87% of the patients experiencing at least one cardinal feature of parkinsonism. 65% experienced visual hallucinations, 52% had cognitive fluctuations, and 47% had symptoms of probable RBD. In this cohort, cognitive fluctuations was the core symptom least frequently screened for and reported in health records, with data available only for 68% of the cohort. 73% of the whole cohort completed a brain MRI and 74% an EEG exam, while a smaller proportion had an FDG-PET scan (33%). 50% of the patients completed a DaT-scan and 93% of those had a result consistent on reduced dopamine transporter uptake in basal ganglia (coded as positive biomarker result in Table 2 ). One patient had an inconclusive DaT-scan result according to the clinical report. Amyloid positivity in CSF was more common (20%) than p-tau positivity (8%). Table 2 Available modalities and biomarkers in the whole Find-DLB cohort (n = 143) Variable Count Positive Negative MRI 105 (73%) EEG 106 (74%) Neuropsychology 96 (67%) FDG-PET 54 (38%) DaT-Scan 72* (50%) 67 (93%) 4 (6%) CSF Amyloidβ42 112 (78%) 22 (20%) 90 (80%) CSF P-tau 111 (78%) 9 (8%) 102 (92%) *n = 1 inconclusive. MRI = Brain Magnetic Resonance Imaging. EEG = Electroencephalography. FDG-PET = Fluorodeoxyglucose Positron Emission Tomography. DaT-Scan = Dopamine Transporter Scan. CSF Amyloidβ42 = Cerebrospinal Fluid Amyloid beta 42. CSF P-tau = Cerebrospinal Fluid Phospholyrated Tau. Demographic characteristics and biomarkers by diagnostic group (DLB, PDD and ND) Table 3 shows the main demographic characteristics and biomarker data for DLB, PDD and ND (the last is for the Non-Dementia group, which is composed of MCI patients). The DLB group was statistically significantly older compared to the ND group. There were no significant group differences in sex distribution or years of education. As expected, ND performed significantly better on MMSE compared to both DLB and PDD. Parkinsonism was the most frequent core clinical feature for all diagnostic groups with 100% of PD patients, almost 90% of DLB patients and 67% of ND patients experiencing parkinsonism. Statistical testing shows that Parkinsonism was significantly more common in PDD compared to ND. Both DLB (69%) and PDD (67%) had a statistically significantly higher frequency of visual hallucinations compared to ND (20%), but there were no significant group differences regarding probable RBD or cognitive fluctuations. In the smaller subsample with available CSF biomarkers and DaT-scan, 27% of DLB participants were amyloid-positive in CSF, which was significantly more frequent than in PDD where only 4% were amyloid-positive. There were no group differences regarding positivity on DaT-scan or P-tau in CSF. DaT-scan was only performed for 51% of all participants within these diagnostic groups. For the remaining participants, DaT-scan status is unknown. Table 3 Group comparison of demographics and biomarker status of available data Variable DLB = 88 N PDD = 35 N ND = 14 N p-value Age, years 72.5 (7.0) 87 69.4 (7.6) 35 66.6 (6.9) 14 0.005 a Sex, male 62 (71%) 88 24 (69%) 35 11 (79%) 14 0.846 Education, years 12.0 (3.2) 77 12.4 (3.5) 25 14.0 (4.4) 10 0.226 MMSE, total score 23.6 (3.9) 87 24.0 (3.5) 35 26.9 (2.6) 14 0.010 a,b Parkinsonism, presence 77 (90%) 86 34 (100%) 34 8 (67%) 12 0.005 b Hallucinations, presence 59 (69%) 85 22 (67%) 33 2 (20%) 10 0.010 a,b Probable RBD, presence 37 (46%) 80 16 (57%) 28 1 (14%) 7 0.134 Fluctuations, presence 41 (57%) 72 6 (38%) 16 2 (40%) 5 0.291 CSF Amyloid β42, positive 18 (27%) 68 1 (4%) 27 2 (18%) 11 0.025 c CSF P-tau, positive 5 (7%) 68 2 (8%) 26 1 (9%) 11 1.000 DaT-scan, positive 46 (96%) 48 16 (94%) 17 4 (80%) 5 0.215 Mean (standard deviation) and count (percentage) are reported as detailed in the table. a) DLB vs ND. b) PDD vs ND. c) DLB vs PDD. DLB = Dementia with Lewy Bodies. PDD = Parkinson’s Disease Dementia. ND = Non-Dementia group (composed of MCI patients). MMSE = Mini Mental State Examination. RBD = REM-Sleep Behavior Disorder. Pos DaT-Scan = Positive Dopamine Transporter Scan. CSF Amyloid beta 42 = Cerebrospinal Fluid Amyloid beta 42. CSF P-tau = Cerebrospinal Fluid Phospholyrated Tau. Neuropsychological profile The subsample with neuropsychological data included 68 patients. Six patients had completed the neuropsychological assessment > 2 years before final diagnosis: one patient with DLB and five patients with PDD. The DLB patient had an MCI-LB diagnosis at previous visits. The five PDD patients had completed the assessment before converting to dementia. Therefore, they were grouped with the PD-MCI patients in the Non-Dementia (ND) group. To keep that group specific for PD, the remaining MCI patients were excluded from further analysis (two with MCI-LB and two MCI without specified cause). The final groups for comparing neuropsychological test performance were as follows (n = 63): DLB (n = 43), PDD (n = 9), and ND (n = 11). Table 4 shows key demographic variables and neuropsychological test performance of DLB, PDD, and ND groups. DLB were older than PDD and ND, significantly so compared to PDD (p = 0.037). There were no significant differences in years of education (p > 0.05). Neuropsychological test performance was classified into normal or impaired and percentage of impairment was reported (Table 4 ) and plotted to build impairment profiles (Fig. 2 ). Due to the small sample size in the neuropsychological subsample, we first inspected percentage of impairment qualitatively. We observed that DLB generally had higher percentages of impairment compared to both ND and PDD. As expected, ND overall had the lowest proportion of impaired scores. Ordered by frequency of impairment, Fig. 2 shows that the most frequently impaired cognitive domains in DLB were visual attention and processing speed. More than 75% of DLB patients were impaired on trail making tasks, both number sequencing and number-letter switching. An even higher proportion of impairment was seen in PDD, where 100% were impaired on number-letter switching task. Out of all cognitive tests, the number-letter switching task showed the highest level of impaired performances across all three groups, including ND (see Table 4 for full details on percentage of impairment in each diagnostic group). Next, more than 50% of the DLB group had impaired performance on mental processing speed (Coding), visuospatial constructive tasks (both Block design and RCFT copy), and visual memory (RCFT immediate recall). RCFT copy was impaired in 66% of DLB patients, and free recall was impaired in 69%. In comparison, 50% of PDD patients had impaired performance on these tests. Verbal learning and delayed recall (RAVLT learning and delayed recall) was impaired in 44% of DLB patients, while ND generally performed within normal range on both learning and delayed recall. PDD had a higher proportion of impaired performance on delayed recall (38%) compared to learning (17%), but it should be noted that the learning trial was missing for two PDD participants. Semantic memory and general knowledge (Information), auditive short-term memory and working memory (Digit span), abstract verbal thinking (Similarities), and arithmetic ability (Arithmetic) were impaired in less than a third of DLB patients, and logical thinking (Matrix reasoning) was impaired in 35%, meaning that a significant proportion of patients performed within the normal range on these cognitive tests. In comparison, 40% of PDD participants were impaired on Arithmetic, and 50% on Matrix reasoning. For completeness of information, we followed visual inspection with statistical group comparisons. Despite the reduced statistical power in the smaller subsample with neuropsychological data, we obtained a statistically significant difference between DLB and ND on Block design (p = 0.011) and verbal learning on RAVLT (p = 0.009), which were both more frequently impaired in DLB. There were no other significant group differences on the other reported neuropsychological tests (p > 0.05). Table 4 Neuropsychological test performance Variable DLB = 43 N PDD = 9 N ND = 11 N Age at NP 71.4 (7.0) 43 64.8 (6.7) 9 68.7 (7.6) 11 Education 12.4 (3.2) 43 11.3 (3.4) 9 14.7 (3.6) 11 RAVLT learning 17 (44%) 39 1 (17%) 6 0 (0%) 10 RAVLT 30 min 17 (44%) 39 3 (38%) 8 1 (10%) 10 RCFT copy 21 (66%) 32 3 (50%) 6 3 (33%) 9 RCFT recall 20 (69%) 29 3 (50%) 6 3 (30%) 10 Information 3 (8%) 37 2 (29%) 7 0 (0%) 8 Similarities 10 (27%) 37 1 (13%) 8 0 (0%) 9 Block design 24 (59%) 41 3 (43%) 7 1 (10%) 10 Matrix reasoning 7 (35%) 20 2 (50%) 4 1 (11%) 9 Arithmetic 7 (32%) 22 2 (40%) 5 1 (14%) 7 Digit span 10 (25%) 40 1 (17%) 6 0 (0%) 9 Coding 17 (53%) 32 3 (43%) 7 1 (13%) 8 TMT numbers 19 (76%) 25 3 (75%) 4 1 (25%) 4 TMT Let/num 17 (77%) 22 4 (100%) 4 2 (40%) 5 Data is presented as count and percentage with impaired performance on each neuropsychological test, stratified by diagnostic group: DLB = Dementia with Lewy Bodies. PDD = Parkinson’s Disease Dementia. ND = Non-Dementia group (composed of patients with Parkinson’s disease). NP = Neuropsychological assessment. RAVLT = Rey Auditory Verbal Learning Test. RCFT = Rey Complex Figure Test. TMT numbers = Trail Making Test number sequencing. TMT Letter/numbers = Trail Making Test letters and numbers switching. 4. Discussion Our main goal was to describe a naturalistic cohort of patients presenting with clinical features of DLB to a specialized cognitive clinic. We describe the diagnostic procedure and report baseline demographic data and neuropsychological profiles. 143 patients were included. 88 patients had a final diagnosis of DLB, while 35 had PDD, 14 MCI, and six patients had other types of dementia. There were no statistically significant differences in frequency of any core clinical features between DLB and PDD. However, amyloid positivity as measured in CSF was significantly more frequent in DLB than in PDD. The Non-Dementia group was heterogenous and included participants with MCI-PD, MCI-LB and MCI without specified cause. Visual hallucinations were less frequent in ND participants compared to both DLB and PDD. Clinical diagnostic challenges Out of 143 patients presenting with core clinical features of DLB, 88 fulfilled criteria for probable or possible DLB. A majority of the non-DLB patients had PD-related cognitive impairment, i.e. PDD or PD-MCI. While most of these PD-patients had been diagnosed with PD prior to seeking the cognitive clinic, there may still be challenges in the diagnostic procedure. The average time from PD diagnosis to PDD onset has been reported to be approximately 10 years ( 36 ). An aggressive and faster progression of cognitive decline may raise suspicion of DLB. Some patients or caregivers retrospectively report the onset of cognitive impairment to have been simultaneous or prior to the parkinsonian features, and others receive a diagnosis of dementia closely after the 1-year mark, making it difficult to determine the exact time of dementia onset. As we carefully reviewed cases retrospectively to confirm the final diagnosis, we strictly employed the 1-year rule to properly differentiate DLB from PDD (McKeith et al 2017). Additionally, the clinical separation of DLB from AD may be challenging as well. While the proportion of patients receiving a clinical diagnosis of AD was only around 1% in this cohort, some patients had been given a clinical diagnosis of both AD and DLB. When inspecting clinical records in this cohort, we also observed that some patients had received a previous clinical AD diagnosis which was later converted to DLB when core clinical features were unveiled or became more prominent. This phenomenon may reflect the diagnostic difficulties in separating DLB from AD. Previous studies have reported that around 50% of DLB patients show evidence for amyloid-related pathology ( 5 , 7 ). In our cohort, only 27% of DLB patients were amyloid-positive in CSF. It is possible that this could be explained by DLB patients being misdiagnosed with AD and therefore not included in this cohort. While including patients having two clinical diagnoses of both DLB and AD may complicate specific conclusions for DLB, excluding these patients would limit generalizability to a clinical context. Additionally, if national registers and databases only consider one ICD-10 code to be the primary etiology, the coding of double etiologies may influence the statistics and underestimate the number of DLB patients. Frequency of core clinical features Overall, parkinsonism was the most common core clinical feature across all diagnostic groups in the Find-DLB cohort. 90% of DLB patients had at least one cardinal feature of spontaneous parkinsonism. While we did not stratify for different features of parkinsonism, previous studies have found rigidity and bradykinesia in up to 85% of DLB patients, with lower prevalence of resting tremors ( 37 ). Visual hallucinations were present in almost 70% of DLB patients, in line with previous reports ( 14 , 37 , 38 ). Probable RBD was the least frequent core feature in our DLB group occurring in 46% of patients, and generally less occurring than in other DLB cohorts which have found RBD to be present in about 76% of neuropathologically confirmed cases ( 38 ). The lower frequency of probable RBD in our cohort may thus be related to the lack of a bed partner to report RDB-related symptoms as well as the lack of polysomnography. Furthermore, the least documented symptom in health records in our cohort was cognitive fluctuations, which has long been considered a difficult symptom to capture ( 39 ). Cognitive fluctuations may be difficult to define and explain to the patient and caregiver. The prospective collection of cases in the Find-DLB cohort has thus included validated questionnaires for probable RBD ( 40 ), and a clinical rating scale for fluctuations ( 41 ). Hence, in the future we will be able to compare the prospective rates with those in the current report based mostly on retrospective cases. The “cognitive profile” of impairment in DLB A majority of DLB patients were impaired on visuospatial constructive tasks, visual memory, and processing speed tasks such as digit symbol and trail making tests. This is in line with previous research, which has found the cognitive profile in DLB to show a larger proportion of visual perceptual, attentional, and executive impairment compared to other cognitive domains ( 1 ). Visual memory impairment in DLB has been shown to be comparable to that of AD ( 42 , 43 ). It is possible that this reflects the visual processing deficit common in DLB influencing the memory encoding process, rather than representing a genuine memory impairment. Interestingly, 44% of DLB patients had impaired verbal learning and delayed free recall. While the memory deficit in DLB has been hypothesized to be partially related to encoding and retrieval deficits rather than memory storage, previous studies found that a relevant portion of DLB patients may have impaired verbal memory storage and consolidation, even at MCI-LB stages ( 42 , 44 ). A limitation of our Find-DLB cohort is the lack of memory recognition subtasks, which would help clarify whether our memory finding is related to encoding and retrieval or memory storage and consolidation. WAIS-subtests Digit span and Arithmetic were impaired in less than a third of DLB patients, meaning that a majority performed within normal range on tasks traditionally considered as working memory processes. Previous research has found working memory to be impaired in DLB, and more severely impaired than in AD ( 43 , 45 ). WAIS-subtest Similarities, measuring abstract thinking and considered partly executive in nature, was also preserved in a large proportion of DLB patients in our cohort. It should be noted that the lower proportion of impaired performances on some neuropsychological tests could be influenced by the selection process of the subgroup with neuropsychological assessment in our cohort. In our clinic, patients with severe impairment on cognitive screening may not undergo neuropsychological assessment and thus, would not be included in these analyses. When comparing DLB with PDD, visual inspection suggested similar frequencies of impairment on tests such as complex figure copy and recall, as well as trail making tasks. However, PDD had a lower proportion of impaired patients on several neuropsychological tests. Specifically, impairment in verbal learning in PDD was similar to ND and qualitatively milder than that in patients with DLB. Some previous studies have reported differences in memory impairment between PDD and DLB with a trend towards lower learning and memory retention in DLB, while other studies did not find any significant differences ( 9 , 10 ). In our study, the qualitative differences between DLB and PDD in cognitive performance are not explained by differences in global cognitive performance as reflected by the MMSE. As expected, ND generally had a smaller proportion of impaired performances on most tests, compared to both DLB and PDD. Despite the limited statistical power in the subsample with neuropsychological data available, we followed visual inspection of percentage of impairment with formal statistical testing for completeness of information. We found that verbal learning from RAVLT and Block design from WAIS were statistically significantly more frequently impaired in DLB than in ND. We did not capture any other statistically significant results, likely because of the small sample size of the PDD and ND groups. In summary, cognitive impairment in our DLB patients was primarily characterized by impairment in visuospatial constructive tasks, visual memory, visual attention and processing speed, as well as executive functions as measured by task switching. The profile is in line with previous reports of commonly affected domains in DLB ( 1 ). Auditory short term- and working memory tasks were less frequently impaired in our DLB group. Limitations This study has some limitations. Due to the clinical nature of the data, some variables were incomplete and the diagnostic battery for each patient may differ. This may increase the risk of bias, such as within the context of neuropsychological assessment - patients with severe cognitive impairment may be less likely to undergo full neuropsychological evaluation. However, the bias may be less than in research-oriented cohorts that often recruit DLB patients at mild to moderate stages. Furthermore, the small sizes of PDD and ND groups likely limited the possibility to obtain more statistically significant differences in neuropsychological variables. We circumvented this by using normative data and reporting frequencies of impairment across tests as the main analyses, while statistical comparisons were explorative and reported for completeness of information. The selection of norms was made carefully since norms may affect the interpretation of what constitutes an impairment. Further, the chosen norms are applied in the clinic, which improves generalizability to a clinical context. In our study, all norms were age-stratified and, on several tests, norms also took gender and education into account. Age, gender, and education are factors known to influence performance on some cognitive tests. Lastly, we included patients with possible DLB as well as patients with a concurrent clinical diagnosis of DLB and AD, since our aim was to present a realistic and naturalistic clinical cohort. However, whether the frequency of cognitive impairments differs across probable DLB, possible DLB, and DLB cases with a clinical phenotype of mixed AD and DLB should be investigated further. 5. Conclusion This article describes the Find-DLB cohort, a cohort of patients presenting with clinical features of DLB to our specialized cognitive clinic, in a naturalistic manner. Our study shows that even with access to several diagnostic modalities, diagnosing DLB is challenging within the clinical context. Patients are seeking cognitive evaluation at an earlier stage than before and there is an increasing need to provide more precise diagnostic and prognostic information. The diagnostic process from first visit to primary care physician to a DLB diagnosis is time and resource consuming, both for the health care system and the patient and caregiver. More research should investigate this process and identify the factors susceptible for improvement. The core clinical features are the foundation of the diagnostic process in DLB, and while parkinsonism and visual hallucinations may be more obvious during the clinical assessment, cognitive fluctuations and RBD can be more dubious. Moving forward, the evaluation of these features would benefit from a more systematic data collection using validated clinical rating instruments. Abbreviations AD Alzheimer’s Disease ADL Activities of Daily Living CSF Cerebrospinal Fluid CT Computer TomographyD-KEFS:Delis–Kaplan Executive Function System DAT-Scan Dopamine Transporter Scan DLB Dementia with Lewy Bodies EEG Electroencephalography EOD Early Onset Dementia FDG Fluorodeoxyglucose ICD-10 International Statistical Classification of Diseases and Related Health Problems 10th Revision MCI Mild Cognitive Impairment MCI-LB MCI with Lewy bodies MMSE Mini Mental State Examination MoCA Montreal Cognitive Assessment MRI Magnetic Resonance Imaging ND Non-Dementia PDD Parkinsons Disease with dementia PD Parkinsons Disease PD-MCI MCI due to PD PET Positron Emission Tomography p-tau Phosphorylated tau RAVLT Rey Auditory Verbal Learning Test RBD REM-sleep Behavior Disorder RCFT Rey Complex Figure Test TMT Trail Making Test WAIS Wechsler Adult Intelligence Scale Declarations Ethics approval Data has been handled in accordance with GDPR legislation. The study was approved by the Regional Ethics Committee in Stockholm (Dnr: 2013/2169-31) and the following amendments were approved by the Swedish Ethical Review Authority,Uppsala (Dnr: 2019-05978, and 2022-01251-02). This study was carried out in compliance with the Declaration of Helsinki. Consent to participate All included patients provided signed written consent. Competing interests DF consults for BioArctic and has received honoraria from Esteve Pharmaceuticals S.A. All other authors declared no competing interests. Clinical Trial Number Not applicable Availability of data and materials The data that supports the findings of this study are not publicly available due to privacy and are protected by a pseudonymization protocol. Data may be available upon reasonable request from the corresponding author if legal and ethical requirements are met. Funding DF receives funding from the Swedish Research Council (Vetenskapsrådet, grant 2022-00916), the Center for Innovative Medicine (CIMED, grants 20200505 and FoUI-988826), the regional agreement on medical training and clinical research of Stockholm Region (ALF Medicine, grants FoUI-962240 and FoUI-987534), the Swedish Brain Foundation (Hjärnfonden FO2023-0261, FO2022-0175, FO2021-0131), the Swedish Alzheimer Foundation (Alzheimerfonden AF-968032, AF-980580, AF-994058, AF-1010553), the Swedish Dementia Foundation (Demensfonden), the Gamla Tjänarinnor Foundation, the Gun och Bertil Stohnes Foundation, the Åke Wiberg Foundation, StratNeuro, Parkinsonfonden, Funding for Research from Karolinska Institutet, Neurofonden, and the Foundation for Geriatric Diseases at Karolinska Institutet, contributions from private bequests and academic agreements with industry. Authors' contributions SG performed analyses and drafted the manuscript. VJ, SGP, NB, AN and AB contributed to patient recruitment/data acquisition. SG, VJ, and DF contributed to the overall design of the project and AR contributed to statistical design. AN, TG and DF contributed to the funding for the project. DF provided overall supervision. All authors contributed to reading and editing of the manuscript. Acknowledgements The authors would like to extend their gratitude to the patients who participated in this project, as well as the healthcare providers who facilitated the project. References McKeith IG, Boeve BF, Dickson DW, Halliday G, Taylor JP, Weintraub D et al (2017) Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. Neurology 89(1):88–100 Hogan DB, Fiest KM, Roberts JI, Maxwell CJ, Dykeman J, Pringsheim T et al (2016) The Prevalence and Incidence of Dementia with Lewy Bodies: a Systematic Review. Can J Neurol Sci 43(Suppl 1):S83–95 Vann Jones SA, O'Brien JT (2014) The prevalence and incidence of dementia with Lewy bodies: a systematic review of population and clinical studies. Psychol Med 44(4):673–683 Kane JPM, Surendranathan A, Bentley A, Barker SAH, Taylor JP, Thomas AJ et al (2018) Clinical prevalence of Lewy body dementia. Alzheimers Res Ther 10(1):19 Kantarci K, Lowe VJ, Chen Q, Przybelski SA, Lesnick TG, Schwarz CG et al (2020) β-Amyloid PET and neuropathology in dementia with Lewy bodies. Neurology 94(3):e282–e91 Robinson JL, Xie SX, Baer DR, Suh E, Van Deerlin VM, Loh NJ et al (2023) Pathological combinations in neurodegenerative disease are heterogeneous and disease-associated. Brain 146(6):2557–2569 Irwin DJ, Grossman M, Weintraub D, Hurtig HI, Duda JE, Xie SX et al (2017) Neuropathological and genetic correlates of survival and dementia onset in synucleinopathies: a retrospective analysis. Lancet Neurol 16(1):55–65 Merdes AR, Hansen LA, Jeste DV, Galasko D, Hofstetter CR, Ho GJ et al (2003) Influence of Alzheimer pathology on clinical diagnostic accuracy in dementia with Lewy bodies. Neurology 60(10):1586–1590 Aldridge GM, Birnschein A, Denburg NL, Narayanan NS (2018) Parkinson's Disease Dementia and Dementia with Lewy Bodies Have Similar Neuropsychological Profiles. Front Neurol 9:123 Filoteo JV, Salmon DP, Schiehser DM, Kane AE, Hamilton JM, Rilling LM et al (2009) Verbal learning and memory in patients with dementia with Lewy bodies or Parkinson's disease with dementia. J Clin Exp Neuropsychol 31(7):823–834 van de Beek M, van Steenoven I, van der Zande JJ, Porcelijn I, Barkhof F, Stam CJ et al (2021) Characterization of symptoms and determinants of disease burden in dementia with Lewy bodies: DEvELOP design and baseline results. Alzheimers Res Ther 13(1):53 Roberts RO, Geda YE, Knopman DS, Cha RH, Pankratz VS, Boeve BF et al (2008) The Mayo Clinic Study of Aging: design and sampling, participation, baseline measures and sample characteristics. Neuroepidemiology 30(1):58–69 Elder GJ, Colloby SJ, Lett DJ, O'Brien JT, Anderson KN, Burn DJ et al (2016) Depressive symptoms are associated with daytime sleepiness and subjective sleep quality in dementia with Lewy bodies. Int J Geriatr Psychiatry 31(7):765–770 Naharci MI, Kayahan Satis N, Ozsurekci C, Tasci I (2023) Assessment of clinical features and coexisting geriatric syndromes in newly diagnosed dementia with Lewy bodies: a retrospective study in a tertiary geriatrics setting in Turkey. Eur Geriatr Med 14(1):19–27 Statistics Sweden Population density per sq. km, population and land area by region and sex 2023 [Available from: https://www.statistikdatabasen.scb.se/pxweb/en/ssd/START__BE__BE0101__BE0101C/BefArealTathetKon/ Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I et al (2005) The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 53(4):695–699 Folstein MF, Folstein SE, McHugh PR (1975) Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12(3):189–198 Storey JE, Rowland JT, Basic D, Conforti DA, Dickson HG (2004) The Rowland Universal Dementia Assessment Scale (RUDAS): a multicultural cognitive assessment scale. Int Psychogeriatr 16(1):13–31 Winblad B, Palmer K, Kivipelto M, Jelic V, Fratiglioni L, Wahlund LO et al (2004) Mild cognitive impairment–beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med 256(3):240–246 Litvan I, Goldman JG, Tröster AI, Schmand BA, Weintraub D, Petersen RC et al (2012) Diagnostic criteria for mild cognitive impairment in Parkinson's disease: Movement Disorder Society Task Force guidelines. Mov Disord 27(3):349–356 McKeith IG, Ferman TJ, Thomas AJ, Blanc F, Boeve BF, Fujishiro H et al (2020) Research criteria for the diagnosis of prodromal dementia with Lewy bodies. Neurology 94(17):743–755 Wechsler D (2008) Wechsler Adult Intelligence Scale- Fourth Edition: Technical and interpretive manual, 4th edn. Pearson, San Antonio Wechsler D (1997) Wechsler Adult Intelligence Scale, 3rd edn. The Psychological Corporation, San Antonio Rey A (1958) L'examen clinique en psychologie. [The clinical examination in psychology]. Presses Universitaries De France, Oxford, England, pp 222–p Rey A (1941) L'examen psychologique dans les cas d'encéphalopathie traumatique. (Les problems.). [The psychological examination in cases of traumatic encepholopathy. Probl ] Archives de Psychologie 28:215–285 Reitan RM (1955) The relation of the trail making test to organic brain damage. J Consult Psychol 19(5):393–394 Delis D (2001) Delis-Kaplan Executive Function System. The Psychological Corporation Bergman I, Almkvist O (2015) Neuropsychological test norms controlled for physical health: Does it matter? Scand J Psychol 56(2):140–150 Petersen RC (2004) Mild cognitive impairment as a diagnostic entity. J Intern Med 256(3):183–194 Ekman U, Ferreira D, Muehlboeck JS, Wallert J, Rennie A, Eriksdotter M et al (2020) The MemClin project: a prospective multi memory clinics study targeting early stages of cognitive impairment. BMC Geriatr 20(1):93 Rennie A, Ekman U, Shams S, Rydén L, Samuelsson J, Zettergren A et al (2024) Cerebrovascular and Alzheimer’s disease biomarkers in dementia with Lewy bodies and other dementias. Brain Commun. ;6(5) Ferreira D, Jelic V, Cavallin L, Oeksengaard AR, Snaedal J, Høgh P et al (2016) Electroencephalography Is a Good Complement to Currently Established Dementia Biomarkers. Dement Geriatr Cogn Disord 42(1–2):80–92 Ferreira D, Bartrés-Faz D, Nygren L, Rundkvist LJ, Molina Y, Machado A et al (2016) Different reserve proxies confer overlapping and unique endurance to cortical thinning in healthy middle-aged adults. Behav Brain Res 311:375–383 Correia R, Nieto A, Ferreira D, Sabucedo M, Barroso J (2015) Fund of Information is More Strongly Associated with Neuropsychological Functioning Than Education in Older Spanish Adults. Arch Clin Neuropsychol 30(4):310–321 van Steenoven I, Aarsland D, Hurtig H, Chen-Plotkin A, Duda JE, Rick J et al (2014) Conversion between mini-mental state examination, montreal cognitive assessment, and dementia rating scale-2 scores in Parkinson's disease. Mov Disord 29(14):1809–1815 Aarsland D, Creese B, Politis M, Chaudhuri KR, ffytche DH, Weintraub D, Ballard C (2017) Cognitive decline in Parkinson disease. Nat Reviews Neurol 13(4):217–231 Prasad S, Katta MR, Abhishek S, Sridhar R, Valisekka SS, Hameed M et al (2023) Recent advances in Lewy body dementia: A comprehensive review. Dis Mon 69(5):101441 Ferman TJ, Boeve BF, Smith GE, Lin SC, Silber MH, Pedraza O et al (2011) Inclusion of RBD improves the diagnostic classification of dementia with Lewy bodies. Neurology 77(9):875–882 Ballard CG (2004) Definition and diagnosis of dementia with Lewy bodies. Dement Geriatr Cogn Disord 17(Suppl 1):15–24 Boeve BF, Molano JR, Ferman TJ, Lin SC, Bieniek K, Tippmann-Peikert M et al (2013) Validation of the Mayo Sleep Questionnaire to screen for REM sleep behavior disorder in a community-based sample. J Clin Sleep Med 9(5):475–480 Ferman TJ, Smith GE, Boeve BF, Ivnik RJ, Petersen RC, Knopman D et al (2004) DLB fluctuations: specific features that reliably differentiate DLB from AD and normal aging. Neurology 62(2):181–187 Querry M, Blanc F, Bousiges O, Philippi N, Cretin B, Demuynck C et al (2023) Memory Outcome in Prodromal and Mild Dementia with Lewy Bodies and Alzheimer's Disease: A Longitudinal Study. J Alzheimers Dis 94(1):147–162 Oda H, Yamamoto Y, Maeda K (2009) The neuropsychological profile in dementia with Lewy bodies and Alzheimer's disease. Int J Geriatr Psychiatry 24(2):125–131 Kemp J, Philippi N, Phillipps C, Botzung A, Blanc F (2017) Cognitive profile in prodromal disease (dementia) with Lewy bodies. Geriatr Psychol Neuropsychiatr Vieil 15(4):434–442 Macoir J (2022) The Cognitive and Language Profile of Dementia with Lewy Bodies. Am J Alzheimer's Disease Other Dementias® 37:15333175221106901 Additional Declarations The authors declare potential competing interests as follows: DF consults for BioArctic and has received honoraria from Esteve Pharmaceuticals S.A. All other authors declared no competing interests. 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-7865542","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":529917585,"identity":"0ee0ca70-87bc-42b5-99b0-6bb5fc15a5f7","order_by":0,"name":"Stephanie Gravett","email":"","orcid":"https://orcid.org/0009-0006-1924-3960","institution":"Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden, and Theme Women’s Health and Allied Health Professionals, Karolinska University Hospital, Stockholm, Sweden","correspondingAuthor":false,"prefix":"","firstName":"Stephanie","middleName":"","lastName":"Gravett","suffix":""},{"id":529923468,"identity":"7f176d1b-cec8-43ca-855d-6ffceef49fd3","order_by":1,"name":"Sara Garcia-Ptacek","email":"","orcid":"","institution":"Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden, and Theme Inflammation and Aging, Karolinska University Hospital, Stockholm, Sweden","correspondingAuthor":false,"prefix":"","firstName":"Sara","middleName":"","lastName":"Garcia-Ptacek","suffix":""},{"id":529923469,"identity":"a4038c6a-4228-4ebf-a559-544b973d0a5a","order_by":2,"name":"Anna Rennie","email":"","orcid":"","institution":"Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden","correspondingAuthor":false,"prefix":"","firstName":"Anna","middleName":"","lastName":"Rennie","suffix":""},{"id":529923470,"identity":"1d370aaf-0317-4932-aff4-9ff875a21241","order_by":3,"name":"Nenad Bogdanovic","email":"","orcid":"","institution":"Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden, and Theme Inflammation and Aging, Karolinska University Hospital, Stockholm, Sweden","correspondingAuthor":false,"prefix":"","firstName":"Nenad","middleName":"","lastName":"Bogdanovic","suffix":""},{"id":529923471,"identity":"314f8fe6-7e2c-494c-b951-fb07f11feb2c","order_by":4,"name":"Alexandre Bonnard","email":"","orcid":"","institution":"Theme Inflammation and Aging, Karolinska University Hospital, Stockholm, Sweden","correspondingAuthor":false,"prefix":"","firstName":"Alexandre","middleName":"","lastName":"Bonnard","suffix":""},{"id":529923472,"identity":"ad4e6b42-7d48-4dc2-a4c5-a49d83193721","order_by":5,"name":"Tobias Granberg","email":"","orcid":"","institution":"Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden, and Department of Neuroradiology, Karolinska University Hospital, Stockholm, Sweden","correspondingAuthor":false,"prefix":"","firstName":"Tobias","middleName":"","lastName":"Granberg","suffix":""},{"id":529923473,"identity":"2bbedabd-c5f9-4489-9fe7-990fcbdac579","order_by":6,"name":"Agneta Nordberg","email":"","orcid":"","institution":"Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden, and Theme Inflammation and Aging, Karolinska University Hospital, Stockholm, Sweden","correspondingAuthor":false,"prefix":"","firstName":"Agneta","middleName":"","lastName":"Nordberg","suffix":""},{"id":529923474,"identity":"32261abf-c075-4eac-b485-84fbc0895c9a","order_by":7,"name":"Vesna Jelic","email":"","orcid":"","institution":"Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden, and Theme Inflammation and Aging, Karolinska University Hospital, Stockholm, Sweden","correspondingAuthor":false,"prefix":"","firstName":"Vesna","middleName":"","lastName":"Jelic","suffix":""},{"id":529923475,"identity":"a1e11124-c19c-48aa-86b6-2f7b27472248","order_by":8,"name":"Daniel Ferreira","email":"data:image/png;base64,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","orcid":"","institution":"Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden, and Facultad de Ciencias de la Salud, Universidad Fernando Pessoa Canarias, Las Palmas de Gran Canaria, España","correspondingAuthor":true,"prefix":"","firstName":"Daniel","middleName":"","lastName":"Ferreira","suffix":""}],"badges":[],"createdAt":"2025-10-15 08:23:09","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":true,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-7865542/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7865542/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":93778196,"identity":"4b7f0266-8082-4080-a7f8-007f9449cd92","added_by":"auto","created_at":"2025-10-17 12:46:01","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":239226,"visible":true,"origin":"","legend":"","description":"","filename":"ManuscriptFindDLBPreprint.docx","url":"https://assets-eu.researchsquare.com/files/rs-7865542/v1/6b2cb1135e66b2e57c08360c.docx"},{"id":93778195,"identity":"a178714d-e1d6-463f-81d9-21d5e1478ab6","added_by":"auto","created_at":"2025-10-17 12:46:01","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":342,"visible":true,"origin":"","legend":"","description":"","filename":"rs7865542.json","url":"https://assets-eu.researchsquare.com/files/rs-7865542/v1/25e48abad340697b93c3e966.json"},{"id":93779884,"identity":"fb2d8570-9683-4a4c-9195-856c9c44148c","added_by":"auto","created_at":"2025-10-17 12:54:01","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":144754,"visible":true,"origin":"","legend":"","description":"","filename":"rs78655420enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-7865542/v1/016a7873ad5037425abe72e1.xml"},{"id":93779883,"identity":"503a61d8-8c78-4d48-8a4f-b0247627751f","added_by":"auto","created_at":"2025-10-17 12:54:01","extension":"png","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":29760,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7865542/v1/fcfe91f4de00be8729976d1d.png"},{"id":93778194,"identity":"774ed134-ca5f-45a5-bd7c-7525a93048a3","added_by":"auto","created_at":"2025-10-17 12:46:01","extension":"png","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":11689,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7865542/v1/dc61edc95766d89704832f8d.png"},{"id":93778198,"identity":"7e48d1a5-5b26-4d4d-9a98-77566a32db1c","added_by":"auto","created_at":"2025-10-17 12:46:01","extension":"xml","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":142191,"visible":true,"origin":"","legend":"","description":"","filename":"rs78655420structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7865542/v1/12300ae5820a9e71cec66a3e.xml"},{"id":93778199,"identity":"ec8d8b11-2f24-48ca-8770-97c526a9706a","added_by":"auto","created_at":"2025-10-17 12:46:01","extension":"html","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":151633,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7865542/v1/8c05bca0c93e101781af202d.html"},{"id":93778191,"identity":"deff18ab-71d9-412b-b56a-07b2a859f1c3","added_by":"auto","created_at":"2025-10-17 12:46:01","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":83003,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of the evaluation process at the Karolinska University Hospital Huddinge Cognitive clinic\u003c/p\u003e\n\u003cp\u003eCT = Computer Tomography. MRI = Magnetic Resonance Imaging. FDG = Fluorodeoxyglucose. PET = Positron Emission Tomography. EEG = Electroencephalography. DAT-Scan = Dopamine Transporter Scan. EOD = Early Onset Dementia. MCI = Mild Cognitive Impairment (referring to MCI with high risk of conversion to dementia).\u003c/p\u003e","description":"","filename":"floatimage117.png","url":"https://assets-eu.researchsquare.com/files/rs-7865542/v1/1d7876e3b136ea20e737ebaa.png"},{"id":93778192,"identity":"a5a3105f-e2da-45ba-81a1-ff5ea32d997d","added_by":"auto","created_at":"2025-10-17 12:46:01","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":40762,"visible":true,"origin":"","legend":"\u003cp\u003eNeuropsychological profile of impairment\u003c/p\u003e\n\u003cp\u003eX-axis shows neuropsychological tests (NP), and Y-axis shows percentage of participants with impaired performance on each test. DLB = Dementia with Lewy Bodies. PDD = Parkinson’s Disease Dementia. ND = Non-Dementia group (composed of patients with Parkinson’s disease). RAVLT = Rey Auditory Verbal Learning Test. RCFT = Rey Complex Figure Test. TMT numbers = Trail Making Test number sequencing. TMT Letter/numbers = Trail Making Test letters and numbers switching.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7865542/v1/6b21449ac9bdea7a008064ef.png"},{"id":93780238,"identity":"2a33ef47-1400-4183-bf4f-0596c49cfa5e","added_by":"auto","created_at":"2025-10-17 13:02:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1038325,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7865542/v1/d24b3736-12f3-477e-818d-e0471e61872d.pdf"}],"financialInterests":"The authors declare potential competing interests as follows: DF consults for BioArctic and has received honoraria from Esteve Pharmaceuticals S.A. All other authors declared no competing interests. ","formattedTitle":"\u003cp\u003e\u003cstrong\u003eFind-DLB - A naturalistic cohort of patients presenting with clinical features of Dementia with Lewy bodies to a specialized cognitive clinic\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Key summary points","content":"\u003cp\u003e\u003cstrong\u003eAim:\u0026nbsp;\u003c/strong\u003eWe aimed to characterize a naturalistic cohort of patients with symptoms of Dementia with Lewy Bodies (DLB).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFindings:\u0026nbsp;\u003c/strong\u003eWhile the majority (88/143) received a clinical diagnosis of DLB, 33 patients received a diagnosis of Parkinson\u0026rsquo;s disease dementia, and 22 patients received a diagnosis of Mild cognitive impairment or other dementia. Parkinsonism was the most frequent core feature, and DLB patients commonly showed impairment in visuospatial, attentional, executive, and visual memory tasks.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMessage:\u0026nbsp;\u003c/strong\u003eThe differential diagnosis of DLB is challenging in a clinical setting due to overlapping features and requires careful review of clinical features and biomarkers.\u0026nbsp;\u003c/p\u003e"},{"header":"1. Background","content":"\u003cp\u003eDementia with Lewy bodies (DLB) is a common neurodegenerative cause of dementia, characterized by core clinical features of parkinsonism, visual hallucinations, cognitive fluctuations, and REM-sleep behavior disorder (RBD) (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). A previous systematic review reported DLB to account for about 5% of dementia cases, although prevalence values ranged from 0.3 to 24.4% (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). This wide range highlights differences between cohorts and disparities in how DLB is diagnosed and participants recruited to studies across the globe. Indeed, DLB is known to be under-diagnosed, and differences in prevalence rates in specialized clinics may be influenced by factors such as sensitivity to core clinical features, education or training of clinical staff, and research focus of specific centers (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). One reason for the diagnostic challenges is the significant overlap between DLB and other disorders such as Alzheimer\u0026rsquo;s disease (AD), Parkinson\u0026rsquo;s disease with dementia (PDD), and cerebrovascular disease. While clinical presentations may converge, there is also pathological overlap. Around 50% of DLB patients have concomitant AD pathology (\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). This concomitant AD pathology and positivity of AD biomarkers confound the diagnostic accuracy in DLB (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Additionally, there are challenges differentiating DLB from PDD, especially when cognitive impairment progresses rapidly and occurs early during Parkinsons disease (PD).\u003c/p\u003e\u003cp\u003eCognitive profiling with neuropsychological assessment is an important diagnostic tool within dementia evaluation to differentiate level and type of cognitive impairment. The cognitive profile in DLB generally constitutes impairment in visual processing, attention and executive functions with relative sparing of memory and naming, differentiating it from AD (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). The differences in the cognitive profile of DLB versus PDD have been partially explored but results are not conclusive (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eWhile several DLB cohorts have been well characterized, these cohorts were primarily research-oriented (\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e), so that study participants may be different than those presenting at specialized cognitive clinics. There are fewer publications of naturalistic clinical cohorts describing DLB patients (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e), and the clinical journey of patients presenting to the cognitive clinic with a suspicion of DLB is generally not reported and largely unknown. Investigating this patient group is thus relevant to capturing a more complete picture of DLB and understand potential bias in the reported profiles of patients eventually being recruited to well-characterized research-oriented cohorts.\u003c/p\u003e\u003cp\u003eThe current study describes Find-DLB, a naturalistic clinical cohort of patients presenting with clinical features of DLB to a specialized cognitive clinic. The goal was to present a realistic view of the diagnostic flow, which may help increase the knowledge on the day-to-day challenges clinicians face when differentiating DLB from other neurodegenerative diseases, non-degenerative causes of cognitive impairment such as psychiatric illnesses, and normal ageing. We aimed to present baseline demographic, biomarker, and neuropsychological data of the original cohort as well as stratified by diagnostic group after classification in naturalistic clinical rounds.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cp\u003e\u003cb\u003eStudy setting\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe Cognitive clinic at Karolinska University Hospital Huddinge is a specialist unit for cognitive disorders. Patients are referred from their primary care facility or occasionally from other specialist units on suspicion of cognitive disorder. Approximately 600 referrals are accepted each year. Both suspected early onset (\u0026lt;\u0026thinsp;65y) and late onset (\u0026gt;\u0026thinsp;65y) patients are evaluated at the clinic. Patients\u0026thinsp;\u0026gt;\u0026thinsp;65y are usually from the close geographical area, while\u0026thinsp;\u0026lt;\u0026thinsp;65y patients may be referred from the entire Stockholm Region, which comprises several municipalities over an area of approximately 6500 square km, with a population of 2 450 000 in 2023 (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Second opinions may be referred from other Swedish regions across the country as well.\u003c/p\u003e\u003cp\u003ePrior to referral, most patients have undergone a basic dementia evaluation in primary care, often including a computer tomography (CT) scan or magnetic resonance imaging (MRI) of the brain, blood sampling, assessment of activities of daily living (ADL), as well as cognitive screening with the Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), or the Rowland Universal Dementia Assessment Scale (RUDAS) (\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). As reported in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, the specialist dementia evaluation can include a range of clinical assessments, neuroimaging modalities, and lumbar puncture depending on clinical suspicion. Diagnoses are determined at multi professional rounds comprised of 4\u0026ndash;10 people, including physician, neuropsychologist, nurse, occupational therapist, and speech and language pathologist. All relevant information from the examinations is presented and diagnosis is determined by consensus principle. The ICD-10 is used for diagnostic coding. Patients are often subject to follow up at the clinic, and they may therefore repeat some evaluations. Assessments might be added by the responsible physician during follow-up to help differentiate the diagnosis in complex cases. The full process is illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cb\u003eParticipants\u003c/b\u003e\u003c/p\u003e\u003cp\u003eFind-DLB was started in 2020 with the main goal of improving detection of DLB in specialized cognitive clinics in Stockholm, Sweden. Find-DLB includes a retrospective and a prospective approach, including retrospective patients up to 2020, and recruiting patients prospectively from 2020. Patients were considered for inclusion if there was suspicion of any core clinical features of DLB, namely visual hallucinations, parkinsonism, cognitive fluctuations or probable RBD. Some patients were included upon their first doctor\u0026rsquo;s visit, while other patients were retrospectively recruited at follow up after receiving their diagnosis. Patients are excluded from Find-DLB if they terminated their evaluation before receiving a diagnosis at diagnostic rounds.\u003c/p\u003e\u003cp\u003e\u003cb\u003eDiagnostic procedure\u003c/b\u003e\u003c/p\u003e\u003cp\u003e Find-DLB being a naturalistic project, the procedure during diagnostic rounds follows the general Swedish guidelines of current clinical criteria. For research purposes, clinical diagnoses were retrospectively cross checked with the 2017 consensus criteria for DLB (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) by a senior physician (V.J.) and a neuropsychologist (S.G.) together. Mild cognitive impairment (MCI) was diagnosed in accordance with consensus criteria, if there is objective cognitive impairment on neuropsychological tests with relatively spared level of function in ADL (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Additional criteria were applied to establish the diagnosis of MCI due to PD (PD-MCI) (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) or MCI with Lewy bodies (MCI-LB) (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). For patients who presented to the clinic with parkinsonism, the 1-year rule of onset between parkinsonism and dementia was applied to differentiate between DLB and PD (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Unclear cases were retrospectively reviewed by a senior physician (V.J.), who decided the final diagnosis based on all available information. Patients with two clinical diagnoses, i.e. both a diagnosis of AD and DLB, were included in the DLB group for the purpose of the current study.\u003c/p\u003e\u003cp\u003e\u003cb\u003eAssessments\u003c/b\u003e\u003c/p\u003e\u003cp\u003eClinical features\u003c/p\u003e\u003cp\u003eClinical data regarding DLB core clinical features was collected through the electronic health records. Self-, caregiver-, and clinician-reported symptoms were all considered. Parkinsonism was coded as present if the records included descriptions of cardinal parkinsonian features of either bradykinesia, resting tremors, or rigidity. Visual hallucinations were considered present if there was mention of fully formed visual hallucinations. Fluctuations were coded as present if reported as either clear fluctuating cognitive impairment or alertness as well as passing episodes of confusion or delirium. Probable RBD was considered present if there were reported symptoms such as arm flailing, thrashing, punching, screaming or shouting, recurring nightmares, and falling out of bed during sleep time. If a symptom was negated it was coded as not present. If there was no clear mention of a core symptom, it was considered missing data. Several patients reported unspecific symptoms such as visual illusions, presence phenomena, and nightmares without other symptoms of RBD, which were not included in our current analysis.\u003c/p\u003e\u003cp\u003eNeuropsychological assessment\u003c/p\u003e\u003cp\u003eA subgroup of patients (n\u0026thinsp;=\u0026thinsp;96, 67% of the total cohort, n\u0026thinsp;=\u0026thinsp;143) underwent extended neuropsychological evaluations performed by a psychologist. The remaining 47 patients (33%) did not undergo neuropsychological assessment due to low performance on cognitive screening test, severe impairment in ADL, or frailty. Raw data from neuropsychological tests were available for 68 patients (48% of the total cohort) due to failure to submit raw scores in the electronic health records. Most patients underwent neuropsychological assessment within 6 months of their final diagnosis. However, six patients (6%) performed neuropsychological assessment more than two years before their dementia diagnosis. These assessments were carefully reviewed. Based on the available information, five of these patients were included in a group of patients without dementia, referred to below as the Non-Dementia (ND) group. The remaining patient was excluded from further analyses due to insufficient information.\u003c/p\u003e\u003cp\u003eAll neuropsychological tests were administered at a single visit, extending for approximately 2\u0026ndash;3 hours. Since Find-DLB is a fully naturalistic cohort, there was variation in neuropsychological tests used across patients over time. Only tests with scores available for \u0026gt;\u0026thinsp;50% of the subgroup with neuropsychological assessment were included in this article, including the following:\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eVerbal\u003c/strong\u003e\u003cp\u003eWechsler Adult Intelligence Scale 4th edition (WAIS-IV)\u003c/p\u003e\u003c/p\u003e\u003cp\u003e(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) and Wechsler Adult Intelligence Scale 3rd edition (WAIS-III) (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) Subtests: Information, Similarities.\u003c/p\u003e\u003cp\u003e\u003cem\u003eMemory\u003c/em\u003e: Rey Auditory Verbal Learning Test (RAVLT) without distraction list (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e): Total score over 5 learning trials and free delayed recall (30 minutes after learning trials); Rey Complex Figure Test (RCFT), immediate recall.\u003c/p\u003e\u003cp\u003e\u003cem\u003eVisuospatial\u003c/em\u003e: WAIS-IV and WAIS-III Subtests: Block Design, RCFT (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e): Copy trial\u003c/p\u003e\u003cp\u003e\u003cem\u003eExecutive/attention/processing speed\u003c/em\u003e: WAIS-IV and WAIS-III Subtests: Digit Span, Coding, Arithmetic, Matrix reasoning; Trail Making Test A \u0026amp; Trail Making Test B (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e): Time to complete; Delis\u0026ndash;Kaplan Executive Function System (D-KEFS) Trail Making Test 2 \u0026amp; 4 (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e): Standardized score for time to complete.\u003c/p\u003e\u003cp\u003eNeuropsychological raw data was standardized to z-scores using normative data from regression-based norms used in the Cognitive clinic, stratified for age, education, and sex (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). For WAIS and D-KEFS subtests, age-appropriate scaled scores were used.\u003c/p\u003e\u003cp\u003eA total of 57 patients performed subtests from WAIS-IV and 7 patients completed subtests from WAIS-III instead. To facilitate overview of the cognitive functions and domains, corresponding tests from different versions were combined. Specifically, WAIS-III and WAIS-IV standardized scores were combined into single variables for each subtest. Time to complete Trail Making Test A and D-KEFS Trail Making Test 2, as well as Trail Making Test B and D-KEFS Trail Making Test 4, were standardized and combined into two variables: TMT Number sequencing and TMT Letter number switching. For WAIS subtests, strong correlations between WAIS-III and WAIS-IV versions of the subtests have been previously reported, motivating their combination (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). For the Trail Making Test, the placement, number of stimuli and size of the paper differ while the tasks are identical and can, therefore, be combined.\u003c/p\u003e\u003cp\u003eAfter standardization and combination of tests as described above, scores were considered impaired if z-score was \u0026le; -1.5 SD, in accordance with established clinical criteria (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). Discontinuation of a test due to the patient being unable to complete it was considered an impaired test: WAIS-IV Block design was discontinued for one patient, Trail Making Test B for nine patients, D-KEFS Trail Making Test 4 for two patients, and RCFT copy for three patients.\u003c/p\u003e\u003cp\u003eBiomarkers\u003c/p\u003e\u003cp\u003eCerebrospinal fluid (CSF) biomarker status for amyloid-beta 1\u0026ndash;42 and phosphorylated tau 181 (p-tau) was coded as positive or negative if below or above the center-specific cut-off. Since data was collected over a large time span, methods and cut-offs have changed. Due to clinical usefulness and interpretability, data is only presented as positive or negative. The applied cut-offs are described elsewhere(\u003cspan additionalcitationids=\"CR31\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). DaT-scan was coded as positive or negative based on the report from the nuclear medicine department. DaT-scan in one patient was deemed inconclusive, and it was excluded from analysis of group differences. The current article focusses on introducing the Find-DLB cohort and describing the naturalistic diagnostic procedure. Further data beyond the availability of MRI, EEG, and FDG-PET will be presented in future modality-specific publications.\u003c/p\u003e\u003cp\u003e\u003cb\u003eStatistics\u003c/b\u003e\u003c/p\u003e\u003cp\u003eDescriptive data is presented as count and percentage or mean and standard deviation. T-test or ANOVA-test with paired post hoc analyses with the Tukey adjustment were performed on continuous variables. Chi\u0026sup2;- tests were used for categorical variables, and Fisher-Freeman-Halton test was applied when any cell count was \u0026lt;\u0026thinsp;5, with paired post hoc Fisher exact tests. Significance level was pre-determined at p\u0026thinsp;\u0026le;\u0026thinsp;0.05 in all analyses. Years of education were missing for four patients who underwent neuropsychological evaluation. The regression-based norms require years of education to calculate individual predicted values. Out of these four patients, two had information on occupation, and an estimated level of education was derived from the lowest level needed for the registered occupation within the Swedish educational system. For the other two patients, there was insufficient information so that predicted values of education were estimated based on a linear regression model including the raw score of Information from WAIS-IV as a common proxy of educational attainment (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e) along with age, gender, and diagnosis (i.e. DLB, PDD or MCI). MMSE was missing for 39 patients who instead had performed the MoCA-test. An estimated MMSE-score was calculated from MoCA-scores based on a conversion table published elsewhere (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e).\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003e\u003cb\u003eWhole Find-DLB cohort\u003c/b\u003e\u003c/p\u003e\u003cp\u003e144 patients were eligible for inclusion in the Find-DLB cohort. One patient was excluded due to termination of the evaluation prior to a diagnosis. Out of the remaining 143 patients, 88 patients fulfilled criteria for DLB (83 probable DLB and 5 possible DLB), with 8 of them receiving a clinical diagnosis of both DLB and AD. Out of the remaining patients, 35 were diagnosed with PDD; 2 patients fulfilled clinical criteria for AD with atypical presentation such as prominent visuospatial impairment and neuropsychiatric symptoms; and 4 patients were included in the \u0026ldquo;Other dementias\u0026rdquo; group, which included Corticobasal Degeneration and Dementia not otherwise specified. Furthermore, 14 patients received a clinical diagnosis of MCI (8 PD-MCI, 2 MCI-LB, and 4 had an MCI diagnosis without any specified cause) and were included in the Non-Dementia (ND) group. The two AD patients and the \u0026ldquo;Other dementias\u0026rdquo; group were excluded from further analysis due to small group sizes.\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\u003eDemographics and clinical features, Whole cohort (N\u0026thinsp;=\u0026thinsp;143)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMean (SD), or count\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e70.8 (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e142\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex (male)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e102 (71%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e143\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYears of education\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12.3 (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e119\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMMSE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24.1 (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e142\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParkinsonism\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e120 (87%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e138\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVisual hallucinations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e87 (65%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e134\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eProbable RBD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e55 (47%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e118\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCognitive fluctuations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e50 (52%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e97\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003eMMSE\u0026thinsp;=\u0026thinsp;Mini Mental State Examination. RBD\u0026thinsp;=\u0026thinsp;REM-sleep Behavior Disorder\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eDemographic characteristics and biomarkers of the whole Find-DLB cohort (N\u0026thinsp;=\u0026thinsp;143)\u003c/b\u003e\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows demographic characteristics and presence of core clinical features within the whole cohort. The mean age at final diagnosis was 70.8 years, ranging from 52\u0026ndash;88 years. Approximately 71% were male and the mean years of education was 12.3. The mean MMSE score was 24.1, ranging from 11\u0026ndash;30. Parkinsonism was the most frequent core clinical feature, with 87% of the patients experiencing at least one cardinal feature of parkinsonism. 65% experienced visual hallucinations, 52% had cognitive fluctuations, and 47% had symptoms of probable RBD. In this cohort, cognitive fluctuations was the core symptom least frequently screened for and reported in health records, with data available only for 68% of the cohort.\u003c/p\u003e\u003cp\u003e73% of the whole cohort completed a brain MRI and 74% an EEG exam, while a smaller proportion had an FDG-PET scan (33%). 50% of the patients completed a DaT-scan and 93% of those had a result consistent on reduced dopamine transporter uptake in basal ganglia (coded as positive biomarker result in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). One patient had an inconclusive DaT-scan result according to the clinical report. Amyloid positivity in CSF was more common (20%) than p-tau positivity (8%).\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\u003eAvailable modalities and biomarkers in the whole Find-DLB cohort (n\u0026thinsp;=\u0026thinsp;143)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCount\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePositive\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMRI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e105 (73%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEEG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e106 (74%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeuropsychology\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e96 (67%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFDG-PET\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e54 (38%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDaT-Scan\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e72* (50%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e67 (93%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF Amyloidβ42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e112 (78%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22 (20%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e90 (80%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF P-tau\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e111 (78%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e102 (92%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e*n\u0026thinsp;=\u0026thinsp;1 inconclusive. MRI\u0026thinsp;=\u0026thinsp;Brain Magnetic Resonance Imaging. EEG\u0026thinsp;=\u0026thinsp;Electroencephalography. FDG-PET\u0026thinsp;=\u0026thinsp;Fluorodeoxyglucose Positron Emission Tomography. DaT-Scan\u0026thinsp;=\u0026thinsp;Dopamine Transporter Scan. CSF Amyloidβ42\u0026thinsp;=\u0026thinsp;Cerebrospinal Fluid Amyloid beta 42. CSF P-tau\u0026thinsp;=\u0026thinsp;Cerebrospinal Fluid Phospholyrated Tau.\u003c/p\u003e\u003cp\u003e\u003cb\u003eDemographic characteristics and biomarkers by diagnostic group (DLB, PDD and ND)\u003c/b\u003e\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows the main demographic characteristics and biomarker data for DLB, PDD and ND (the last is for the Non-Dementia group, which is composed of MCI patients). The DLB group was statistically significantly older compared to the ND group. There were no significant group differences in sex distribution or years of education. As expected, ND performed significantly better on MMSE compared to both DLB and PDD. Parkinsonism was the most frequent core clinical feature for all diagnostic groups with 100% of PD patients, almost 90% of DLB patients and 67% of ND patients experiencing parkinsonism. Statistical testing shows that Parkinsonism was significantly more common in PDD compared to ND. Both DLB (69%) and PDD (67%) had a statistically significantly higher frequency of visual hallucinations compared to ND (20%), but there were no significant group differences regarding probable RBD or cognitive fluctuations. In the smaller subsample with available CSF biomarkers and DaT-scan, 27% of DLB participants were amyloid-positive in CSF, which was significantly more frequent than in PDD where only 4% were amyloid-positive. There were no group differences regarding positivity on DaT-scan or P-tau in CSF. DaT-scan was only performed for 51% of all participants within these diagnostic groups. For the remaining participants, DaT-scan status is unknown.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eGroup comparison of demographics and biomarker status of available data\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"8\"\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=\"char\" char=\".\" 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=\"char\" char=\".\" 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=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDLB\u0026thinsp;=\u0026thinsp;88\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ePDD\u0026thinsp;=\u0026thinsp;35\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eND\u0026thinsp;=\u0026thinsp;14\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e72.5 (7.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e87\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e69.4 (7.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e66.6 (6.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003e0.005\u003c/b\u003e a\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex, male\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e62 (71%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e88\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e24 (69%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e11 (79%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.846\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEducation, years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12.0 (3.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e77\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12.4 (3.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e14.0 (4.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.226\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMMSE, total score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23.6 (3.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e87\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e24.0 (3.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e26.9 (2.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003e0.010\u003c/b\u003e a,b\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParkinsonism, presence\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e77 (90%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e34 (100%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e8 (67%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003e0.005\u003c/b\u003e b\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHallucinations, presence\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e59 (69%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e85\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e22 (67%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2 (20%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003e0.010\u003c/b\u003e a,b\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eProbable RBD, presence\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e37 (46%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16 (57%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1 (14%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.134\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFluctuations, presence\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e41 (57%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e72\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (38%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2 (40%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.291\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF Amyloid β42, positive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18 (27%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2 (18%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003e0.025\u003c/b\u003e c\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF P-tau, positive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1 (9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDaT-scan, positive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e46 (96%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16 (94%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4 (80%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.215\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eMean (standard deviation) and count (percentage) are reported as detailed in the table. a) DLB vs ND. b) PDD vs ND. c) DLB vs PDD. DLB\u0026thinsp;=\u0026thinsp;Dementia with Lewy Bodies. PDD\u0026thinsp;=\u0026thinsp;Parkinson\u0026rsquo;s Disease Dementia. ND\u0026thinsp;=\u0026thinsp;Non-Dementia group (composed of MCI patients). MMSE\u0026thinsp;=\u0026thinsp;Mini Mental State Examination. RBD\u0026thinsp;=\u0026thinsp;REM-Sleep Behavior Disorder. Pos DaT-Scan\u0026thinsp;=\u0026thinsp;Positive Dopamine Transporter Scan. CSF Amyloid beta 42\u0026thinsp;=\u0026thinsp;Cerebrospinal Fluid Amyloid beta 42. CSF P-tau\u0026thinsp;=\u0026thinsp;Cerebrospinal Fluid Phospholyrated Tau.\u003c/p\u003e\u003cp\u003e\u003cb\u003eNeuropsychological profile\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe subsample with neuropsychological data included 68 patients. Six patients had completed the neuropsychological assessment\u0026thinsp;\u0026gt;\u0026thinsp;2 years before final diagnosis: one patient with DLB and five patients with PDD. The DLB patient had an MCI-LB diagnosis at previous visits. The five PDD patients had completed the assessment before converting to dementia. Therefore, they were grouped with the PD-MCI patients in the Non-Dementia (ND) group. To keep that group specific for PD, the remaining MCI patients were excluded from further analysis (two with MCI-LB and two MCI without specified cause). The final groups for comparing neuropsychological test performance were as follows (n\u0026thinsp;=\u0026thinsp;63): DLB (n\u0026thinsp;=\u0026thinsp;43), PDD (n\u0026thinsp;=\u0026thinsp;9), and ND (n\u0026thinsp;=\u0026thinsp;11).\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e shows key demographic variables and neuropsychological test performance of DLB, PDD, and ND groups. DLB were older than PDD and ND, significantly so compared to PDD (p\u0026thinsp;=\u0026thinsp;0.037). There were no significant differences in years of education (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003eNeuropsychological test performance was classified into normal or impaired and percentage of impairment was reported (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e) and plotted to build impairment profiles (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Due to the small sample size in the neuropsychological subsample, we first inspected percentage of impairment qualitatively. We observed that DLB generally had higher percentages of impairment compared to both ND and PDD. As expected, ND overall had the lowest proportion of impaired scores. Ordered by frequency of impairment, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows that the most frequently impaired cognitive domains in DLB were visual attention and processing speed. More than 75% of DLB patients were impaired on trail making tasks, both number sequencing and number-letter switching. An even higher proportion of impairment was seen in PDD, where 100% were impaired on number-letter switching task. Out of all cognitive tests, the number-letter switching task showed the highest level of impaired performances across all three groups, including ND (see Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e for full details on percentage of impairment in each diagnostic group).\u003c/p\u003e\u003cp\u003eNext, more than 50% of the DLB group had impaired performance on mental processing speed (Coding), visuospatial constructive tasks (both Block design and RCFT copy), and visual memory (RCFT immediate recall). RCFT copy was impaired in 66% of DLB patients, and free recall was impaired in 69%. In comparison, 50% of PDD patients had impaired performance on these tests.\u003c/p\u003e\u003cp\u003eVerbal learning and delayed recall (RAVLT learning and delayed recall) was impaired in 44% of DLB patients, while ND generally performed within normal range on both learning and delayed recall. PDD had a higher proportion of impaired performance on delayed recall (38%) compared to learning (17%), but it should be noted that the learning trial was missing for two PDD participants.\u003c/p\u003e\u003cp\u003eSemantic memory and general knowledge (Information), auditive short-term memory and working memory (Digit span), abstract verbal thinking (Similarities), and arithmetic ability (Arithmetic) were impaired in less than a third of DLB patients, and logical thinking (Matrix reasoning) was impaired in 35%, meaning that a significant proportion of patients performed within the normal range on these cognitive tests. In comparison, 40% of PDD participants were impaired on Arithmetic, and 50% on Matrix reasoning.\u003c/p\u003e\u003cp\u003e For completeness of information, we followed visual inspection with statistical group comparisons. Despite the reduced statistical power in the smaller subsample with neuropsychological data, we obtained a statistically significant difference between DLB and ND on Block design (p\u0026thinsp;=\u0026thinsp;0.011) and verbal learning on RAVLT (p\u0026thinsp;=\u0026thinsp;0.009), which were both more frequently impaired in DLB. There were no other significant group differences on the other reported neuropsychological tests (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eNeuropsychological test performance\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\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=\"char\" char=\".\" 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=\"char\" char=\".\" 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=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDLB\u0026thinsp;=\u0026thinsp;43\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ePDD\u0026thinsp;=\u0026thinsp;9\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eND\u0026thinsp;=\u0026thinsp;11\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge at NP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e71.4 (7.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e64.8 (6.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e68.7 (7.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEducation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12.4 (3.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11.3 (3.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e14.7 (3.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRAVLT learning\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17 (44%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (17%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRAVLT 30 min\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17 (44%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (38%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1 (10%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRCFT copy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21 (66%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (50%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3 (33%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRCFT recall\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20 (69%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (50%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3 (30%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInformation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (29%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSimilarities\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (27%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (13%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlock design\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24 (59%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (43%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1 (10%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMatrix reasoning\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (35%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (50%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1 (11%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eArithmetic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (32%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (40%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1 (14%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDigit span\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (25%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (17%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCoding\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17 (53%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (43%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1 (13%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTMT numbers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19 (76%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (75%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1 (25%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTMT Let/num\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17 (77%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (100%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2 (40%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eData is presented as count and percentage with impaired performance on each neuropsychological test, stratified by diagnostic group: DLB\u0026thinsp;=\u0026thinsp;Dementia with Lewy Bodies. PDD\u0026thinsp;=\u0026thinsp;Parkinson\u0026rsquo;s Disease Dementia. ND\u0026thinsp;=\u0026thinsp;Non-Dementia group (composed of patients with Parkinson\u0026rsquo;s disease). NP\u0026thinsp;=\u0026thinsp;Neuropsychological assessment. RAVLT\u0026thinsp;=\u0026thinsp;Rey Auditory Verbal Learning Test. RCFT\u0026thinsp;=\u0026thinsp;Rey Complex Figure Test. TMT numbers\u0026thinsp;=\u0026thinsp;Trail Making Test number sequencing. TMT Letter/numbers\u0026thinsp;=\u0026thinsp;Trail Making Test letters and numbers switching.\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eOur main goal was to describe a naturalistic cohort of patients presenting with clinical features of DLB to a specialized cognitive clinic. We describe the diagnostic procedure and report baseline demographic data and neuropsychological profiles. 143 patients were included. 88 patients had a final diagnosis of DLB, while 35 had PDD, 14 MCI, and six patients had other types of dementia. There were no statistically significant differences in frequency of any core clinical features between DLB and PDD. However, amyloid positivity as measured in CSF was significantly more frequent in DLB than in PDD. The Non-Dementia group was heterogenous and included participants with MCI-PD, MCI-LB and MCI without specified cause. Visual hallucinations were less frequent in ND participants compared to both DLB and PDD.\u003c/p\u003e\u003cp\u003e\u003cb\u003eClinical diagnostic challenges\u003c/b\u003e\u003c/p\u003e\u003cp\u003eOut of 143 patients presenting with core clinical features of DLB, 88 fulfilled criteria for probable or possible DLB. A majority of the non-DLB patients had PD-related cognitive impairment, i.e. PDD or PD-MCI. While most of these PD-patients had been diagnosed with PD prior to seeking the cognitive clinic, there may still be challenges in the diagnostic procedure. The average time from PD diagnosis to PDD onset has been reported to be approximately 10 years (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e). An aggressive and faster progression of cognitive decline may raise suspicion of DLB. Some patients or caregivers retrospectively report the onset of cognitive impairment to have been simultaneous or prior to the parkinsonian features, and others receive a diagnosis of dementia closely after the 1-year mark, making it difficult to determine the exact time of dementia onset. As we carefully reviewed cases retrospectively to confirm the final diagnosis, we strictly employed the 1-year rule to properly differentiate DLB from PDD (McKeith et al 2017).\u003c/p\u003e\u003cp\u003eAdditionally, the clinical separation of DLB from AD may be challenging as well. While the proportion of patients receiving a clinical diagnosis of AD was only around 1% in this cohort, some patients had been given a clinical diagnosis of both AD and DLB. When inspecting clinical records in this cohort, we also observed that some patients had received a previous clinical AD diagnosis which was later converted to DLB when core clinical features were unveiled or became more prominent. This phenomenon may reflect the diagnostic difficulties in separating DLB from AD. Previous studies have reported that around 50% of DLB patients show evidence for amyloid-related pathology (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). In our cohort, only 27% of DLB patients were amyloid-positive in CSF. It is possible that this could be explained by DLB patients being misdiagnosed with AD and therefore not included in this cohort. While including patients having two clinical diagnoses of both DLB and AD may complicate specific conclusions for DLB, excluding these patients would limit generalizability to a clinical context. Additionally, if national registers and databases only consider one ICD-10 code to be the primary etiology, the coding of double etiologies may influence the statistics and underestimate the number of DLB patients.\u003c/p\u003e\u003cp\u003e\u003cb\u003eFrequency of core clinical features\u003c/b\u003e\u003c/p\u003e\u003cp\u003eOverall, parkinsonism was the most common core clinical feature across all diagnostic groups in the Find-DLB cohort. 90% of DLB patients had at least one cardinal feature of spontaneous parkinsonism. While we did not stratify for different features of parkinsonism, previous studies have found rigidity and bradykinesia in up to 85% of DLB patients, with lower prevalence of resting tremors (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e). Visual hallucinations were present in almost 70% of DLB patients, in line with previous reports (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e). Probable RBD was the least frequent core feature in our DLB group occurring in 46% of patients, and generally less occurring than in other DLB cohorts which have found RBD to be present in about 76% of neuropathologically confirmed cases (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e). The lower frequency of probable RBD in our cohort may thus be related to the lack of a bed partner to report RDB-related symptoms as well as the lack of polysomnography. Furthermore, the least documented symptom in health records in our cohort was cognitive fluctuations, which has long been considered a difficult symptom to capture (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e). Cognitive fluctuations may be difficult to define and explain to the patient and caregiver. The prospective collection of cases in the Find-DLB cohort has thus included validated questionnaires for probable RBD (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e), and a clinical rating scale for fluctuations (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e). Hence, in the future we will be able to compare the prospective rates with those in the current report based mostly on retrospective cases.\u003c/p\u003e\u003cp\u003e\u003cb\u003eThe \u0026ldquo;cognitive profile\u0026rdquo; of impairment in DLB\u003c/b\u003e\u003c/p\u003e\u003cp\u003eA majority of DLB patients were impaired on visuospatial constructive tasks, visual memory, and processing speed tasks such as digit symbol and trail making tests. This is in line with previous research, which has found the cognitive profile in DLB to show a larger proportion of visual perceptual, attentional, and executive impairment compared to other cognitive domains (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Visual memory impairment in DLB has been shown to be comparable to that of AD (\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e). It is possible that this reflects the visual processing deficit common in DLB influencing the memory encoding process, rather than representing a genuine memory impairment.\u003c/p\u003e\u003cp\u003eInterestingly, 44% of DLB patients had impaired verbal learning and delayed free recall. While the memory deficit in DLB has been hypothesized to be partially related to encoding and retrieval deficits rather than memory storage, previous studies found that a relevant portion of DLB patients may have impaired verbal memory storage and consolidation, even at MCI-LB stages (\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e). A limitation of our Find-DLB cohort is the lack of memory recognition subtasks, which would help clarify whether our memory finding is related to encoding and retrieval or memory storage and consolidation.\u003c/p\u003e\u003cp\u003eWAIS-subtests Digit span and Arithmetic were impaired in less than a third of DLB patients, meaning that a majority performed within normal range on tasks traditionally considered as working memory processes. Previous research has found working memory to be impaired in DLB, and more severely impaired than in AD (\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e). WAIS-subtest Similarities, measuring abstract thinking and considered partly executive in nature, was also preserved in a large proportion of DLB patients in our cohort. It should be noted that the lower proportion of impaired performances on some neuropsychological tests could be influenced by the selection process of the subgroup with neuropsychological assessment in our cohort. In our clinic, patients with severe impairment on cognitive screening may not undergo neuropsychological assessment and thus, would not be included in these analyses.\u003c/p\u003e\u003cp\u003eWhen comparing DLB with PDD, visual inspection suggested similar frequencies of impairment on tests such as complex figure copy and recall, as well as trail making tasks. However, PDD had a lower proportion of impaired patients on several neuropsychological tests. Specifically, impairment in verbal learning in PDD was similar to ND and qualitatively milder than that in patients with DLB. Some previous studies have reported differences in memory impairment between PDD and DLB with a trend towards lower learning and memory retention in DLB, while other studies did not find any significant differences (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). In our study, the qualitative differences between DLB and PDD in cognitive performance are not explained by differences in global cognitive performance as reflected by the MMSE. As expected, ND generally had a smaller proportion of impaired performances on most tests, compared to both DLB and PDD. Despite the limited statistical power in the subsample with neuropsychological data available, we followed visual inspection of percentage of impairment with formal statistical testing for completeness of information. We found that verbal learning from RAVLT and Block design from WAIS were statistically significantly more frequently impaired in DLB than in ND. We did not capture any other statistically significant results, likely because of the small sample size of the PDD and ND groups.\u003c/p\u003e\u003cp\u003eIn summary, cognitive impairment in our DLB patients was primarily characterized by impairment in visuospatial constructive tasks, visual memory, visual attention and processing speed, as well as executive functions as measured by task switching. The profile is in line with previous reports of commonly affected domains in DLB (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Auditory short term- and working memory tasks were less frequently impaired in our DLB group.\u003c/p\u003e\u003cp\u003e\u003cb\u003eLimitations\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThis study has some limitations. Due to the clinical nature of the data, some variables were incomplete and the diagnostic battery for each patient may differ. This may increase the risk of bias, such as within the context of neuropsychological assessment - patients with severe cognitive impairment may be less likely to undergo full neuropsychological evaluation. However, the bias may be less than in research-oriented cohorts that often recruit DLB patients at mild to moderate stages. Furthermore, the small sizes of PDD and ND groups likely limited the possibility to obtain more statistically significant differences in neuropsychological variables. We circumvented this by using normative data and reporting frequencies of impairment across tests as the main analyses, while statistical comparisons were explorative and reported for completeness of information. The selection of norms was made carefully since norms may affect the interpretation of what constitutes an impairment. Further, the chosen norms are applied in the clinic, which improves generalizability to a clinical context. In our study, all norms were age-stratified and, on several tests, norms also took gender and education into account. Age, gender, and education are factors known to influence performance on some cognitive tests. Lastly, we included patients with possible DLB as well as patients with a concurrent clinical diagnosis of DLB and AD, since our aim was to present a realistic and naturalistic clinical cohort. However, whether the frequency of cognitive impairments differs across probable DLB, possible DLB, and DLB cases with a clinical phenotype of mixed AD and DLB should be investigated further.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eThis article describes the Find-DLB cohort, a cohort of patients presenting with clinical features of DLB to our specialized cognitive clinic, in a naturalistic manner. Our study shows that even with access to several diagnostic modalities, diagnosing DLB is challenging within the clinical context. Patients are seeking cognitive evaluation at an earlier stage than before and there is an increasing need to provide more precise diagnostic and prognostic information. The diagnostic process from first visit to primary care physician to a DLB diagnosis is time and resource consuming, both for the health care system and the patient and caregiver. More research should investigate this process and identify the factors susceptible for improvement. The core clinical features are the foundation of the diagnostic process in DLB, and while parkinsonism and visual hallucinations may be more obvious during the clinical assessment, cognitive fluctuations and RBD can be more dubious. Moving forward, the evaluation of these features would benefit from a more systematic data collection using validated clinical rating instruments.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAD\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAlzheimer\u0026rsquo;s Disease\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eADL\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eActivities of Daily Living\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCSF\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eCerebrospinal Fluid\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCT\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eComputer TomographyD-KEFS:Delis\u0026ndash;Kaplan Executive Function System\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eDAT-Scan\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eDopamine Transporter Scan\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eDLB\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eDementia with Lewy Bodies\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eEEG\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eElectroencephalography\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eEOD\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eEarly Onset Dementia\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eFDG\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eFluorodeoxyglucose\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eICD-10\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eInternational Statistical Classification of Diseases and Related Health Problems 10th Revision\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMCI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eMild Cognitive Impairment\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMCI-LB\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eMCI with Lewy bodies\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMMSE\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eMini Mental State Examination\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMoCA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eMontreal Cognitive Assessment\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMRI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eMagnetic Resonance Imaging\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eND\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eNon-Dementia\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePDD\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eParkinsons Disease with dementia\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePD\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eParkinsons Disease\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePD-MCI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eMCI due to PD\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePET\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ePositron Emission Tomography\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ep-tau\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ePhosphorylated tau\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eRAVLT\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eRey Auditory Verbal Learning Test\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eRBD\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eREM-sleep Behavior Disorder\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eRCFT\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eRey Complex Figure Test\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eTMT\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eTrail Making Test\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eWAIS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eWechsler Adult Intelligence Scale\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData has been handled in accordance with GDPR legislation. The study was approved by the Regional Ethics Committee in Stockholm (Dnr: 2013/2169-31) and the following amendments were approved by the Swedish Ethical Review Authority,Uppsala (Dnr: 2019-05978, and 2022-01251-02). This study was carried out in compliance with the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll included patients provided signed written consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDF consults for BioArctic and has received honoraria from Esteve Pharmaceuticals S.A. All other authors declared no competing interests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial Number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that supports the findings of this study are not publicly available due to privacy and are protected by a pseudonymization protocol. Data may be available upon reasonable request from the corresponding author if legal and ethical requirements are met.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDF receives funding from the Swedish Research Council (Vetenskapsr\u0026aring;det, grant 2022-00916), the Center for Innovative Medicine (CIMED, grants 20200505 and FoUI-988826), the regional agreement on medical training and clinical research of Stockholm Region (ALF Medicine, grants FoUI-962240 and FoUI-987534), the Swedish Brain Foundation (Hj\u0026auml;rnfonden FO2023-0261, FO2022-0175, FO2021-0131), the Swedish Alzheimer Foundation (Alzheimerfonden AF-968032, AF-980580, AF-994058, AF-1010553), the Swedish Dementia Foundation (Demensfonden), the Gamla Tj\u0026auml;narinnor Foundation, the Gun och Bertil Stohnes Foundation, the \u0026Aring;ke Wiberg Foundation, StratNeuro, Parkinsonfonden, Funding for Research from Karolinska Institutet, Neurofonden, and the Foundation for Geriatric Diseases at Karolinska Institutet, contributions from private bequests and academic agreements with industry.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSG performed analyses and drafted the manuscript.\u003c/p\u003e\n\u003cp\u003eVJ, SGP, NB,\u0026nbsp;AN\u0026nbsp;and AB contributed to patient recruitment/data acquisition.\u003c/p\u003e\n\u003cp\u003eSG, VJ, and DF contributed to the overall design of the project and AR contributed to statistical design.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAN, TG and DF contributed to the funding for the project.\u003c/p\u003e\n\u003cp\u003eDF provided overall supervision.\u003c/p\u003e\n\u003cp\u003eAll authors contributed to reading and editing of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to extend their gratitude to the patients who participated in this project, as well as the healthcare providers who facilitated the project.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMcKeith IG, Boeve BF, Dickson DW, Halliday G, Taylor JP, Weintraub D et al (2017) Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. Neurology 89(1):88\u0026ndash;100\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHogan DB, Fiest KM, Roberts JI, Maxwell CJ, Dykeman J, Pringsheim T et al (2016) The Prevalence and Incidence of Dementia with Lewy Bodies: a Systematic Review. Can J Neurol Sci 43(Suppl 1):S83\u0026ndash;95\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVann Jones SA, O'Brien JT (2014) The prevalence and incidence of dementia with Lewy bodies: a systematic review of population and clinical studies. Psychol Med 44(4):673\u0026ndash;683\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKane JPM, Surendranathan A, Bentley A, Barker SAH, Taylor JP, Thomas AJ et al (2018) Clinical prevalence of Lewy body dementia. Alzheimers Res Ther 10(1):19\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKantarci K, Lowe VJ, Chen Q, Przybelski SA, Lesnick TG, Schwarz CG et al (2020) β-Amyloid PET and neuropathology in dementia with Lewy bodies. Neurology 94(3):e282\u0026ndash;e91\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRobinson JL, Xie SX, Baer DR, Suh E, Van Deerlin VM, Loh NJ et al (2023) Pathological combinations in neurodegenerative disease are heterogeneous and disease-associated. Brain 146(6):2557\u0026ndash;2569\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIrwin DJ, Grossman M, Weintraub D, Hurtig HI, Duda JE, Xie SX et al (2017) Neuropathological and genetic correlates of survival and dementia onset in synucleinopathies: a retrospective analysis. Lancet Neurol 16(1):55\u0026ndash;65\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMerdes AR, Hansen LA, Jeste DV, Galasko D, Hofstetter CR, Ho GJ et al (2003) Influence of Alzheimer pathology on clinical diagnostic accuracy in dementia with Lewy bodies. Neurology 60(10):1586\u0026ndash;1590\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAldridge GM, Birnschein A, Denburg NL, Narayanan NS (2018) Parkinson's Disease Dementia and Dementia with Lewy Bodies Have Similar Neuropsychological Profiles. Front Neurol 9:123\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFiloteo JV, Salmon DP, Schiehser DM, Kane AE, Hamilton JM, Rilling LM et al (2009) Verbal learning and memory in patients with dementia with Lewy bodies or Parkinson's disease with dementia. J Clin Exp Neuropsychol 31(7):823\u0026ndash;834\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003evan de Beek M, van Steenoven I, van der Zande JJ, Porcelijn I, Barkhof F, Stam CJ et al (2021) Characterization of symptoms and determinants of disease burden in dementia with Lewy bodies: DEvELOP design and baseline results. Alzheimers Res Ther 13(1):53\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRoberts RO, Geda YE, Knopman DS, Cha RH, Pankratz VS, Boeve BF et al (2008) The Mayo Clinic Study of Aging: design and sampling, participation, baseline measures and sample characteristics. Neuroepidemiology 30(1):58\u0026ndash;69\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eElder GJ, Colloby SJ, Lett DJ, O'Brien JT, Anderson KN, Burn DJ et al (2016) Depressive symptoms are associated with daytime sleepiness and subjective sleep quality in dementia with Lewy bodies. Int J Geriatr Psychiatry 31(7):765\u0026ndash;770\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNaharci MI, Kayahan Satis N, Ozsurekci C, Tasci I (2023) Assessment of clinical features and coexisting geriatric syndromes in newly diagnosed dementia with Lewy bodies: a retrospective study in a tertiary geriatrics setting in Turkey. Eur Geriatr Med 14(1):19\u0026ndash;27\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eStatistics Sweden Population density per sq. km, population and land area by region and sex 2023 [Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.statistikdatabasen.scb.se/pxweb/en/ssd/START__BE__BE0101__BE0101C/BefArealTathetKon/\u003c/span\u003e\u003cspan address=\"https://www.statistikdatabasen.scb.se/pxweb/en/ssd/START__BE__BE0101__BE0101C/BefArealTathetKon/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNasreddine ZS, Phillips NA, B\u0026eacute;dirian V, Charbonneau S, Whitehead V, Collin I et al (2005) The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 53(4):695\u0026ndash;699\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFolstein MF, Folstein SE, McHugh PR (1975) Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12(3):189\u0026ndash;198\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eStorey JE, Rowland JT, Basic D, Conforti DA, Dickson HG (2004) The Rowland Universal Dementia Assessment Scale (RUDAS): a multicultural cognitive assessment scale. Int Psychogeriatr 16(1):13\u0026ndash;31\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWinblad B, Palmer K, Kivipelto M, Jelic V, Fratiglioni L, Wahlund LO et al (2004) Mild cognitive impairment\u0026ndash;beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med 256(3):240\u0026ndash;246\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLitvan I, Goldman JG, Tr\u0026ouml;ster AI, Schmand BA, Weintraub D, Petersen RC et al (2012) Diagnostic criteria for mild cognitive impairment in Parkinson's disease: Movement Disorder Society Task Force guidelines. Mov Disord 27(3):349\u0026ndash;356\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMcKeith IG, Ferman TJ, Thomas AJ, Blanc F, Boeve BF, Fujishiro H et al (2020) Research criteria for the diagnosis of prodromal dementia with Lewy bodies. Neurology 94(17):743\u0026ndash;755\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWechsler D (2008) Wechsler Adult Intelligence Scale- Fourth Edition: Technical and interpretive manual, 4th edn. Pearson, San Antonio\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWechsler D (1997) Wechsler Adult Intelligence Scale, 3rd edn. The Psychological Corporation, San Antonio\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRey A (1958) L'examen clinique en psychologie. [The clinical examination in psychology]. Presses Universitaries De France, Oxford, England, pp 222\u0026ndash;p\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRey A (1941) L'examen psychologique dans les cas d'enc\u0026eacute;phalopathie traumatique. (Les problems.). [The psychological examination in cases of traumatic encepholopathy. Probl ] Archives de Psychologie 28:215\u0026ndash;285\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eReitan RM (1955) The relation of the trail making test to organic brain damage. J Consult Psychol 19(5):393\u0026ndash;394\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDelis D (2001) Delis-Kaplan Executive Function System. The Psychological Corporation\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBergman I, Almkvist O (2015) Neuropsychological test norms controlled for physical health: Does it matter? Scand J Psychol 56(2):140\u0026ndash;150\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePetersen RC (2004) Mild cognitive impairment as a diagnostic entity. J Intern Med 256(3):183\u0026ndash;194\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEkman U, Ferreira D, Muehlboeck JS, Wallert J, Rennie A, Eriksdotter M et al (2020) The MemClin project: a prospective multi memory clinics study targeting early stages of cognitive impairment. BMC Geriatr 20(1):93\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRennie A, Ekman U, Shams S, Ryd\u0026eacute;n L, Samuelsson J, Zettergren A et al (2024) Cerebrovascular and Alzheimer\u0026rsquo;s disease biomarkers in dementia with Lewy bodies and other dementias. Brain Commun. ;6(5)\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFerreira D, Jelic V, Cavallin L, Oeksengaard AR, Snaedal J, H\u0026oslash;gh P et al (2016) Electroencephalography Is a Good Complement to Currently Established Dementia Biomarkers. Dement Geriatr Cogn Disord 42(1\u0026ndash;2):80\u0026ndash;92\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFerreira D, Bartr\u0026eacute;s-Faz D, Nygren L, Rundkvist LJ, Molina Y, Machado A et al (2016) Different reserve proxies confer overlapping and unique endurance to cortical thinning in healthy middle-aged adults. Behav Brain Res 311:375\u0026ndash;383\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCorreia R, Nieto A, Ferreira D, Sabucedo M, Barroso J (2015) Fund of Information is More Strongly Associated with Neuropsychological Functioning Than Education in Older Spanish Adults. Arch Clin Neuropsychol 30(4):310\u0026ndash;321\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003evan Steenoven I, Aarsland D, Hurtig H, Chen-Plotkin A, Duda JE, Rick J et al (2014) Conversion between mini-mental state examination, montreal cognitive assessment, and dementia rating scale-2 scores in Parkinson's disease. Mov Disord 29(14):1809\u0026ndash;1815\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAarsland D, Creese B, Politis M, Chaudhuri KR, ffytche DH, Weintraub D, Ballard C (2017) Cognitive decline in Parkinson disease. Nat Reviews Neurol 13(4):217\u0026ndash;231\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePrasad S, Katta MR, Abhishek S, Sridhar R, Valisekka SS, Hameed M et al (2023) Recent advances in Lewy body dementia: A comprehensive review. Dis Mon 69(5):101441\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFerman TJ, Boeve BF, Smith GE, Lin SC, Silber MH, Pedraza O et al (2011) Inclusion of RBD improves the diagnostic classification of dementia with Lewy bodies. Neurology 77(9):875\u0026ndash;882\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBallard CG (2004) Definition and diagnosis of dementia with Lewy bodies. Dement Geriatr Cogn Disord 17(Suppl 1):15\u0026ndash;24\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBoeve BF, Molano JR, Ferman TJ, Lin SC, Bieniek K, Tippmann-Peikert M et al (2013) Validation of the Mayo Sleep Questionnaire to screen for REM sleep behavior disorder in a community-based sample. J Clin Sleep Med 9(5):475\u0026ndash;480\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFerman TJ, Smith GE, Boeve BF, Ivnik RJ, Petersen RC, Knopman D et al (2004) DLB fluctuations: specific features that reliably differentiate DLB from AD and normal aging. Neurology 62(2):181\u0026ndash;187\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eQuerry M, Blanc F, Bousiges O, Philippi N, Cretin B, Demuynck C et al (2023) Memory Outcome in Prodromal and Mild Dementia with Lewy Bodies and Alzheimer's Disease: A Longitudinal Study. J Alzheimers Dis 94(1):147\u0026ndash;162\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOda H, Yamamoto Y, Maeda K (2009) The neuropsychological profile in dementia with Lewy bodies and Alzheimer's disease. Int J Geriatr Psychiatry 24(2):125\u0026ndash;131\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKemp J, Philippi N, Phillipps C, Botzung A, Blanc F (2017) Cognitive profile in prodromal disease (dementia) with Lewy bodies. Geriatr Psychol Neuropsychiatr Vieil 15(4):434\u0026ndash;442\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMacoir J (2022) The Cognitive and Language Profile of Dementia with Lewy Bodies. Am J Alzheimer's Disease Other Dementias\u0026reg; 37:15333175221106901\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Karolinska Institute","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"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},"keywords":"DLB, PDD, Synucleinopathy, Lewy body dementia, Neuropsychology, Biomarkers","lastPublishedDoi":"10.21203/rs.3.rs-7865542/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7865542/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003eDementia with Lewy Bodies (DLB) is a common neurodegenerative disorder, yet difficult to diagnose. Carefully selected research cohorts may not represent the clinical reality. We aimed to characterize a naturalistic cohort of patients with clinical features of DLB, reporting their final diagnosis, clinical features, and cognitive profile.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003ePatients were recruited from a specialized cognitive clinic. Data from patient visits were collected from health records, such as biomarkers, cognitive screening, core clinical features and neuropsychological assessment. We used normative data to assess distribution of impairment in patients with DLB and Parkinsons disease (PD) with and without dementia.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eA total of 143 patients were included in the cohort. Following specialized dementia evaluation, 88 patients fulfilled clinical criteria for DLB, 35 patients for PD with dementia (PDD), 14 had mild cognitive impairment (MCI), and the remaining six patients had other types of dementia. Parkinsonism was the most common core clinical feature (87%), followed by visual hallucinations (65%), cognitive fluctuations (52%) and, lastly, probable REM-sleep behavior disorder (RBD, 47%). A majority of DLB patients had cognitive impairment on visuospatial constructive, attentional and executive tasks, and visual memory.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eThe differential diagnosis of DLB may be difficult within a clinical context because other cognitive disorders frequently present with core features of DLB. The cognitive profile and frequency of core clinical features in the DLB group was generally in line with previous reports. Probable RBD was lower than in other cohorts, which may reflect challenges in collecting this information in a clinical interview.\u003c/p\u003e","manuscriptTitle":"Find-DLB - A naturalistic cohort of patients presenting with clinical features of Dementia with Lewy bodies to a specialized cognitive clinic","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-17 12:45:56","doi":"10.21203/rs.3.rs-7865542/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":"2e3f415a-4477-4272-957c-992992e14145","owner":[],"postedDate":"October 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":56328268,"name":"Geriatrics \u0026 Gerontology"},{"id":56328269,"name":"Neurology"}],"tags":[],"updatedAt":"2025-10-17T12:45:56+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-17 12:45:56","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7865542","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7865542","identity":"rs-7865542","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}