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Objective: This study assessed the relationship between speech and language impairment and outcome in a multicenter cohort of isolated/idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD)., Methods: Patients with iRBD from 7 centers speaking Czech, English, German, French, and Italian languages underwent a detailed speech assessment at baseline. Story-tale narratives were transcribed and linguistically annotated using fully automated methods based on automatic speech recognition and natural language processing algorithms, leading to the 3 distinctive linguistic and 2 acoustic patterns of language deterioration and associated composite indexes of their overall severity. Patients were then prospectively followed and received assessments for parkinsonism or dementia during follow-up. The Cox proportional hazard was performed to evaluate the predictive value of language patterns for phenoconversion over a follow-up period of 5 years., Results: Of 180 patients free of parkinsonism or dementia, 156 provided follow-up information. After a mean follow-up of 2.7 years, 42 (26.9%) patients developed neurodegenerative disease. Patients with higher severity of linguistic abnormalities (hazard ratio [HR = 2.35]) and acoustic abnormalities (HR = 1.92) were more likely to develop a defined neurodegenerative disease, with converters having lower content richness (HR = 1.74), slower articulation rate (HR = 1.58), and prolonged pauses (HR = 1.46). Dementia-first (n = 16) and parkinsonism-first with mild cognitive impairment (n = 9) converters had higher severity of linguistic abnormalities than parkinsonism-first with normal cognition converters (n = 17)., Interpretation: Automated language analysis might provide a predictor of phenoconversion from iRBD into synucleinopathy subtypes with cognitive impairment, and thus can be used to stratify patients for neuroprotective trials. ANN NEUROL 2024;95:530-543., (© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background and Objectives: Patients with isolated/idiopathic REM sleep behavior disorder (iRBD) are at high risk for developing mild cognitive impairment (MCI) and dementia with Lewy bodies (DLB). However, there is a lack of scientific knowledge regarding the accuracy of cognitive screening tools to identify these conditions in iRBD. This study aimed to determine in iRBD the psychometrics of 2 screening tests to discriminate patients with MCI and those at risk of DLB., Methods: We retrospectively selected and followed 64 patients with polysomnography-confirmed iRBD seen in sleep clinic between 2006 and 2021, 32 with MCI (mean age 68.44 years, 72% men), 32 without MCI (67.78 years, 66% men), and 32 controls (69.84 years, 47% men). Participants underwent a neurologic evaluation and neuropsychological assessment for MCI diagnosis. They also completed the Montreal Cognitive Assessment (MoCA) and Clock Drawing Test (CDT). Fifty-three patients were followed (mean of 5.10 ± 2.64 years); 6 developed DLB, and 16 developed Parkinson disease. An independent cohort of 10 patients with iRBD who later developed DLB was also recruited and followed. Receiver operating characteristic curves with area under the curve (AUC) were performed assessing the discriminant value of the MoCA and CDT., Results: The cut-off values that best differentiated patients who developed DLB from controls were on the MoCA total score (≤25/30 with 100% [95% CI 61%-100%] sensitivity and 78% [61%-89%] specificity, AUC = 0.888) and delayed recall (≤3/5 with 83% [44%-97%] sensitivity and 78% [61%-89%] specificity, AUC = 0.875). Both values yielded a sensitivity of 90% (60%-98%) to detect patients at risk of DLB in the independent cohort. Cutoffs that best discriminated patients with MCI from controls were: ≤25/30 (MoCA total score) with 72% [55%-84%] sensitivity, 78% [61%-89%] specificity, AUC = 0.803 and ≤2/5 (MoCA delayed recall) with 63% [45%-77%] sensitivity, 94% [80%-98%] specificity, AUC = 0.843. No acceptable optimal values were found for the CDT., Discussion: In iRBD, the MoCA demonstrates adequate psychometric properties to identify patients most at risk of developing DLB and to screen for MCI, whereas the CDT does not., Classification of Evidence: This study provides Class II evidence that the MoCA, but not the CDT, is useful in screening patients with iRBD for the risk of developing DLB.

Introduction: Isolated/idiopathic rapid eye movement sleep behavior disorder (iRBD) is a powerful early predictor of dementia with Lewy bodies (DLB) and Parkinson's disease (PD). This provides an opportunity to directly observe the evolution of prodromal DLB and to identify which cognitive variables are the strongest predictors of evolving dementia., Methods: IRBD participants (n = 754) from 10 centers of the International RBD Study Group underwent annual neuropsychological assessment. Competing risk regression analysis determined optimal predictors of dementia. Linear mixed-effect models determined the annual progression of neuropsychological testing., Results: Reduced attention and executive function, particularly performance on the Trail Making Test Part B, were the strongest identifiers of early DLB. In phenoconverters, the onset of cognitive decline began up to 10 years prior to phenoconversion. Changes in verbal memory best differentiated between DLB and PD subtypes., Discussion: In iRBD, attention and executive dysfunction strongly predict dementia and begin declining several years prior to phenoconversion., Highlights: Cognitive decline in iRBD begins up to 10 years prior to phenoconversion. Attention and executive dysfunction are the strongest predictors of dementia in iRBD. Decline in episodic memory best distinguished dementia-first from parkinsonism-first phenoconversion., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Rapid-eye-movement sleep behavior disorder (RBD) is a major risk factor for Parkinson's disease and dementia with Lewy bodies. More than a third of RBD patients have mild cognitive impairment (MCI), but their specific structural brain alterations remain poorly understood., Objective: This study aimed to investigate the local deformation and volume of gray and white matter tissue underlying MCI in RBD., Methods: Fifty-two idiopathic RBD patients, including 17 with MCI (33%), underwent polysomnography, neuropsychological, neurological, and magnetic resonance imaging assessments. MCI diagnosis was based on a subjective complaint, cognitive impairment on the neuropsychological battery, and preserved daily functioning. Forty-one controls were also included. Deformation-based morphometry (DBM), voxel-based morphometry (VBM), and regional volume analyses of the corpus callosum and cholinergic basal forebrain were performed. Multiple regression models were also computed using anatomical, cognitive (composite z scores), and motor parameters., Results: Globally, patients with MCI displayed a widespread pattern of local deformation and volume atrophy in the cortical (bilateral insula, cingulate cortex, precuneus, frontal, temporal and occipital regions, right angular gyrus, and mid-posterior segment of the corpus callosum) and subcortical (brainstem, corona radiata, basal ganglia, thalamus, amygdala, and right hippocampus) regions compared to patients without MCI (DBM) or controls (DBM and VBM). Moreover, brain deformation (DBM) in patients were associated with lower performance in attention and executive functions, visuospatial abilities, and higher motor symptoms severity., Conclusion: The present study identified novel brain structural alterations in RBD patients with MCI which correlated with poorer cognitive performance. These results are consistent with those reported in patients with synucleinopathies-related cognitive impairment.

Introduction : The neurocognitive outcomes of sustaining a mild traumatic brain injury (mTBI) during late adulthood are vastly understudied. In young, asymptomatic adults, mTBI-related synaptic plasticity alterations have been associated with persistent implicit motor sequence learning impairments outlasting the usual cognitive recovery period. The current study examined whether uncomplicated mTBI sustained during late adulthood could exert persistent deleterious consequences on implicit motor sequence learning. Method : Thirty participants (aged 50-70 years) who experienced an uncomplicated mTBI within 3 to 24 months of testing, and 40 age-, sex- and education-equivalent healthy controls performed an implicit serial reaction time task (SRT task). The SRT task consisted of 10 blocks of a repeating sequence embedded among 4 random blocks. Participants also completed a battery of standardized neuropsychological tests of attention, memory and executive functioning. Results : While both mTBI participants and controls showed significant implicit motor sequence learning effects, the mTBI group achieved a lower level of competence at performing the SRT task as evidenced by smaller gains in reaction times across the 10 training blocks of the repeating sequence. The time elapsed since the injury was unrelated to implicit motor learning effects. There was no evidence of a persistent effect of mTBI on any neuropsychological domain compared to controls. Conclusions : Findings from this study suggest that a single mTBI sustained during older age may have persistent repercussions on training-dependent motor sequence learning capacity outlasting the recovery of mTBI symptoms and gold-standard neuropsychological tests performance.

Epidemiological studies have revealed that behavioral and psychological (or non-cognitive) symptoms are risk factors for cognitive decline in older adults. This study aimed to systematically review the literature and determine which behavioral and psychological symptoms are most predictive of future cognitive decline among individuals with no pre-existing cognitive impairments. The selected studies included middle-aged or older adults without cognitive impairments. The predictors were assessed using behavioral and psychological questionnaires, or diagnostic interviews, to identify non-cognitive symptoms or psychiatric clinical conditions. The follow-up period was at least one year, and the design of the selected studies was either retrospective or prospective. This study compared individuals with and without non-cognitive manifestations and resulted in one of three outcomes: (a) a score change on a cognitive measure, (b) a diagnosis of mild cognitive impairment, or (c) a diagnosis of Alzheimer's disease or dementia. Four online databases were searched for eligible studies from the database inception to January 17, 2017: MEDLINE (PubMed), Embase (OVID), PsycINFO, and Web of Science. Pooled effect sizes were estimated using a random-effect model. Higgins I 2 , the Q statistic, and tau-squared were used to quantify the observed heterogeneity between the studies. Results indicate that depression and sleep duration (long and short) were the most consistent associations between behavioral or psychological symptoms and cognitive decline. This meta-analysis supports the need to assess behavioral and psychological symptoms in cognitively intact older adults to identify those who are at risk for cognitive decline.

Objective: The concepts of mild cognitive impairment (MCI) and subjective cognitive decline (SCD) have been proposed to identify individuals in the early stages of Alzheimer's disease (AD), or other neurodegenerative diseases. One approach to validate these concepts is to investigate the relationship between pathological brain markers and cognition in those individuals., Method: We included 126 participants from the Consortium for the Early Identification of Alzheimer's disease-Quebec (CIMA-Q) cohort (67 SCD, 29 MCI, and 30 cognitively healthy controls [CH]). All participants underwent a complete cognitive assessment and structural magnetic resonance imaging. Group comparisons were done using cognitive data, and then correlated with hippocampal volumes and white matter hyperintensities (WMHs)., Results: Significant differences were found between participants with MCI and CH on episodic and executive tasks, but no differences were found when comparing SCD and CH. Scores on episodic memory tests correlated with hippocampal volumes in both MCI and SCD, whereas performance on executive tests correlated with WMH in all of our groups., Discussion: As expected, the SCD group was shown to be cognitively healthy on tasks where MCI participants showed impairment. However, SCD's hippocampal volume related to episodic memory performances, and WMH to executive functions. Thus, SCD represents a valid research concept and should be used, alongside MCI, to better understand the preclinical/prodromal phase of AD., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Background: Though visual illusions and hallucinations are common in dementia with Lewy bodies (DLB) and Parkinson's disease (PD), they are not typically observed clinically in prodromal stages, including isolated REM sleep behavior disorder (iRBD). False-noise errors on the pareidolia test (seeing faces when none are present) may be an effective measure of susceptibility to future hallucinations in iRBD., Methods: One hundred patients with iRBD underwent the 20-image pareidolia test. Clinical markers were assessed and a neuropsychological battery was administered. An exploratory analysis on the impact of pareidolic errors on phenoconversion was also performed., Results: In our cohort, 17 patients (17%) made false-noise pareidolic errors. These patients had significantly lower total Montreal Cognitive Assesment (MoCA) scores (26.7 ± 2.3 vs. 24.4 ± 2.6, B = -1.88, 95% CI: [-3.17, -0.59]), with lower subcomponent MoCA scores on memory and visuospatial-executive sections. Pareidolic errors were also associated with lower visuospatial, attention/executive, and memory scores on the neuropsychological tests. Furthermore, after 1.6 years follow-up, 3/16 (19%) patients making pareidolic errors had phenoconverted at time of publication compared to 6/71 (8%) patients who did not make errors., Conclusion: Pareidolic errors in patients with iRBD are associated with poorer overall cognition and may indicate higher risk of DLB., Competing Interests: Declaration of competing interest The authors have no financial disclosures in relationship to this manuscript., (Copyright © 2020. Published by Elsevier Ltd.)

Background: More than 75% of Parkinson's disease (PD) patients will develop dementia. Previous studies on the cognitive predictors of dementia in PD had some methodological limitations and the cognitive tests identified as good predictors vary greatly., Objective: This prospective cohort study aims to identify the optimal cognitive predictors of dementia in PD using complementary statistical methods., Methods: Eighty PD patients without dementia underwent polysomnographic recording, a neurological examination, and a complete neuropsychological assessment at baseline. They were then followed for a mean of 4.3 years. Baseline group comparisons and survival analyses were used to identify optimal cognitive predictors. Moreover, patients who developed dementia were pair-matched at baseline according to age, sex, and education to healthy controls (2 : 1), and receiver operating characteristic curves were calculated for cognitive tests., Results: At follow-up, 23 patients (29%) developed dementia. PD patients who developed dementia had poorer baseline performance and a higher proportion of clinically impaired performance on several cognitive tests. Impaired baseline performance on the Block Design subtest was the best independent predictor of dementia (HR = 8). Moreover, the Trail Making Test part B (time) and Verbal Fluency (semantic) had the best psychometric properties (area under the curve >0.90) for identifying PD patients at risk of dementia., Conclusion: The present study identified three cognitive tests as the most accurate to detect individuals with PD at high risk of developing dementia.

Background: Genetic, biologic and clinical data suggest that Parkinson's disease (PD) is an umbrella for multiple disorders with clinical and pathological overlap, yet with different underlying mechanisms. To better understand these and to move towards neuroprotective treatment, we have established the Quebec Parkinson Network (QPN), an open-access patient registry, and data and bio-samples repository., Objective: To present the QPN and to perform preliminary analysis of the QPN data., Methods: A total of 1,070 consecutively recruited PD patients were included in the analysis. Demographic and clinical data were analyzed, including comparisons between males and females, PD patients with and without RBD, and stratified analyses comparing early and late-onset PD and different age groups., Results: QPN patients exhibit a male:female ratio of 1.8:1, an average age-at-onset of 58.6 years, an age-at-diagnosis of 60.4 years, and average disease duration of 8.9 years. REM-sleep behavior disorder (RBD) was more common among men, and RBD was associated with other motor and non-motor symptoms including dyskinesia, fluctuations, postural hypotension and hallucinations. Older patients had significantly higher rates of constipation and cognitive impairment, and longer disease duration was associated with higher rates of dyskinesia, fluctuations, freezing of gait, falls, hallucinations and cognitive impairment. Since QPN's creation, over 60 studies and 30 publications have included patients and data from the QPN., Conclusions: The QPN cohort displays typical PD demographics and clinical features. These data are open-access upon application (http://rpq-qpn.ca/en/), and will soon include genetic, imaging and bio-samples. We encourage clinicians and researchers to perform studies using these resources.

Objective: The ability to execute delayed intentions, known as prospective memory (PM), is crucial to everyday living. PM failures are reported in mild cognitive impairment (MCI) and Parkinson's disease, however, no study to date has investigated PM functioning in individuals at high risk of developing these conditions, precisely those diagnosed with idiopathic REM sleep behavior disorder (iRBD). We aimed to assess PM in iRBD according to patients' cognitive status and to determine the underlying nature of their difficulties., Method: Fifty-eight participants, including 20 healthy controls (HC) and 38 polysomnographic-confirmed iRBD patients with (iRBD-MCI = 13) or without (iRBD-nMCI = 25) MCI participated in this study. Following a neuropsychological assessment, PM was evaluated using a self-administered questionnaire (PRMQ), a simple clinical measure (envelope test), and a laboratory cue salience task., Results: No significant group differences were noted on the PRMQ and envelope test. On the PM laboratory task, non-parametric analyses revealed better detection accuracy in HC than both iRBD groups for all high and low salient cues. While iRBD-nMCI and iRBD-MCI patients performed similarly on the high salient condition, the latter showed significant difficulty in detecting low salient cues. Multiple regression analyses revealed executive dysfunction as the best predictor to significantly account for differences in the low salient condition in iRBD., Conclusion: PM difficulties in iRBD are most important in patients with MCI (vs without MCI) and may be attributed to a gradual alteration in executive mechanisms. PM impairment could act as a promising indicator of early cognitive dysfunction in iRBD.

Study Objectives: Recent studies show that obstructive sleep apnea (OSA) is a possible contributor to abnormal cognitive decline in older adults. These new observations create the need to identify older adults with OSA who are at risk of the developing dementia if not treated. This study's goal was to verify whether self-reported cognitive complaints could become a useful tool to screen for objective cognitive deficits in late middle-aged and older adults with OSA., Methods: Fifty-seven participants with OSA with an apnea-hypopnea index (AHI) ≥ 15 events/h (3% or arousal) and aged between 55 and 85 years were compared to 54 participants in a mild/non-OSA group on their ability to evaluate their objective cognitive functioning. They underwent overnight polysomnography followed by a comprehensive neuropsychological assessment. We recruited a similar proportion of participants with mild cognitive impairment (MCI) in both groups (OSA: 36.8%; mild/non-OSA: 35.2%). They filled out questionnaires assessing mood, sleep, and cognition. Group (OSA versus mild/non-OSA) × cognitive status (MCI versus non-MCI) analyses of variance were performed on cognitive complaint questionnaires., Results: We found that among participants without objective cognitive deficits, participants in the OSA group reported more cognitive complaints compared to those in the mild/non-OSA group. Among participants with objective cognitive deficits, those in the OSA group reported less cognitive complaints compared to those in the mild/non-OSA group., Conclusions: Participants with OSA and MCI were less aware of their deficits compared to those in the mild/non-OSA group, possibly reflecting a distinctive OSA-associated cognitive impairment. Our results underscore the importance of referring patients with OSA for a comprehensive neuropsychological assessment when an abnormal cognitive decline is suspected., (© 2019 American Academy of Sleep Medicine.)

Obstructive sleep apnoea increases the risk for mild cognitive impairment and dementia. The present study aimed to characterise the ability of two cognitive screening tests, the Mini-Mental State Examination and the Montreal Cognitive Assessment, to detect mild cognitive impairment in adults aged 55-85 years with and without obstructive sleep apnoea.We included 42 subjects with mild and 67 subjects with moderate-to-severe obstructive sleep apnoea. We compared them to 22 control subjects. Mild cognitive impairment was diagnosed by a comprehensive neuropsychological assessment. We used receiver operating characteristic curves to assess the ability of the two screening tests to detect mild cognitive impairment.The two screening tests showed similar discriminative ability in control subjects. However, among the mild and the moderate-to-severe obstructive sleep apnoea groups, the Mini-Mental State Examination was not able to correctly identify subjects with mild cognitive impairment. The Montreal Cognitive Assessment's discriminant ability was acceptable in both sleep apnoea groups and was comparable to what was observed in controls.The Mini-Mental State Examination should not be used to screen for cognitive impairment in patients with obstructive sleep apnoea. The Montreal Cognitive Assessment could be used in clinical settings. However, clinicians should refer patients for neuropsychological assessment when neurodegenerative processes are suspected., Competing Interests: Conflict of interest: K. Gagnon has nothing to disclose. Conflict of interest: A-A. Baril reports government agency scholarships from Canadian Institutes of Health Research and Fonds de la Recherche du Québec-Santé, during the conduct of the study. Conflict of interest: J. Montplaisir reports personal fees for advisory board work from Novartis, Merck Pharmaceutical and Otsuka Pharmaceutical, outside the submitted work. Conflict of interest: J. Carrier reports grants to the Canadian Sleep and Circadian Network from RANA, Respironics and Merck, outside the submitted work. Conflict of interest: S. Chami has nothing to disclose. Conflict of interest: S. Gauthier reports government agency grants from Canadian Institutes of Health Research, during the conduct of the study; and grants from CQDM network, government agency grants from Pfizer-Fond de Recherche du Québec-Santé and Canadian Institutes of Health Research, personal fees for clinical trial support and scientific advisory work from Lilly, Roche and TauRx, personal fees for clinical trial support from Lundbeck, personal fees for scientific advisory work from AbbVie, ADvantage, Alzheon, Axovant, Boehringer Ingelheim, Firalis, Heptares, IntelGen, Klagene, Novartis, Otsuka, Servier, Sanofi, Schwabe and Takeda, and is a member of data and safety monitoring boards for the Alzheimer's Disease Cooperative Study and Alzheimer's Disease Therapeutic Research Institute, outside the submitted work. Conflict of interest: C. Lafond has nothing to disclose. Conflict of interest: J-F. Gagnon reports grants from W. Garfield Weston Foundation, Canadian Institutes of Health Research, Canada Research Chair and Fonds de Recherche du Québec-Santé, during the conduct of the study. Conflict of interest: N. Gosselin reports government agency grants from Canadian Institutes of Health Research, and government agency grants and salary awards from Fonds de Recherche du Québec-Santé, during the conduct of the study., (Copyright ©ERS 2018.)

Introduction: Studies estimate that >80% of patients with idiopathic REM sleep behavior disorder (iRBD) eventually develop parkinsonism or dementia. However, a small group remains disease-free for long periods, raising the question of whether they truly have prodromal disease., Methods: We selected subjects with iRBD who were diagnosed at least 10 years previously, and were still disease free (longstanding iRBD) (n = 11). We compared them to 'early converters' (n = 27) defined as those who phenoconverted to parkinsonism or dementia within 4 years after diagnosis, and to age- and sex-matched healthy controls (n = 68). We compared the frequency and progression of numerous markers of prodromal synucleinopathy between groups, and assessed likelihood of meeting prodromal Parkinson's disease criteria., Results: After at least 10 years follow-up, almost all longstanding iRBD subjects showed multiple features of neurodegeneration, and 9/11 met criteria for prodromal PD. Evolution of markers was slower than early-converters, with an annual increase in prodromal PD probability of 3.9 ± 3.2% in longstanding iRBD compared to 12.4 ± 7.8% for early-convertors (p-value = 0.002). However, subjects with longstanding iRBD at their last visit had similar prodromal measures as the baseline evaluation of the early-convertors, with similarly-abnormal UPDRS scores, quantitative motor tests, cognition and autonomic symptoms and signs., Conclusion: Although phenoconversion rates can differ dramatically between patients, almost all individuals with iRBD in our cohort appear to have underlying neurodegeneration., (Copyright © 2018. Published by Elsevier Ltd.)

Objective: We describe the progression of cognitive decline and identify the predictive values of cognitive tests in three groups of REM sleep behavior disorder (RBD) patients classified at their last follow-up as having Parkinson's disease (PD), dementia with Lewy bodies (DLB), or still-idiopathic., Methods: Patients (n = 109) underwent polysomnographic, neurological, and neuropsychological assessments. We used linear mixed-model analyses to compare the progression of cognitive test performance between the three groups over a 3-year prodromal period, and performed linear regressions for a 6-year prodromal period. We compared the proportions of patients with clinically impaired performance (z scores < -1.5). DLB patients were pair-matched according to age, sex, and education to healthy controls (2:1 ratio), and receiver operating characteristic curves were performed to identify the psychometric properties of cognitive tests to predict dementia., Results: At follow-up, 38 patients (35%) developed a neurodegenerative disorder: 20 had PD and 18 DLB. Cognitive performance changes over time were strongly associated with later development of dementia. Clear deficits in attention and executive functions were observed 6 years before diagnosis. Verbal episodic learning and memory deficits started later, deviating from normal approximately 5 to 6 years and becoming clinically impaired at 1 to 2 years before diagnosis. Visuospatial abilities progressed variably, with inconsistent prodromal latencies. The Trail Making Test (part B), Verbal Fluency (semantic), and Rey Auditory-Verbal Learning Test (total, immediate, and delayed recalls) were the best predictors for dementia (area under the curve = 0.90-0.97)., Interpretation: Prodromal DLB is detectible up to 6 years before onset. For clinical utility, the Trail Making Test (part B) best detects early prodromal dementia stages, whereas Verbal Fluency (semantic) and verbal episodic learning tests are best for monitoring changes over time. Ann Neurol 2018;83:1016-1026., (© 2018 American Neurological Association.)

Objective: The Clock Drawing Test (CDT) is frequently used to screen for cognitive impairment, however, normative data for Rouleau et al.'s scoring system are scarce. The present study aims to provide norms for Rouleau et al.'s scoring system that are tailored to Quebec French-speaking mid- and older aged healthy adults., Methods: Six researchers from various research centers across the Province of Quebec (Canada) sent anonymous data for 593 (391 women) healthy community-dwelling volunteers (age range: 43-93 years; education range: 5-23 years) who completed the CDT 'drawing on command' version. This command version (setting the clock hands to 11:10, without a pre-drawn circle) was administrated as part of a more extensive neuropsychological assessment, or along with cognitive screening instruments. Each drawn clock was scored according to the quantitative criteria set by Rouleau et al.'s scoring system., Results: CDT scores were significantly correlated with age (r(592) = -.132, p = .001) and years of education (r(592) = .116, p = .005), but not with sex (r(592) = .065, p = .112). Since data were skewed towards higher test scores, the percentiles method was used for analysis. Percentile ranks stratified by age and education are presented., Conclusion: These normative data for Rouleau et al.'s scoring system will contribute towards adequately screening for cognitive decline in Quebec French-speaking healthy adults, by also taking into account individual characteristics such as age and education.

Study Objectives: REM sleep behavior disorder (RBD) is a parasomnia affecting 33% to 46% of patients with Parkinson's disease (PD). The existence of a unique and specific impaired cognitive profile in PD patients with RBD is still controversial. We extensively assessed cognitive functions to identify whether RBD is associated with more severe cognitive deficits in nondemented patients with PD., Methods: One hundred sixty-two participants, including 53 PD patients with RBD, 40 PD patients without RBD, and 69 healthy subjects, underwent polysomnography, a neurological assessment and an extensive neuropsychological exam to assess attention, executive functions, episodic learning and memory, visuospatial abilities, and language., Results: PD patients with RBD had poorer and clinically impaired performance in several cognitive tests compared to PD patients without RBD and healthy subjects. These two latter groups were similar on all cognitive measures. Mild cognitive impairment (MCI) diagnosis frequency was almost threefold higher in PD patients with RBD compared to PD patients without RBD (66% vs. 23%, p < .001). Moreover, subjective cognitive decline was reported in 89% of PD patients with RBD compared to 58% of PD patients without RBD (p = .024)., Conclusions: RBD in PD is associated with a more impaired cognitive profile and higher MCI diagnosis frequency, suggesting more severe and widespread neurodegeneration. This patient subgroup and their caregivers should receive targeted medical attention to better detect and monitor impairment and to enable the development of management interventions for cognitive decline and its consequences., (© Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Introduction: Prodromal markers of Alzheimer's disease (AD) have been derived from wakefulness. However, brain perfusion during rapid-eye movement (REM) sleep could be a sensitive marker of amnestic mild cognitive impairment (aMCI), as activation of REM sleep relies more on the cholinergic system., Methods: Eight subjects with aMCI, and 16 controls, underwent two single-photon emission computed tomography (SPECT) scans with tracer injected during REM sleep then wakefulness., Results: Perfusion in the anterior cingulate cortex was significantly decreased in aMCI cases compared to controls for both conditions. That defect was much larger and more severe in REM sleep (1795 voxels) compared to wakefulness (398 voxels), and extended to the middle cingulate cortex and the olfactory cortex. Hypoperfusion in the anterior cingulate cortex during REM sleep allowed better classification than hypoperfusion found in wakefulness (93.8 vs 81.3%)., Conclusion: REM sleep imaging is a valuable tool with which to identify individuals at risk of developing AD., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: Prospective memory (PM) is a cognitive function defined as the ability to perform an intention at an appropriate moment in the future. In the aging population, PM is essential for maintaining independent daily living. Introduced as a simple and quick way to assess PM in clinical settings, the envelope task has to date received very limited empirical and practical interest., Methods: The present study investigated the task's clinical utility in detecting PM impairment in a sample composed of 49 healthy older adults (OA), 41 patients with Alzheimer's disease, and 64 individuals with amnestic and nonamnestic mild cognitive impairment (MCI) of heterogeneous etiology: 17 of idiopathic nature, 20 presenting an idiopathic rapid-eye movement sleep behaviour disorder, and 27 patients diagnosed with idiopathic Parkinson's disease., Results: The envelope task was highly sensitive and specific in discriminating Alzheimer's disease patients from OA. Although it was specific in distinguishing MCI individuals from OA, its sensitivity was modest, especially in patients presenting a nonamnestic MCI subtype., Conclusions: Given its high specificity and simple low-cost administration procedure, the envelope task is a promising instrument for clinicians who seek to rapidly assess PM impairment in their daily practice.

In a prospective study, we recently discovered 8 clinical predictors of dementia in Parkinson's disease. Here, we validate these dementia predictors using two additional prospective cohorts (n = 134). After a 3.6-year follow-up, 35/134 developed dementia (7.2% per year). When confirming individual variables, 5/8 were significantly associated with dementia in the validation cohort. These included age, male sex, baseline RBD, orthostatic hypotension, and MCI. Bilateral onset, hallucinations and falls/freezing did not significantly predict dementia; however, point estimates of OR were all >1. In all cohorts, the strongest determinant for dementia development was the co-existence of RBD, MCI and orthostatic hypotension at baseline.

The basal forebrain cholinergic system, which is impaired in early Alzheimer's disease, is more crucial for the activation of rapid-eye-movement (REM) sleep electroencephalogram (EEG) than it is for wakefulness. Quantitative EEG from REM sleep might thus provide an earlier and more accurate marker of the development of Alzheimer's disease in subjects with mild cognitive impairment (MCI) subjects than that from wakefulness. To assess the superiority of the REM sleep EEG as a screening tool for preclinical Alzheimer's disease, 22 subjects with amnestic MCI (a-MCI; 63.9±7.7 years), 10 subjects with nonamnestic MCI (na-MCI; 64.1±4.5 years) and 32 controls (63.7±6.6 years) participated in the study. Spectral analyses of the waking EEG and REM sleep EEG were performed and the [(delta+theta)/(alpha+beta)] ratio was used to assess between-group differences in EEG slowing. The a-MCI subgroup showed EEG slowing in frontal lateral regions compared to both na-MCI and control groups. This EEG slowing was present in wakefulness (compared to controls) but was much more prominent in REM sleep. Moreover, the comparison between amnestic and nonamnestic subjects was found significant only for the REM sleep EEG. There was no difference in EEG power ratio between na-MCI and controls for any of the 7 cortical regions studied. These findings demonstrate the superiority of the REM sleep EEG in the discrimination between a-MCI and both na-MCI and control subjects., (© EEG and Clinical Neuroscience Society (ECNS) 2015.)

Importance: There is increasing evidence that Parkinson disease (PD) is heterogeneous in its clinical presentation and prognosis. Defining subtypes of PD is needed to better understand underlying mechanisms, predict disease course, and eventually design more efficient personalized management strategies., Objectives: To identify clinical subtypes of PD, compare the prognosis and progression rate between PD phenotypes, and compare the ability to predict prognosis in our subtypes and those from previously published clustering solutions., Design, Setting, and Participants: Prospective cohort study. The cohorts were from 2 movement disorders clinics in Montreal, Quebec, Canada (patients were enrolled during the period from 2005 to 2013). A total of 113 patients with idiopathic PD were enrolled. A comprehensive spectrum of motor and nonmotor features (motor severity, motor complications, motor subtypes, quantitative motor tests, autonomic and psychiatric manifestations, olfaction, color vision, sleep parameters, and neurocognitive testing) were assessed at baseline. After a mean follow-up time of 4.5 years, 76 patients were reassessed. In addition to reanalysis of baseline variables, a global composite outcome was created by merging standardized scores for motor symptoms, motor signs, cognitive function, and other nonmotor manifestations., Main Outcomes and Measures: Changes in the quintiles of the global composite outcome and its components were compared between different subtypes., Results: The best cluster solution found was based on orthostatic hypotension, mild cognitive impairment, rapid eye movement sleep behavior disorder (RBD), depression, anxiety, and Unified Parkinson's Disease Rating Scale Part II and Part III scores at baseline. Three subtypes were defined as mainly motor/slow progression, diffuse/malignant, and intermediate. Despite similar age and disease duration, patients with the diffuse/malignant phenotype were more likely to have mild cognitive impairment, orthostatic hypotension, and RBD at baseline, and at prospective follow-up, they showed a more rapid progression in cognition (odds ratio [OR], 8.7 [95% CI, 4.0-18.7]; P < .001), other nonmotor symptoms (OR, 10.0 [95% CI, 4.3-23.2]; P < .001), motor signs (OR, 4.1 [95% CI, 1.8-9.1]; P = .001), motor symptoms (OR, 2.9 [95% CI, 1.3-6.2]; P < .01), and the global composite outcome (OR, 8.0 [95% CI, 3.7-17.7]; P < .001)., Conclusions and Relevance: It is recommended to screen patients with PD for mild cognitive impairment, orthostatic hypotension, and RBD even at baseline visits. These nonmotor features identify a diffuse/malignant subgroup of patients with PD for whom the most rapid progression rate could be expected.

Background: Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is a well-documented risk factor for synucleinopathies such as Parkinson disease (PD) and dementia with Lewy bodies (DLB). Moreover, approximately 50% of iRBD patients have mild cognitive impairment (MCI). The purpose of our study was to investigate waking electroencephalogram (EEG) abnormalities specific to iRBD patients with MCI., Methods: Forty-two polysomnographically confirmed iRBD patients, including 23 iRBD [+]MCI patients 19 patients without MCI (iRBD [-]MCI), and 37 healthy subjects participated in the study. All participants underwent a complete neuropsychologic assessment for MCI diagnosis and a waking quantitative EEG recording., Results: iRBD [+]MCI patients had a higher slow-to-fast frequency ratio than iRBD [-]MCI patients and controls in the parietal, temporal, and occipital regions. iRBD [+]MCI patients also had higher relative θ power in the parietal, temporal, and occipital regions and lower relative α power in the occipital region compared to iRBD [-]MCI patients and controls. Moreover, iRBD [+]MCI patients had higher relative θ power in the frontal and central areas and lower relative β power in the central, parietal, and temporal regions compared to controls. The dominant occipital frequency also was slower in iRBD [+]MCI patients compared to controls. No between-group differences were observed between iRBD [-]MCI patients and controls., Conclusion: In iRBD patients, only those with concomitant MCI showed waking EEG slowing in the posterior cortical regions, providing a potential marker for an increased risk for developing DLB or PD., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Mild cognitive impairment (MCI) can occur early in the course of Parkinson's disease (PD), and its presence increases the risk of developing dementia. Determining the cortical changes associated with MCI in PD, thus, may be useful in predicting the future development of dementia. To address this objective, 37 patients with PD, divided into 2 groups according to the presence or absence MCI (18 with and 19 without) and 16 matched controls, underwent anatomic magnetic resonance imaging. Corticometry analyses were performed to measure the changes in cortical thickness and surface area as well as their correlation with disease duration. Compared with healthy controls, the PD-MCI group exhibited increased atrophy and changes of local surface area in the bilateral occipital, left temporal, and frontal cortices; whereas the PD non-MCI group exhibited only unilateral thinning and decreased surface area in the occipital lobe and in the frontal cortex. In addition, a comparison between the PD-MCI and PD non-MCI groups revealed increased local surface area in the occipital lobe, temporal lobe, and postcentral gyrus for the cognitively impaired patients. It is noteworthy that, in the PD-MCI group, cortical thickness had a significant negative correlation with disease duration in the precentral, supramarginal, occipital, and superior temporal cortices; whereas, in the PD non-MCI group, such a correlation was absent. The findings from this study reveal that, at the same stage of PD evolution, the presence of MCI is associated with a higher level of cortical changes, suggesting that cortical degeneration is increased in patients with PD because of the presence of MCI., (© 2013 International Parkinson and Movement Disorder Society.)

Background: Cognitive impairment is a frequent feature of COPD. However, the proportion of patients with COPD with mild cognitive impairment (MCI) is still unknown, and no screening test has been validated to date for detecting MCI in this population. The goal of this study was to determine the frequency and subtypes of MCI in patients with COPD and to assess the validity of two cognitive screening tests, the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA), in detecting MCI in patients with COPD., Methods: Forty-five patients with moderate to severe COPD and 50 healthy control subjects underwent a comprehensive neuropsychologic assessment using standard MCI criteria. Receiver operating characteristic curves were obtained to assess the validity of the MMSE and the MoCA to detect MCI in patients with COPD., Results: MCI was found in 36% of patients with COPD compared with 12% of healthy subjects. Patients with COPD with MCI had mainly the nonamnestic MCI single domain subtype with predominant attention and executive dysfunctions. The optimal MoCA screening cutoff was 26 (≤ 25 indicates impairment, with 81% sensitivity, 72% specificity, and 76% correctly diagnosed). No MMSE cutoff had acceptable validity., Conclusions: In this preliminary study, a substantial proportion of patients with COPD were found to have MCI, a known risk factor for dementia. Longitudinal follow-up on these patients is needed to determine the risk of developing more severe cognitive and functional impairments. Moreover, the MoCA is superior to the MMSE in detecting MCI in patients with COPD.