Childhood cognitive skill trajectories and suicide by mid-adulthood: an investigation of the 1958 British Birth Cohort.

BACKGROUND: Poor cognitive abilities and low intellectual quotient (IQ) are associated with an increased risk of suicide attempts and suicide mortality. However, knowledge of how this association develops across the life-course is limited. Our study aims to establish whether individuals who died by suicide by mid-adulthood are distinguishable by their child-to-adolescence cognitive trajectories. METHODS: Participants were from the 1958 British Birth Cohort and were assessed for academic performance at ages 7, 11, and 16 and intelligence at 11 years. Suicides occurring by September 2012 were identified from linked national death certificates. We compared mean mathematics and reading abilities and rate of change across 7-16 years for individuals who died by suicide v. those still alive, with and without adjustment for potential early-life confounding factors. Analyses were based on 14 505 participants. RESULTS: Fifty-five participants (48 males) had died by suicide by age 54 years. While males who died by suicide did not differ from participants still alive in reading scores at age 7 [effect size (g) = -0.04, p = 0.759], their reading scores had a less steep improvement up to age 16 compared to other participants. Adjustments for early-life confounding factors explained these differences. A similar pattern was observed for mathematics scores. There was no difference between individuals who died by suicide v. participants still alive on intelligence at 11 years. CONCLUSIONS: While no differences in tests of academic performance and IQ were observed, individuals who died by suicide had a less steep improvement in reading abilities over time compared to same-age peers.

Psychological pain and depression: it's hard to speak when it hurts.

OBJECTIVE: To investigate the neuropsychological features of depressed patients reporting high level of psychological pain. METHODS: Sixty-two inpatients were included and divided into two groups according to the level of psychological pain assessed by a Likert scale. Cognitive abilities were assessed using the Trail Making Test, the Stroop test, and Verbal Fluency Test (semantic and phonemic verbal fluency). Univariate and multivariate analyses were performed to determine neuropsychological factors associated with a high level of psychological pain. RESULTS: The median level of psychological pain was 8/10. High level of psychological pain was associated with poor phonemic verbal fluency performance in men (p = 0.009), but not in women, even after controlling for confounding factors (age, level of depression, anxiety). Groups did not differ on the Trail Making Test, the Stroop test, or the semantic verbal fluency measure. CONCLUSION: Psychological pain is a specific clinical entity that should be considered to be more significant than just a symptom of depression. High level of psychological pain appears to be associated with a deficit of phonemic verbal fluency in depressed men. This finding could help to target psychotherapeutic treatments and improve screening.Key pointsPatients with high psychological pain do not differ on the Trail Making Test, the Stroop Test or the Sematic Verbal Fluency Measure to patients with low psychological painHigh psychological pain is associated with a deficit in phonemic verbal fluency in depressed menFuture research should aim to clarify gender differences in psychological pain in participants with and without major depressive disorder, as well as explore the complex relationship between cognition and the different forms of pain (psychological, physical and psychosomatic).

Suicidal ideation is common in autosomal dominant Alzheimer's disease at-risk persons.

OBJECTIVES: To study the frequency of suicidal ideation and its association with clinical and neurobiological correlates among cognitively intact autosomal dominant Alzheimer's disease (ADAD) at-risk individuals. METHODS/DESIGN: In a cross-sectional study of 183 ADAD at-risk individuals (91 mutation carriers and 92 noncarriers), we compared the frequency of suicidal ideation among carriers and noncarriers. Linear mixed-effects models with family-level random effects evaluated the relationships between geriatric depression scale (GDS), neuropsychiatric inventory-questionnaire (NPI-Q), and suicidal ideation scores among all ADAD at-risk individuals. An interaction term was added to the regression models to evaluate the interactions of suicidal ideation and mutation status on neuropsychiatric symptoms. RESULTS: Twenty-six (14.20%) ADAD at-risk individuals (13 [14.28%] carriers and 13 [14.13%] noncarriers) had suicidal ideation. The frequency of suicidal ideation did not differ between carriers and noncarriers. Suicidal ideation was associated with higher GDS among all ADAD at-risk individuals. When stratified into mutation carrier status, noncarriers with suicidal ideation had higher GDS than carriers. There was no statistically significant association between suicidal ideation and NPI-Q among ADAD at-risk individuals. Awareness of mutation status, neuropsychological performances, and cerebrospinal fluid AD biomarkers were not associated with suicidal ideation among carriers and noncarriers. CONCLUSIONS: Suicidal ideation is common among cognitively intact ADAD at-risk individuals. While ADAD at-risk individuals with suicidal ideation have greater depressive symptoms, noncarriers with suicidal ideation have higher GDS scores than carriers. Interestingly, awareness of the mutation status was not associated with suicidal ideation in our study. Early identification of suicidal thoughts can facilitate timely interventions to prevent suicidal behaviours. Keywords autosomal dominant Alzheimer's diseasedominantly inherited Alzheimer's networkneuropsychiatric symptomssuicidal ideation.

Social support and sleep quality in older benzodiazepine users.

Objective: Benzodiazepines (BZD) are often prescribed to address sleep difficulties but many BZD users report a poor quality of sleep. Although social support was found to be associated with quality of sleep in a recent meta-analysis, this relationship was never studied in older BZD users. This study thus aims to examine how social support is associated with quality of sleep in older BZD users.Method: Seventy-two older adults (age 60-85) using BZD were recruited. Data was collected during the pre-test of the ''PASSE-60+; Support program for a successful withdrawal, NCT02281175'' study. Quality of sleep was measured using the Pittsburgh Sleep Quality Index (PSQI), while social support was evaluated with the Social Support Questionnaire (SSQ-6).Results: When examining the various dimensions of self-reported sleep quality as a whole, we found no significant association with social support, while controlling for daily BZD dose, anxiety and depression. However, we found a significant association between self-reported diurnal dysfunctions (e.g., daytime sleepiness) and satisfaction with social support.Conclusion: Although the results of our study should be replicated with larger samples, they might indicate that social support is not a significant factor influencing sleep quality in older chronic BZD users. Our results could differ from those found in other populations because of the changes in sleep quality associated with long term BZD use. Longitudinal studies should analyse the relationship between diurnal dysfunctions and satisfaction with social support, to examine if social support could help older adults alleviate their diurnal dysfunctions and eventually facilitate BZD tapering.

Clinical Utility of the Envelope Task in Mild Cognitive Impairment and Dementia.

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.

The Association between Generalized Anxiety Disorder, Subthreshold Anxiety Symptoms and Fear of Falling among Older Adults: Preliminary Results from a Pilot Study.

OBJECTIVE: A relationship between generalized anxiety disorder (GAD) and fear of falling (FOF) has long been proposed but never specifically studied. This study aimed at analyzing the relationship between FOF and GAD or anxiety symptoms, while controlling for major depressive episodes (MDE), depressive symptoms, fall risk, and sociodemographic variables. METHODS: Twenty-five older adults participated in this pilot study. Assessments included the following: Anxiety Disorder Interview Schedule, Geriatric Anxiety Inventory, Geriatric Depression Scale, Falls-Efficacy Scale-International. A multidisciplinary team evaluated fall risk. RESULTS: FOF was significantly correlated with GAD, MDE, anxiety and depressive symptoms, and fall risk, but not with sociodemographic variables. Multiple regression analyses indicated that GAD and anxiety symptoms were significantly and independently associated with FOF. CONCLUSION: Although the results of this pilot study should be replicated with larger samples, they suggest that FOF is associated with GAD and anxiety symptoms even when considering physical factors that increase the risk of falling. CLINICAL IMPLICATIONS: Treatment of FOF in patients with GAD may present a particular challenge because of the central role of intolerance of uncertainty, which may prevent patients from regaining confidence despite the reduction of fall risk. Clinicians should screen for GAD and anxiety symptoms in patients with FOF to improve detection and treatment.

Recognizing an object from the sum of its parts: an intracranial study on alpha rhythms.

Little is known about the relation of alpha rhythms and object recognition. Alpha has been generally proposed to be associated with attention and memory and to be particularly important for the mediation of long-distance communication between neuronal populations. However, how these apply to object recognition is still unclear. This study aimed at describing the spatiotemporal dynamics of alpha rhythms while recognizing fragmented images of objects presented for the first time and presented again 24 hr later. Intracranial electroencephalography was performed in six epileptic patients undergoing presurgical evaluation. Time-frequency analysis revealed a strong alpha activity, mainly of the evoked type, propagating from posterior cerebral areas to anterior regions, which was similar whether the objects were recognized or not. Phase coherence analysis, however, showed clear phase synchronization specific for the moment of recognition. Twenty-four hr later, frontal regions displayed stronger alpha activity and more distributed phase synchronization than when images were presented for the first time. In conclusion, alpha amplitude seems to be related to nonspecific mechanism. Phase coherence analysis suggests a communicational role of alpha activity in object recognition, which may be important for the comparison between bottom-up representations and memory templates.

The profession of neuropsychologist in Canada: Findings of a national survey.

The purpose of this study was to investigate the demographic characteristics, academic training and types of professional activities of clinical neuropsychologists in Canada.282 participants completed an online-based survey.Respondents were women for the most part and had a mean age of 43 years. They typically had doctoral-level training (85%) and about one-quarter had postdoctoral training (23%). Nearly half (47%) had a lifespan practice, over one-third (37%) had an adults-only practice, and about one-sixth (16%) had an exclusively pediatric practice. Most worked full-time (79%). Respondents were almost evenly split three ways between those who worked in the public sector, those who worked in the private sector, and those who worked in both. The most common professional activities related to assessment (95%), although clinical supervision (43%) and rehabilitation (42%) were also quite frequent, whereas research (27%) and teaching (18%) were less so. The most common reason for referral was to determine a diagnosis (79%). Pediatric neuropsychologists worked primarily with individuals with neurodevelopmental disorders and neuropsychologists working with adult populations worked primarily with individuals with emotional disorders, acquired neuropsychological disorders (traumatic brain injury, stroke/vascular), and neurocognitive disorders (dementia).At time of study, Canadian neuropsychologists seemed to enjoy a fairly balanced situation: Their level of training and the ratio of neuropsychologists per population were both high. However, these varied widely across Canada. This suggests that the profession and public interest would stand to gain from seeing training standardized to some extent nationwide.

Color discrimination deficits in Parkinson's disease are related to cognitive impairment and white-matter alterations.

Color discrimination deficit is a common nonmotor manifestation of Parkinson's disease (PD). However, the pathophysiology of this dysfunction remains poorly understood. Although retinal structure changes found in PD have been suggested to cause color discrimination deficits, the impact of cognitive impairment and cortical alterations remains to be determined. We investigated the contribution of cognitive impairment to color discrimination deficits in PD and correlated them with cortical anomalies. Sixty-six PD patients without dementia and 20 healthy controls performed the Farnsworth-Munsell 100 hue test and underwent a comprehensive neuropsychological assessment for mild cognitive impairment diagnosis. In a subgroup of 26 PD patients, we also used high-definition neuroanatomical magnetic resonance imaging for cortical thickness and diffusion tensor analysis. PD patients with mild cognitive impairment performed poorly on the Farnsworth-Munsell 100 hue test compared with PD patients without mild cognitive impairment and controls. In PD patients, performance on the Farnsworth-Munsell 100 hue test was correlated with measures of visuospatial abilities and executive functions. Neuroimaging analysis revealed higher mean and radial diffusivity values in right posterior white-matter structures that correlated with poor performance on the Farnsworth-Munsell 100 hue test. No cortical thickness correlation reached significance. This study showed that cognitive impairment makes a major contribution to the color discrimination deficits reported in PD. Thus, performance on the Farnsworth-Munsell 100 hue test may reflect cognitive impairment more than color discrimination deficits in PD. Poor performance on the Farnsworth-Munsell 100 hue test was also associated with white-matter alterations in right posterior brain regions.

Rapid eye movement sleep behavior disorder and risk of dementia in Parkinson's disease: a prospective study.

One of the most devastating nonmotor manifestations of PD is dementia. There are few established predictors of dementia in PD. In numerous cross-sectional studies, patients with rapid eye movement (REM) sleep behavior disorder (RBD) have increased cognitive impairment on neuropsychological testing, but no prospective studies have assessed whether RBD can predict Parkinson's dementia. PD patients who were free of dementia were enrolled in a prospective follow-up of a previously published cross-sectional study. All patients had a polysomnogram at baseline. Over a mean 4-year follow-up, the incidence of dementia was assessed in those with or without RBD at baseline using regression analysis, adjusting for age, sex, disease duration, and follow-up duration. Of 61 eligible patients, 45 (74%) were assessed and 42 were included in a full analysis. Twenty-seven patients had baseline RBD, and 15 did not. Four years after the initial evaluation, 48% with RBD developed dementia, compared to 0% of those without (P-adjusted = 0.014). All 13 patients who developed dementia had mild cognitive impairment on baseline examination. Baseline REM sleep atonia loss predicted development of dementia (% tonic REM = 73.2 ± 26.7 with dementia, 40.8 ± 34.5 without; P = 0.029). RBD at baseline also predicted the new development of hallucinations and cognitive fluctuations. In this prospective study, RBD was associated with increased risk of dementia. This indicates that RBD may be a marker of a relatively diffuse, complex subtype of PD.

An intracranial event-related potential study on transformational apparent motion. Does its neural processing differ from real motion?

How the brain processes visual stimuli has been extensively studied using scalp surface electrodes and magnetic resonance imaging. Using these and other methods, complex gratings have been shown to activate the ventral visual stream, whereas moving stimuli preferentially activate the dorsal stream. In the current study, a first experiment assessed brain activations evoked by complex gratings using intracranial electroencephalography in 10 epileptic patients implanted with subdural electrodes. These stimuli of intermediate levels of complexity were presented in such a way that transformational apparent motion (TAM) was perceived. Responses from both the ventral and the dorsal pathways were obtained. The response characteristics of visual area 4 and the fusiform cortex were of similar amplitudes, suggesting that both ventral areas are recruited for the processing of complex gratings. On the other hand, TAM-induced responses of dorsal pathway areas were relatively noisier and of lower amplitudes, suggesting that TAM does not activate motion-specific structures to the same extent as does real motion. To test this hypothesis, we examined the activity evoked by TAM in comparison to the one produced by real motion in a patient implanted with the same subdural electrodes. Findings demonstrated that neural response to real motion was much stronger than that evoked by TAM, in both the primary visual cortex (V1) and other motion-sensitive areas within the dorsal pathway. These results support the conclusion that apparent motion, even if perceptually similar to real motion, is not processed in a similar manner.

Electroencephalogram slowing predicts neurodegeneration in rapid eye movement sleep behavior disorder.

A large proportion of patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) develop a synucleinopathy, mostly Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Therefore, identifying markers of neurodegeneration in iRBD could have major implications. We aimed to assess the usefulness of electroencephalography (EEG) spectral analysis performed during wakefulness for predicting the development of a neurodegenerative disease in iRBD. Fifty-four iRBD patients, 28 of whom developed Parkinson's disease, multiple system atrophy, or dementia with Lewy bodies (mean follow-up: 3.5 years), and 30 healthy controls underwent at baseline a resting-state waking EEG recording, neurological exam, and neuropsychological assessment. Absolute and relative spectral powers were analyzed for 5 frequency bands in frontal, central, parietal, temporal, and occipital regions. The slow-to-fast [(δ + θ)/(ß1 + ß2)] power ratio for each of the 5 cortical regions and the dominant occipital frequency were calculated as an index of cortical slowing. Patients who developed disease showed higher absolute delta and theta power in all 5 cortical regions compared to disease-free patients and controls. The slow-to-fast power ratio was higher in all regions in patients who developed disease than in the 2 other groups. Moreover, patients who developed disease had a slower dominant occipital frequency compared to controls. The only significant difference observed between disease-free iRBD patients and controls was higher absolute delta power in frontal and occipital regions in iRBD patients. Specific EEG abnormalities were identified during wakefulness in iRBD patients who later developed a synucleinopathy. EEG slowing is a promising marker of neurodegeneration in iRBD patients.

Brain Connectivity Alterations Are Associated with the Development of Dementia in Parkinson's Disease.

Dementia affects a high proportion of Parkinson's disease (PD) patients and poses a burden on caregivers and healthcare services. Electroencephalography (EEG) is a common nonevasive and nonexpensive technique that can easily be used in clinical settings to identify brain functional abnormalities. Only few studies had identified EEG abnormalities that can predict PD patients at higher risk for dementia. Brain connectivity EEG measures, such as multiscale entropy (MSE) and phase-locking value (PLV) analyses, may be more informative and sensitive to brain alterations leading to dementia than previously used methods. This study followed 62 dementia-free PD patients for a mean of 3.4 years to identify cerebral alterations that are associated with dementia. Baseline resting state EEG of patients who developed dementia (N = 18) was compared to those of patients who remained dementia-free (N = 44) and of 37 healthy subjects. MSE and PLV analyses were performed. Partial least squares statistical analysis revealed group differences associated with the development of dementia. Patients who developed dementia showed higher signal complexity and lower PLVs in low frequencies (mainly in delta frequency) than patients who remained dementia-free and controls. Conversely, both patient groups showed lower signal variability and higher PLVs in high frequencies (mainly in gamma frequency) compared to controls, with the strongest effect in patients who developed dementia. These findings suggest that specific disruptions of brain communication can be measured before PD patients develop dementia, providing a new potential marker to identify patients at highest risk of developing dementia and who are the best candidates for neuroprotective trials.

Parkinson risk in idiopathic REM sleep behavior disorder: preparing for neuroprotective trials.

OBJECTIVE: To precisely delineate clinical risk factors for conversion from idiopathic REM sleep behavior disorder (RBD) to Parkinson disease, dementia with Lewy bodies, and multiple system atrophy, in order to enable practical planning and stratification of neuroprotective trials against neurodegenerative synucleinopathy. METHODS: In a 10-year prospective cohort, we tested prodromal Parkinson disease markers in 89 patients with idiopathic RBD. With Kaplan-Meier analysis, we calculated risk of neurodegenerative synucleinopathy, and using Cox proportional hazards, tested the ability of prodromal markers to identify patients at higher disease risk. By combining predictive markers, we then designed stratification strategies to optimally select patients for definitive neuroprotective trials. RESULTS: The risk of defined neurodegenerative synucleinopathy was high: 30% developed disease at 3 years, rising to 66% at 7.5 years. Advanced age (hazard ratio [HR] = 1.07), olfactory loss (HR = 2.8), abnormal color vision (HR = 3.1), subtle motor dysfunction (HR = 3.9), and nonuse of antidepressants (HR = 3.5) identified higher risk of disease conversion. However, mild cognitive impairment (HR = 1.8), depression (HR = 0.63), Parkinson personality, treatment with clonazepam (HR = 1.3) or melatonin (HR = 0.55), autonomic markers, and sex (HR = 1.37) did not clearly predict clinical neurodegeneration. Stratification with prodromal markers increased risk of neurodegenerative disease conversion by 200%, and combining markers allowed sample size reduction in neuroprotective trials by >40%. With a moderately effective agent (HR = 0.5), trials with fewer than 80 subjects per group can demonstrate definitive reductions in neurodegenerative disease. CONCLUSIONS: Using stratification with simply assessed markers, it is now not only possible, but practical to include patients with RBD in neuroprotective trials against Parkinson disease, multiple system atrophy, and dementia with Lewy bodies.

Sleep spindles in Parkinson's disease may predict the development of dementia.

Sleep disturbances and cognitive impairment are common non-motor manifestations of Parkinson's disease (PD). Recent studies suggest that sleep spindles and slow waves play a role in brain plasticity mechanisms and are associated with cognitive performance. However, it remains unknown whether these sleep parameters could serve as markers of cognitive decline in PD. Therefore, we examined whether alterations in sleep spindles and slow waves at baseline visit were associated with increased likelihood of developing dementia at follow-up in PD. Sixty-eight nondemented PD patients (64.9 ± 8.8 years old; 46 men) participated in the study, along with 47 healthy individuals (65.0 ± 10.6 years old; 30 men). All participants underwent baseline polysomnographic recording and a comprehensive neuropsychological assessment. Sleep spindles (12-15 Hz) and slow waves (>75 µV and <4 Hz) were automatically detected on all-night non-rapid eye movement sleep electroencephalography. At follow-up (mean: 4.5 years later), 18 PD patients developed dementia (70.2 ± 7.6 years old; 13 men) and 50 remained dementia-free (63.0 ± 8.5 years old; 33 men). Sleep spindle density and amplitude were lower in PD patients who converted to dementia compared with both patients who remained dementia-free and controls, mostly in posterior cortical regions (p < 0.05). Dementia-free PD patients were intermediate between dementia patients and controls, with lower baseline sleep spindle density in all cortical areas compared with controls (p < 0.01). In demented PD patients, lower sleep spindle amplitude in parietal and occipital areas was associated with poorer visuospatial abilities. Although slow wave amplitude was lower in PD patients compared with controls (p < 0.0001), no difference was observed between those who developed or did not develop dementia. Results demonstrate non-rapid eye movement sleep electroencephalographic abnormalities in PD patients. Sleep spindle activity was particularly impaired in PD patients who developed dementia, with a more posterior topographic pattern. Sleep spindle alterations are associated with later development of dementia in PD, and thus may serve as an additional marker of cognitive decline in these patients.

Observational Study of the Relation between Parkinson's Disease and Sleep Apnea.

BACKGROUND: Parkinson's disease is characterized by numerous non-motor symptoms, including sleep disorders. Sleep apnea has been reported in a substantial proportion of patients with Parkinson's disease, but it is unclear whether it has significant consequences for the quality of life of those affected or whether it is associated with other manifestations of the disease. OBJECTIVE: To verify whether sleep apnea is associated with more severe motor and non-motor clinical features in Parkinson's disease. METHODS: Parkinson's disease patients underwent polysomnography to diagnose the presence of sleep apnea (apnea-hypopnoea index >10). Participants also underwent an extensive assessment, blinded to sleep apnea status, to determine disease severity, quantitative motor indices, motor subtypes, treatment complications, and sleep, autonomic, psychiatric, and sensory dysfunctions. Cognitive status was also determined with a complete neuropsychological assessment. Results were assessed using regression analysis adjusted for age, sex, and disease duration. RESULTS: Of 92 patients examined, 19 had sleep apnea (21%) and 73 did not. We found no significant differences in motor and non-motor symptoms or signs between apneic and non-apneic Parkinson's disease patients. The use of different apnea-hypopnoea index cut-offs (>5 and >15) produced similar results. CONCLUSIONS: Our results show that sleep apnea is not associated with more severe motor or non-motor manifestations in Parkinson's disease. More studies including control groups are needed to confirm the implications of those results.

Predictors of dementia in Parkinson disease: a prospective cohort study.

OBJECTIVE: We investigated an array of possible markers of early dementia in Parkinson disease. METHODS: We performed a comprehensive assessment of autonomic, sleep, psychiatric, visual, olfactory, and motor manifestations in 80 patients with Parkinson disease who were dementia-free at baseline. After 4.4 years' follow-up, patients were evaluated for dementia. Predictive variables were assessed using logistic regression adjusting for disease duration, follow-up duration, age, and sex. RESULTS: Of 80 patients, 27 (34%) developed dementia. Patients destined to develop dementia were older and more often male (odds ratio [OR] = 3.64, p = 0.023). Those with baseline mild cognitive impairment had increased dementia risk (OR = 22.5, p < 0.001). REM sleep behavior disorder at baseline dramatically increased dementia risk (OR = 49.7, p = 0.001); however, neither daytime sleepiness nor insomnia predicted dementia. Higher baseline blood pressure increased dementia risk (OR = 1.37 per 10 mm Hg, p = 0.032). Orthostatic blood pressure drop was strongly associated with dementia risk (OR = 1.84 per 10 mm Hg, p < 0.001); having a systolic drop of >10 mm Hg increased dementia odds 7-fold (OR = 7.3, p = 0.002). Abnormal color vision increased dementia risk (OR = 3.3, p = 0.014), but olfactory dysfunction did not. Among baseline motor variables, proportion of gait involvement (OR = 1.12, p = 0.023), falls (OR = 3.02, p = 0.042), and freezing (OR = 2.63, p = 0.013), as well as the Purdue Pegboard Test (OR = 0.67, p = 0.049) and alternate tap test (OR = 0.97, p = 0.033) predicted dementia. CONCLUSION: Cardiovascular autonomic dysfunction, REM sleep behavior disorder, color discrimination ability, and gait dysfunction strongly predict development of dementia in Parkinson disease.

Induced gamma-band response to fragmented images: An intracranial EEG study.

Induced gamma-band response (iGBR) has been linked to coherent perception of images and is thought to represent the synchronisation of neuronal populations mediating binding of elements composing the image and the comparisons with memory for proper recognition. This study uses fragmented images with intracranial electroencephalography to investigate the precise spatio-temporal dynamic of iGBR elicited by the recognition of objects presented for the first time and 24h later. Results show an increased iGBR at recognition in regions involved in bottom-up processes such as the cuneus and the lateral occipital complex. Top-down facilitation involved the lingual gyrus, the precuneus and the superior parietal lobule when images were presented for the first time. Twenty-four hours later, top-down facilitation was mediated by frontal areas involved in retrieval from episodic memory. This study showed that the classically reported iGBR is related to object recognition and that top-down processes vary according to task demand.

Electroencephalogram slowing in rapid eye movement sleep behavior disorder is associated with mild cognitive impairment.

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 ß 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.

Antidepressants and REM sleep behavior disorder: isolated side effect or neurodegenerative signal?

OBJECTIVES: Antidepressants, among the most commonly prescribed medications, trigger symptoms of REM sleep behavior disorder (RBD) in up to 6% of users. Idiopathic RBD is a very strong prodromal marker of Parkinson disease and other synuclein-mediated neurodegenerative syndromes. It is therefore critically important to understand whether antidepressant-associated RBD is an independent pharmacologic syndrome or a sign of possible prodromal neurodegeneration. DESIGN: Prospective cohort study. SETTING: Tertiary sleep disorders center. PARTICIPANTS: 100 patients with idiopathic RBD, all with diagnosis confirmed on polysomnography, stratified to baseline antidepressant use, with 45 matched controls. MEASUREMENTS/RESULTS: Of 100 patients, 27 were taking antidepressants. Compared to matched controls, RBD patients taking antidepressants demonstrated significant abnormalities of 12/14 neurodegenerative markers tested, including olfaction (P = 0.007), color vision (P = 0.004), Unified Parkinson Disease Rating Scale II and III (P < 0.001 and 0.007), timed up-and-go (P = 0.003), alternate tap test (P = 0.002), Purdue Pegboard (P = 0.007), systolic blood pressure drop (P = 0.029), erectile dysfunction (P = 0.002), constipation (P = 0.003), depression indices (P < 0.001), and prevalence of mild cognitive impairment (13% vs. 60%, P < 0.001). All these abnormalities were indistinguishable in severity from RBD patients not taking antidepressants. However, on prospective follow-up, RBD patients taking antidepressants had a lower risk of developing neurodegenerative disease than those without antidepressant use (5-year risk = 22% vs. 59%, RR = 0.22, 95%CI = 0.06, 0.74). CONCLUSIONS: Although patients with antidepressant-associated RBD have a lower risk of neurodegeneration than patients with "purely-idiopathic" RBD, markers of prodromal neurodegeneration are still clearly present. Development of RBD with antidepressants can be an early signal of an underlying neurodegenerative disease.