Quantifying Apathy in Late-Life Depression: Unraveling Neurobehavioral Links through Daily Activity Patterns and Brain Connectivity Analysis.

BACKGROUND: Better understanding apathy in late-life depression (LLD) would help predicting poor prognosis of the disease such as dementia. Actimetry provides an objective and ecological measure of apathy from patients' daily motor activity. We aimed to determine if patterns of motor activity were associated with apathy and brain connectivity in networks underlying goal-directed behaviors. METHODS: Resting-state functional MRI and diffusion MRI were collected from 38 non-demented LLD subjects. Apathy was evaluated using the diagnostic criteria for apathy, the apathy evaluation scale (AES) and the apathy motivation index (AMI). Functional principal components (fPC) of motor activity were derived from actimetry recordings of 72 hours. Associations between fPC and apathy were estimated by linear regression. Subnetworks whose connectivity was significantly associated with fPC were identified via the threshold-free network-based statistics. The relationship between apathy and microstructure metrics was estimated along fibers by diffusion tensor imaging and a multicompartment model called neurite orientation dispersion and density imaging via tractometry. RESULTS: We found two fPC associated with apathy: mean diurnal activity, negatively associated with AES, and an early chronotype, negatively associated with AMI. Mean diurnal activity was associated with increased connectivity in the default-mode, the cingulo-opercular and the frontoparietal networks, while chronotype was associated with a more heterogenous connectivity pattern in the same networks. We did not find significant associations between microstructural metrics and fPCs. CONCLUSION: Our findings suggest that mean diurnal activity and chronotype could provide indirect ambulatory measures of apathy in LLD, associated with modified functional connectivity of brain networks underlying goal-directed behaviors.

Connectivity patterns of the core resting-state networks associated with apathy in late-life depression.

BACKGROUND: Apathy is associated with reduced antidepressant response and dementia in late-life depression (LLD). However, the functional cerebral basis of apathy is understudied in LLD. We investigated the functional connectivity of 5 resting-state networks (RSN) hypothesized to underlie apathy in LLD. METHODS: Resting-state functional MRI data were collected from individuals with LLD who did not have dementia as well as healthy older adults between October 2019 and April 2022. Apathy was evaluated using the diagnostic criteria for apathy (DCA), the Apathy Evaluation Scale (AES) and the Apathy Motivation Index (AMI). Subnetworks whose connectivity was significantly associated with each apathy measure were identified via the threshold-free network-based statistics. Regions that were consistently associated with apathy across the measures were reported as robust findings. RESULTS: Our sample included 39 individuals with LLD who did not have dementia and 26 healthy older adults. Compared with healthy controls, individuals with LLD had an altered intra-RSN and inter-RNS connectivity in the default mode, the cingulo-opercular and the frontoparietal networks. All 3 apathy measurements showed associations with modified intra-RSN connectivity in these networks, except for the DCA in the cingulo-opercular network. The AMI scores showed stronger associations with the cingulo-opercular and frontoparietal networks, whereas the AES had stronger associations with the default mode network and the goal-oriented behaviour network. LIMITATIONS: The study was limited by the small number of participants without apathy according to the DCA, which may have reduced the statistical power of between-group comparisons. Additionally, the reliance on specific apathy measures may have influenced the observed overlap in brain regions. CONCLUSION: Our findings indicate that apathy in LLD is consistently associated with changes in both intra-RSN and inter-RSN connectivity of brain regions implicated in goal-oriented behaviours. These results corroborate previous findings of altered functional RSN connectivity in severe LLD.

[Alzheimer's disease, amyloid-b peptides and ubiquitin-proteasome system: Therapeutic perspectives]. / Maladie d'Alzheimer, peptides ß-amyloïdes et système ubiquitine-protéasome - Perspectives thérapeutiques.

The Alzheimer's disease - an age-related neurodegenerative disorder leading to a progressive cognitive impairment - is characterized by an intracerebral accumulation of soluble ß-amyloid (Aß) oligomers, followed by the appearance of abnormally ubiquitinylated neurofibrillary tangles - a process associated with a chronic inflammation. The systematic presence of ubiquitinylated inclusions reflects a decrease in the proteasome activity due to (and contributing to) the presence of Aß oligomers - a central dysfunction in the etiology of the disease. The involvement of the ubiquitin-proteasome system opens new therapeutic perspectives for both prevention and treatment.

Title: Maladie d'Alzheimer, peptides ß-amyloïdes et système ubiquitine-protéasome - Perspectives thérapeutiques. Abstract: La maladie d'Alzheimer ­ une maladie neurodégénérative liée à l'âge entraînant une altération progressive des fonctions cognitives ­ se caractérise par une accumulation intracérébrale d'oligomères ß-amyloïdes (Aß) solubles, suivie d'une apparition d'enchevêtrements neurofibrillaires anormalement ubiquitinylés ­ un processus associé à une inflammation chronique. La présence systématique d'inclusions ubiquitinylées traduit une baisse d'activité du protéasome due (et concourant) à la présence d'oligomères Aß ­ un dysfonctionnement central dans l'étiologie de la maladie. L'implication du système ubiquitine-protéasome ouvre de nouvelles perspectives thérapeutiques tant préventives que curatives.

Different Trajectories of Apathy and Depression Among Subjective Cognitive Impairment Individuals with or without Conversion to Dementia: Results from the Memento Cohort in France.

BACKGROUND: Apathy and depression are two early behavioral symptoms in Alzheimer's disease (AD) and related disorders that often occur prior to the onset of cognitive decline and memory disturbances. Both have been associated with an increased risk of conversion to dementia, with a distinct neuropathology. OBJECTIVE: The assessment of the trajectories of apathy and depression and their independent impact on dementia conversion. METHODS: Apathy and Depression were measured using the Neuropsychiatric Inventory for caregiver (NPI) and clinician (NPI-C), among the nondemented individuals reporting subjective cognitive decline (SCD) at baseline. They were followed up over a 60-month period. Some converted to dementia, according to the methodology carried out by the French Memento Cohort. RESULTS: Among individuals with SCD (n = 2,323), the levels of apathy and depression were low and did not evolve significantly over the 60-month period, despite a trend in apathy increasing as of month 24. Regarding SCD individuals who converted to dementia within the 60-month period (n = 27), the prevalence of depression remained globally steady, while the levels of apathy increased over time. CONCLUSION: Apathy and depression have different trajectories among individuals with SCD and apathy alone is more likely-compared to depression-to be associated with conversion to dementia.

Assessing the pool activity level (PAL) checklist for use with people with hearing and vision loss.

BACKGROUND: The PAL is a career-completed assessment that indexes cognitive functional ability to inform individualised support. As hearing and vision loss are prevalent, we assessed the PAL for potential bias with hearing or vision impairment. METHODS: We collected PAL responses for 333 adults aged over 60 years in the UK, France, Canada, Greece and Cyprus. All participants had normal cognition based on self-reported status and normal range scores on a cognitive screening test. Using a Kruskal-Wallis test, we compared PAL item response distributions for people with assessed hearing or vision loss compared to those with normal sensory function. RESULTS: There were no differences in response distributions between hearing or vision impaired groups versus those with normal sensory function on any PAL item. CONCLUSION: The PAL reliably indexes cognitive functional ability and may be used to inform support tailored to individual cognitive level amongst older adults with prevalent hearing and vision impairments.

Physical activity, biomarkers of brain pathologies and dementia risk: Results from the Memento clinical cohort.

INTRODUCTION: This study aims to examine whether physical activity moderates the association between biomarkers of brain pathologies and dementia risk. METHODS: From the Memento cohort, we analyzed 1044 patients with mild cognitive impairment, aged 60 and older. Self-reported physical activity was assessed using the International Physical Activity Questionnaire. Biomarkers of brain pathologies comprised medial temporal lobe atrophy (MTA), white matter lesions, and plasma amyloid beta (Aß)42/40 and phosphorylated tau181. Association between physical activity and risk of developing dementia over 5 years of follow-up, and interactions with biomarkers of brain pathologies were tested. RESULTS: Physical activity moderated the association between MTA and plasma Aß42/40 level and increased dementia risk. Compared to participants with low physical activity, associations of both MTA and plasma Aß42/40 on dementia risk were attenuated in participants with high physical activity. DISCUSSION: Although reverse causality cannot be excluded, this work suggests that physical activity may contribute to cognitive reserve. HIGHLIGHTS: Physical activity is an interesting modifiable target for dementia prevention. Physical activity may moderate the impact of brain pathology on dementia risk. Medial temporal lobe atrophy and plasma amyloid beta 42/40 ratio were associated with increased dementia risk especially in those with low level of physical activity.

Development and validation of the Montreal cognitive assessment for people with hearing impairment (MoCA-H).

BACKGROUND: Hearing impairment is common among older adults and affects cognitive assessments for identification of dementia which rely on good hearing function. We developed and validated a version of the Montreal Cognitive Assessment (MoCA) for people with hearing impairment. METHODS: We adapted existing MoCA 8.1 items for people with hearing impairment by presenting instructions and stimuli in written rather than spoken format. One Attention domain and two Language domain items required substitution by alternative items. Three and four candidate items respectively were constructed and field-tested along with the items adapted to written form. We used a combination of individual item analysis and item substitution to select the set of alternative items to be included in the final form of the MoCA-H in place of the excluded original items. We then evaluated the performance and reliability of the final tool, including making any required adjustments for demographic factors. RESULTS: One hundred and fifty-nine hearing-impaired participants, including 76 with normal cognition and 83 with dementia, completed the adapted version of the MoCA. A further 97 participants with normal hearing completed the standard MoCA as well as the novel items developed for the MoCA-H to assess score equivalence between the existing and alternative MoCA items and for independence from hearing impairment. Twenty-eight participants were retested between 2-4 weeks after initial testing. After the selection of optimal item set, the final MoCA-H had an area under the curve of 0.973 (95% CI 0.952-0.994). At a cut-point of 24 points or less sensitivity and specificity for dementia was 92.8% and 90.8%, respectively. The intraclass correlation for test-retest reliability was 0.92 (95%CI 0.78-0.97). CONCLUSION: The MoCA-H is a sensitive and reliable means of identifying dementia among adults with acquired hearing impairment.

Prodromal characteristics of dementia with Lewy bodies: baseline results of the MEMENTO memory clinics nationwide cohort.

BACKGROUND: Isolated subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) are the prodromal phases of dementia with Lewy bodies (DLB). MEMENTO is a nationwide study of patients with SCI and MCI with clinic, neuropsychology, biology, and brain imaging data. We aimed to compare SCI and MCI patients with symptoms of prodromal DLB to others in this study at baseline. METHODS: Participants of the French MEMENTO cohort study were recruited for either SCI or MCI. Among them, 892 were included in the Lewy sub-study, designed to search specifically for symptoms of DLB. Probable prodromal DLB diagnosis (pro-DLB group) was done using a two-criteria cutoff score among the four core clinical features of DLB. This Pro-DLB group was compared to two other groups at baseline: one without any core symptoms (NS group) and the one with one core symptom (1S group). A comprehensive cognitive battery, questionnaires on behavior, neurovegetative and neurosensory symptoms, brain 3D volumetric MRI, CSF, FDG PET, and amyloid PET were done. RESULTS: The pro-DLB group comprised 148 patients (16.6%). This group showed more multidomain (59.8%) MCI with slower processing speed and a higher proportion of patients with depression, anxiety, apathy, constipation, rhinorrhea, sicca syndrome, and photophobia, compared to the NS group. The pro-DLB group had isolated lower P-Tau in the CSF (not significant after adjustments for confounders) and on brain MRI widening of sulci including fronto-insular, occipital, and olfactory sulci (FDR corrected), when compared to the NS group. Evolution to dementia was not different between the three groups over a median follow-up of 2.6 years. CONCLUSIONS: Patients with symptoms of prodromal DLB are cognitively slower, with more behavioral disorders, autonomic symptoms, and photophobia. The occipital, fronto-insular, and olfactory bulb involvement on brain MRI was consistent with symptoms and known neuropathology. The next step will be to study the clinical, biological, and imaging evolution of these patients. TRIAL REGISTRATION: Clinicaltrials.gov , NCT01926249.

Top-down and bottom-up sources of eye-movement guidance during realistic scene search in Alzheimer's disease.

OBJECTIVE: Visual search is a crucial task in daily life, but in Alzheimer's disease (AD) it has usually been investigated using simple arrays. Here, we used scenes depicting real environments and studied the time course of attentional guidance. METHOD: We analyzed eye-movement differences between mild AD patients and age-matched healthy controls during search. We examined top-down guidance, manipulating the target template (precise picture vs. word cue) and the target-scene semantic consistency (consistent vs. inconsistent), and bottom-up guidance, manipulating the perceptual salience (high vs. low) of targets and distractors. RESULTS: During scene scanning, AD patients had longer search times, made more fixations before the first target fixation, and showed a greater probability of distractor selection, with longer distractor fixation. AD also led to longer target fixation. In patients and controls, picture cues and highly salient targets improved all search phases, whereas consistent targets only improved search initiation (first saccade). Moreover, top-down and bottom-up guidance interacted in initiation and scanning, and this did not differ between the two groups of participants. However, AD led to a smaller picture cue benefit in shortening distractor fixation and greater bottom-up search facilitation during scanning, where a high-salience target reduced the performance gap between patients and controls. CONCLUSIONS: Our study shows the importance of top-down and bottom-up guidance, and their integration, in improving search in AD patients. It suggests that precise target cues and, even more, highly salient targets may act as environmental supports that enhance attentional processing and search performance. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Explaining the association between social and lifestyle factors and cognitive functions: a pathway analysis in the Memento cohort.

BACKGROUND: This work aimed to investigate the potential pathways involved in the association between social and lifestyle factors, biomarkers of Alzheimer's disease and related dementia (ADRD), and cognition. METHODS: The authors studied 2323 participants from the Memento study, a French nationwide clinical cohort. Social and lifestyle factors were education level, current household incomes, physical activity, leisure activities, and social network from which two continuous latent variables were computed: an early to midlife (EML) and a latelife (LL) indicator. Brain magnetic resonance imaging (MRI), lumbar puncture, and amyloid-positron emission tomography (PET) were used to define three latent variables: neurodegeneration, small vessel disease (SVD), and AD pathology. Cognitive function was defined as the underlying factor of a latent variable with four cognitive tests. Structural equation models were used to evaluate cross-sectional pathways between social and lifestyle factors and cognition. RESULTS: Participants' mean age was 70.9 years old, 62% were women, 28% were apolipoprotein-ε4 carriers, and 59% had a Clinical Dementia Rating (CDR) score of 0.5. Higher early to midlife social indicator was only directly associated with better cognitive function (direct ß = 0.364 (0.322; 0.405), with no indirect pathway through ADRD biomarkers (total ß = 0.392 (0.351; 0.429)). In addition to a direct effect on cognition (direct ß = 0.076 (0.033; 0.118)), the association between latelife lifestyle indicator and cognition was also mostly mediated by an indirect effect through lower neurodegeneration (indirect ß = 0.066 (0.042; 0.090) and direct ß = - 0.116 (- 0.153; - 0.079)), but not through AD pathology nor SVD. CONCLUSIONS: Early to midlife social factors are directly associated with higher cognitive functions. Latelife lifestyle factors may help preserve cognitive functions through lower neurodegeneration.

Mindfulness as a Protective Factor Against Increased Tobacco and Alcohol Use in Hospital Workers Following the First COVID-19-Related Lockdown: a Study in Southern France.

COVID-19-related national lockdowns worldwide have had repercussions on people's well-being and have led to increased substance use. Mindfulness has previously been associated with reduced psychological distress and benefits in terms of addictive behaviors. We aimed to assess whether dispositional mindfulness protected against increased tobacco and alcohol use in hospital workers after France's first lockdown started. All workers in two French hospitals were contacted by email to participate in an online survey. Three hundred eighty-five workers answered. We ran two separate logistic regression models to test for associations between the level of dispositional mindfulness and both increased tobacco and alcohol use, after adjusting for affect deterioration. Dispositional mindfulness was associated with a lower likelihood of increased tobacco (adjusted odds ratio (AOR) [95% CI] 0.71 [0.51; 0.99], p = 0.046) and alcohol (0.66 [0.50; 0.87], p = 0.004) use. The effect of mindfulness on tobacco use was partially mediated by affect deterioration. Dispositional mindfulness appeared to be a protective factor against lockdown-related tobacco and alcohol use increases in French hospital workers.

Benzodiazepine use and neuroimaging markers of Alzheimer's disease in nondemented older individuals: an MRI and 18F Florbetapir PET study in the MEMENTO cohort.

Recent evidence suggests an association between benzodiazepines (BZDs) use and lower brain amyloid load, a hallmark of AD pathophysiology. Other AD-related markers include hippocampal atrophy, but the effect of BZDs on hippocampal volume remains unclear. We aimed at 1) replicating findings on BZDs use and brain amyloid load and 2) investigating associations between BZDs use and hippocampal volume, in the MEMENTO clinical cohort of nondemented older adults with isolated memory complaint or light cognitive impairment at baseline. Total Standardized Uptake Value Ratio (SUVR) of brain amyloid load and hippocampal volume (HV) were obtained, respectively, from 18F Florbetapir positron emission tomography (PET) and magnetic resonance imaging (MRI), and compared between BZD chronic users and nonusers using multiple linear regressions adjusted for age, sex, educational level, ApoE ε4 genotype, cognitive and neuropsychiatric assessments, history of major depressive episodes and antidepressant intake. BZD users were more likely to manifest symptoms of depression, anxiety and apathy. In the MRI subgroup, BZD users were also more frequently females with low education and greater clinical impairments as assessed with the clinical dementia rating scale. Short- versus long-acting BZDs, Z-drugs versus non-Z-drugs BZDs, as well as dose and duration of BZD use, were also considered in the analyses. Total SUVR and HV were significantly lower and larger, respectively, in BZD users (n = 38 in the PET subgroup and n = 331 in the MRI subgroup) than in nonusers (n = 251 in the PET subgroup and n = 1840 in the MRI subgroup), with a medium (Cohen's d = -0.43) and low (Cohen's d = 0.10) effect size, respectively. Short-acting BZDs and Z-drugs were more significantly associated with larger HV. We found no effect of dose and duration of BZD use. Our results support the involvement of the GABAergic system as a potential target for blocking AD-related pathophysiology, possibly via reduction in neuronal activity and neuroinflammation. Future longitudinal studies may confirm the causal effect of BZDs to block amyloid accumulation and hippocampal atrophy.

Psychological Distress and Tobacco Use Among Hospital Workers During COVID-19.

Background and Aims: This work aims to assess the impact of the COVID-19 pandemic on hospital workers' psychological parameters and attitudes toward substance use, before and during the French COVID-19 lockdown. Methods: An online survey was proposed to the staff of the University Hospital of Nice and Sainte-Marie psychiatric hospital in France from May 18 to June 6, 2020 assessing changes in daily habits, psychological distress and changes in substance use, including smoking. Results: A total of 702 respondents (80.3% female) filled out the survey. Overall, most of the workers reported increased stress, irritability, sadness, decreased motivation, and a worse quality of sleep after the beginning of the COVID-19 lockdown. Additionally, hospital workers who were more likely to use tobacco during the COVID-19 lockdown reported increased sadness (OR = 1.23, p < 0.001), loss of motivation (OR = 0.86, p < 0.05), alcohol consumption (OR = 3.12, p < 0.001), lower incomes (OR = 1.69, p < 0.05), living alone (OR = 1.77, p < 0.001) and doing less physical activity (OR = 0.36, p < 0.001). Conclusion: During the first lockdown, significant psychological changes (sadness, distress, irritability) associated with changes in tobacco use and physical activity were reported. Such results should encourage hospital leaders to implement dedicated policies to better accompany hospital workers' psychological distress.

Smell and taste changes are early indicators of the COVID-19 pandemic and political decision effectiveness.

In response to the COVID-19 pandemic, many governments have taken drastic measures to avoid an overflow of intensive care units. Accurate metrics of disease spread are critical for the reopening strategies. Here, we show that self-reports of smell/taste changes are more closely associated with hospital overload and are earlier markers of the spread of infection of SARS-CoV-2 than current governmental indicators. We also report a decrease in self-reports of new onset smell/taste changes as early as 5 days after lockdown enforcement. Cross-country comparisons demonstrate that countries that adopted the most stringent lockdown measures had faster declines in new reports of smell/taste changes following lockdown than a country that adopted less stringent lockdown measures. We propose that an increase in the incidence of sudden smell and taste change in the general population may be used as an indicator of COVID-19 spread in the population.

[Mindfulness meditation for family caregivers]. / La méditation de pleine conscience pour les aidants familiaux.

A significant proportion of elderly people suffering from neurodegenerative pathologies are cared for by an informal caregiver. From the earliest stages of the disease, the psychological and behavioural disorders of patients constitute stress and anxiety factors for their caregivers. Mindfulness meditation has proven its usefulness in the management of anxiety. A study proposes caregiver management based on a mindfulness meditation program.

Subjective cognitive and non-cognitive complaints and brain MRI biomarkers in the MEMENTO cohort.

INTRODUCTION: Subjective cognitive complaints may be a signature of preclinical stage Alzheimer's disease. However, the link between subjective cognitive and non-cognitive complaints and brain alterations remains unclear. METHODS: The relationship between cognitive and non-cognitive complaints and brain biomarkers, measured by structural magnetic resonance imaging, was investigated in 2056 participants of the MEMENTO cohort of outpatients, who were dementia-free at baseline. We assessed whether the cognitive status at inclusion or the presence of the apolipoprotein E gene variant (APOE) ε4 could modulate the association between the intensity of complaints and brain lesions. RESULTS: Smaller hippocampal volume was associated with higher memory complaints and discomfort in daily life. In APOE ε4 carriers, smaller whole-brain white matter and gray matter volumes and gyrification indices in several regions of interest of the parietal and temporal lobes, in the entorhinal and the para-hippocampal gyrus, were associated with higher memory complaint score. CONCLUSIONS: The intensity of subjective complaints in not only memory but discomfort in daily life was associated with brain degeneration markers. The presence of APOE ε4 modulated the relationships between subjective memory complaints and brain alterations.

Recommendations for the Nonpharmacological Treatment of Apathy in Brain Disorders.

Apathy is a common neuropsychiatric syndrome observed across many neurocognitive and psychiatric disorders. Although there are currently no definitive standard therapies for the treatment of apathy, nonpharmacological treatment (NPT) is often considered to be at the forefront of clinical management. However, guidelines on how to select, prescribe, and administer NPT in clinical practice are lacking. Furthermore, although new Information and Communication Technologies (ICT) are beginning to be employed in NPT, their role is still unclear. The objective of the present work is to provide recommendations for the use of NPT for apathy, and to discuss the role of ICT in this domain, based on opinions gathered from experts in the field. The expert panel included 20 researchers and healthcare professionals working on brain disorders and apathy. Following a standard Delphi methodology, experts answered questions via several rounds of web-surveys, and then discussed the results in a plenary meeting. The experts suggested that NPT are useful to consider as therapy for people presenting with different neurocognitive and psychiatric diseases at all stages, with evidence of apathy across domains. The presence of a therapist and/or a caregiver is important in delivering NPT effectively, but parts of the treatment may be performed by the patient alone. NPT can be delivered both in clinical settings and at home. However, while remote treatment delivery may be cost and time-effective, it should be considered with caution, and tailored based on the patient's cognitive and physical profile and living conditions.

Pathways to care for people with dementia: An international multicentre study.

OBJECTIVE: The aim of the present study was to characterize the clinical pathways that people with dementia (PwD) in different countries follow to reach specialized dementia care. METHODS: We recruited 548 consecutive clinical attendees with a standardized diagnosis of dementia, in 19 specialized public centres for dementia care in 15 countries. The WHO "encounter form," a standardized schedule that enables data concerning basic socio-demographic, clinical, and pathways data to be gathered, was completed for each participant. RESULTS: The median time from the appearance of the first symptoms to the first contact with specialist dementia care was 56 weeks. The primary point of access to care was the general practitioners (55.8%). Psychiatrists, geriatricians, and neurologists represented the most important second point of access. In about a third of cases, PwD were prescribed psychotropic drugs (mostly antidepressants and tranquillizers). Psychosocial interventions (such as psychological counselling, psychotherapy, and practical advice) were delivered in less than 3% of situations. The analyses of the "pathways diagram" revealed that the path of PwD to receiving care is complex and diverse across countries and that there are important barriers to clinical care. CONCLUSIONS: The study of pathways followed by PwD to reach specialized care has implications for the subsequent course and the outcome of dementia. Insights into local differences in the clinical presentations and the implementation of currently available dementia care are essential to develop more tailored strategies for these patients, locally, nationally, and internationally.

Absence of Relationship Between Self-Reported Sleep Measures and Amyloid Load in Elderly Subjects.

Objective: To determine the relationships between self-reported sleep profile and cortical amyloid load in elderly subjects without dementia. Methods: This cross-sectional study included 143 community-dwelling participants aged ≥70 years (median: 73 years [70-85]; 87 females) with spontaneous memory complaints but dementia-free. Sociodemographic characteristics, health status, neuropsychological tests, sleep, and 18F-florbetapir (amyloid) PET data were collected. The clinical sleep interview evaluated nighttime sleep duration, but also daytime sleep duration, presence of naps, and restless leg syndrome (RLS) at time of study. Validated questionnaires assessed daytime sleepiness, insomnia, and risk of sleep apnea. The cortical standardized uptake value ratio (SUVr) was computed across six cortical regions. The relationship between sleep parameters and SUVr (cut-off ratio>1.17 and tertiles) was analyzed using logistic regression models. Results: Amyloid-PET was positive in 40.6% of participants. Almost 40% were at risk for apnea, 13.5% had RLS, 35.5% insomnia symptoms, 22.1% daytime sleepiness, and 18.8% took sleep drugs. No significant relationship was found between positive amyloid PET and nighttime sleep duration (as a continuous variable, or categorized into <6; 6-7; ≥7 h per night). Logistic regression models did not show any association between SUVr and daytime sleep duration, 24-h sleep duration, naps, RLS, daytime sleepiness, insomnia symptoms, and sleep apnea risk (before and after adjustment for APOEε4 and depressive symptoms). Conclusion: Our study did not confirm the association between amyloid-PET burden, poor sleep quantity/quality in elderly population, suggesting that the interplay between sleep, and amyloid is more complex than described.

Benzodiazepine use and brain amyloid load in nondemented older individuals: a florbetapir PET study in the Multidomain Alzheimer Preventive Trial cohort.

It remains unclear whether benzodiazepines (BZDs) constitute a risk factor for Alzheimer's disease (AD). In this study, we investigated associations between chronic use of BZDs and brain amyloid load, a hallmark of AD, in 268 nondemented older individuals. F18-florbetapir positron emission tomography scans were performed to assess amyloid load as measured by standardized uptake value ratios, which were compared between chronic BZD users and nonusers using adjusted multiple linear regressions. Short- versus long-acting BZDs were also considered in the analyses. Standardized uptake value ratios were significantly lower in BZD users (n = 47) than in nonusers (n = 221), independent of multiple adjustments. The effect was stronger for short-acting BZDs than for long-acting BZDs. This is the first large clinical study showing a reduced brain amyloid load in chronic BZD users, especially with short-acting BZDs. Our results do not support the view of BZD use as a risk factor for AD and instead support the involvement of pharmacological mechanisms related to neuronal hyperactivity, neuroinflammation, and sleep quality as potential targets for blocking amyloid accumulation.