Sleep, 24-Hour Activity Rhythms, and Subsequent Amyloid-ß Pathology.

Importance: Sleep disturbances are common among older adults and have been associated with the development of Alzheimer disease (AD), such as amyloid-ß (Aß) pathology. For effective AD prevention, it is essential to pinpoint the specific disturbances in sleep and the underlying 24-hour activity rhythms that confer the highest risk of Aß deposition. Objective: To determine the associations of 24-hour activity rhythms and sleep with Aß deposition in adults without dementia, to evaluate whether disrupted 24-hour activity and sleep may precede Aß deposition, and to assess the role of the apolipoprotein E ε4 (APOE4) genotype. Design, Setting, and Participants: This was an observational cohort study using data from the Rotterdam Study. Of 639 participants without dementia who underwent Aß positron emission tomography (PET) from September 2018 to November 2021, 319 were included in the current study. Exclusion criteria were no APOE genotyping and no valid actigraphy data at the baseline visits from 2004 to 2006 or from 2012 to 2014. The mean (SD) follow-up was 7.8 (2.4) years. Data were analyzed from March 2023 to April 2024. Exposures: Actigraphy (7 days and nights, objective sleep, and 24-hour activity rhythms), sleep diaries (self-reported sleep), Aß42/40, phosphorylated tau (p-tau)181 and p-tau217 plasma assays, 18F-florbetaben PET (mean standard uptake value ratio [SUVR] in a large cortical region of interest), and APOE4 genotype. Main Outcomes and Measures: Association of objective and self-reported sleep and 24-hour activity rhythms at baseline with brain Aß PET burden at follow-up. Results: The mean (range) age in the study population was 61.5 (48-80) years at baseline and 69.2 (60-88) years at follow-up; 150 (47%) were women. Higher intradaily variability at baseline, an indicator of fragmented 24-hour activity rhythms, was associated with higher Aß PET burden at follow-up (ß, 0.15; bootstrapped 95% CI, 0.04 to 0.26; bootstrapped P = .02, false discovery rate [FDR] P = .048). APOE genotype modified this association, which was stronger in APOE4 carriers (ß, 0.38; bootstrapped 95% CI, 0.05 to 0.64; bootstrapped P = .03) compared to noncarriers (ß, 0.07; bootstrapped 95% CI, -0.04 to 0.18; bootstrapped P = .19). The findings remained largely similar after excluding participants with AD pathology at baseline, suggesting that a fragmented 24-hour activity rhythm may have preceded Aß deposition. No other objective or self-reported measure of sleep was associated with Aß. Conclusions and Relevance: Among community-dwelling adults included in this study, higher fragmentation of the 24-hour activity rhythms was associated with greater subsequent Aß burden, especially in APOE4 carriers. These results suggest that rest-activity fragmentation could represent a modifiable risk factor for AD.

Mechanisms Linking Physical Activity with Psychiatric Symptoms Across the Lifespan: A Systematic Review.

BACKGROUND: Physical activity has been suggested as a protective factor against psychiatric symptoms. While numerous studies have focused on the magnitude of physical activity's effect on psychiatric symptoms, few have examined the potential mechanisms. OBJECTIVE: The current review aimed to synthesize scientific evidence of the mechanisms through which physical activity might reduce psychiatric symptoms across the lifespan. METHODS: We included articles that were published before March 2022 from five electronic databases (MEDLINE, Web of Science, PsycINFO, Embase, and Cochrane). A qualitative synthesis of studies was conducted. The risk of bias assessment was performed using The Joanna Briggs Institute Critical Appraisal Tool for Systematic Reviews. Studies were included if they explored the possible mechanisms through which physical activity influences psychiatric symptoms (i.e., internalizing and externalizing symptoms) across the lifespan. RESULTS: A total of 22 articles were included (three randomized controlled trials, four non-randomized controlled trials, three prospective longitudinal studies, and 12 cross-sectional studies). Overall, most of the studies focused on children, adolescents, and young adults. Our findings showed that self-esteem, self-concept, and self-efficacy were the only consistent paths through which physical activity influences psychiatric symptoms (specifically depressive and anxiety symptoms) across the lifespan. There were insufficient studies to determine the role of neurobiological mechanisms. CONCLUSIONS: Overall, future physical activity interventions with the purpose of improving mental health should consider these mechanisms (self-esteem, self-concept, self-efficacy) to develop more effective interventions. CLINICAL TRIAL REGISTRATION: The protocol of this study was registered in the PROSPERO database (registration number CRD42021239440) and published in April 2022.

Predicting amyloid-beta pathology in the general population.

INTRODUCTION: Reliable models to predict amyloid beta (Aß) positivity in the general aging population are lacking but could become cost-efficient tools to identify individuals at risk of developing Alzheimer's disease. METHODS: We developed Aß prediction models in the clinical Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) Study (n = 4,119) including a broad range of easily ascertainable predictors (demographics, cognition and daily functioning, health and lifestyle factors). Importantly, we determined the generalizability of our models in the population-based Rotterdam Study (n = 500). RESULTS: The best performing model in the A4 Study (area under the curve [AUC] = 0.73 [0.69-0.76]), including age, apolipoprotein E (APOE) ε4 genotype, family history of dementia, and subjective and objective measures of cognition, walking duration and sleep behavior, was validated in the independent Rotterdam Study with higher accuracy (AUC = 0.85 [0.81-0.89]). Yet, the improvement relative to a model including only age and APOE ε4 was marginal. DISCUSSION: Aß prediction models including inexpensive and non-invasive measures were successfully applied to a general population-derived sample more representative of typical older non-demented adults.

Mechanisms linking physical activity with psychiatric symptoms across the lifespan: a protocol for a systematic review.

INTRODUCTION: Persistent psychiatric symptomatology during childhood and adolescence predicts vulnerability to experience mental illness in adulthood. Physical activity is well-known to provide mental health benefits across the lifespan. However, the underlying mechanisms linking physical activity and psychiatric symptoms remain underexplored. In this context, we aim to systematically synthesise evidence focused on the mechanisms through which physical activity might reduce psychiatric symptoms across all ages. METHODS AND ANALYSIS: With the aid of a biomedical information specialist, we will develop a systematic search strategy based on the predetermined research question in the following electronic databases: MEDLINE, Embase, Web of Science, Cochrane and PsycINFO. Two independent reviewers will screen and select studies, extract data and assess the risk of bias. In case of inability to reach a consensus, a third person will be consulted. We will not apply any language restriction, and we will perform a qualitative synthesis of our findings as we anticipate that studies are scarce and heterogeneous. ETHICS AND DISSEMINATION: Only data that have already been published will be included. Then, ethical approval is not required. Findings will be published in a peer-reviewed journal and presented at conferences. Additionally, we will communicate our findings to healthcare providers and other sections of society (eg, through regular channels, including social media). PROSPERO REGISTRATION NUMBER: CRD42021239440.