The bidirectional relationship between brain structure and physical activity: A longitudinal analysis in the UK Biobank.

Physical activity is a protective factor against brain atrophy, while loss of brain volume could also be a determinant of physical activity. Therefore, we aimed to explore the bidirectional association of physical activity with brain structures in middle-aged and older adults from the UK Biobank. Overall, 3027 participants (62.45 ± 7.27 years old, 51.3% females) had data at two time points. Hippocampal volume was associated with total (ß=0.048, pFDR=0.016) and household (ß=0.075, pFDR<0.001) physical activity. Global fractional anisotropy (ß=0.042, pFDR=0.028) was also associated with household physical activity. In the opposite direction, walking was negatively associated with white matter volume (ß=-0.026, pFDR=0.008). All these associations were confirmed by the linear mixed models. Interestingly, sports at baseline were linked to hippocampal and frontal cortex volumes at follow-up but these associations disappeared after adjusting for multiple comparisons (pall>0.104). In conclusion, we found more consistent evidence that a healthier brain structure predicted higher physical activity levels than for the inverse, more established relationship.

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.