{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T15:29:47Z","timestamp":1793892587233,"version":"4.8.0"},"reference-count":59,"publisher":"American Medical Association (AMA)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2024,8,1]]},"abstract":"\n Importance<\/jats:title>\n Sleep disturbances are common among older adults and have been associated with the development of Alzheimer disease (AD), such as amyloid-\u03b2 (A\u03b2) 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 A\u03b2 deposition.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To determine the associations of 24-hour activity rhythms and sleep with A\u03b2 deposition in adults without dementia, to evaluate whether disrupted 24-hour activity and sleep may precede A\u03b2 deposition, and to assess the role of the apolipoprotein E \u03b54 (\n APOE4<\/jats:italic>\n ) genotype.\n <\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n \n This was an observational cohort study using data from the Rotterdam Study. Of 639 participants without dementia who underwent A\u03b2 positron emission tomography (PET) from September 2018 to November 2021, 319 were included in the current study. Exclusion criteria were no\n APOE<\/jats:italic>\n 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.\n <\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n \n Actigraphy (7 days and nights, objective sleep, and 24-hour activity rhythms), sleep diaries (self-reported sleep), A\u03b242\/40, phosphorylated tau (p-tau)\n 181<\/jats:sub>\n and p-tau\n 217<\/jats:sub>\n plasma assays,\n 18<\/jats:sup>\n F-florbetaben PET (mean standard uptake value ratio [SUVR] in a large cortical region of interest), and\n APOE4<\/jats:italic>\n genotype.\n <\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Association of objective and self-reported sleep and 24-hour activity rhythms at baseline with brain A\u03b2 PET burden at follow-up.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n 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 A\u03b2 PET burden at follow-up (\u03b2, 0.15; bootstrapped 95% CI, 0.04 to 0.26; bootstrapped\n P<\/jats:italic>\n \u2009=\u2009.02, false discovery rate [FDR]\n P<\/jats:italic>\n \u2009=\u2009.048).\n APOE<\/jats:italic>\n genotype modified this association, which was stronger in\n APOE4<\/jats:italic>\n carriers (\u03b2, 0.38; bootstrapped 95% CI, 0.05 to 0.64; bootstrapped\n P<\/jats:italic>\n \u2009=\u2009.03) compared to noncarriers (\u03b2, 0.07; bootstrapped 95% CI, \u22120.04 to 0.18; bootstrapped\n P<\/jats:italic>\n \u2009=\u2009.19). The findings remained largely similar after excluding participants with AD pathology at baseline, suggesting that a fragmented 24-hour activity rhythm may have preceded A\u03b2 deposition. No other objective or self-reported measure of sleep was associated with A\u03b2.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n Among community-dwelling adults included in this study, higher fragmentation of the 24-hour activity rhythms was associated with greater subsequent A\u03b2 burden, especially in\n APOE4<\/jats:italic>\n carriers. These results suggest that rest-activity fragmentation could represent a modifiable risk factor for AD.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaneurol.2024.1755","type":"journal-article","created":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T11:00:41Z","timestamp":1719226841000},"page":"824","source":"Crossref","is-referenced-by-count":66,"title":["Sleep, 24-Hour Activity Rhythms, and Subsequent Amyloid-\u03b2 Pathology"],"prefix":"10.1001","volume":"81","author":[{"given":"Phuong Thuy","family":"Nguyen Ho","sequence":"first","affiliation":[{"name":"Department of Radiology and Nuclear Medicine, Erasmus University Medical Centre, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanne J. 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