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Circadian rhythm disturbances likely contribute to dementia pathogenesis, but whether these disturbances are related to delirium risk and progression to all\u2010cause dementia is unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed continuous actigraphy data from 53,417 middle\u2010aged or older UK Biobank participants during a median 5\u2009years of follow\u2010up. Four measures were used to characterize the 24\u2010hour daily rest\u2013activity rhythms (RARs): normalized amplitude, acrophase representing the peak activity time, interdaily stability, and intradaily variability (IV) for fragmentation of the rhythm. Cox proportional hazards models examined whether RARs predicted incident delirium (n\u00a0=\u00a0551) and progression to dementia (n\u00a0=\u00a061).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Suppressed 24\u2010hour amplitude, lowest (Q1) versus highest (Q4) quartile (hazard ratio [HR]<jats:sub>Q1 vs Q4<\/jats:sub>=\u20091.94, 95% confidence interval [CI] =\u20091.53\u20132.46,<jats:italic>p<\/jats:italic>\u00a0&lt;\u20090.001), and more fragmented (higher IV: HR<jats:sub>Q4 vs Q1<\/jats:sub>=\u20091.49, 95% CI\u00a0=\u00a01.18\u20131.88,<jats:italic>p<\/jats:italic>\u00a0&lt;\u20090.001) rhythms predicted higher delirium risk, after adjusting for age, sex, education, cognitive performance, sleep duration\/disturbances, and comorbidities. In those free from dementia, each hour of delayed acrophase was associated with delirium risk (HR =\u20091.13, 95% CI\u00a0=\u00a01.04\u20131.23,<jats:italic>p<\/jats:italic>\u00a0=\u20090.003). Suppressed 24\u2010hour amplitude was associated with increased risk of progression from delirium to new onset dementia (HR\u00a0=\u00a01.31, 95% CI\u00a0=\u00a01.03\u20131.67,<jats:italic>p<\/jats:italic>\u00a0=\u20090.03 for each 1\u2010standard deviation decrease).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Twenty\u2010four\u2010hour daily RAR suppression, fragmentation, and potentially delayed acrophase were associated with delirium risk. Subsequent progression to dementia was more likely in delirium cases with suppressed rhythms. The presence of RAR disturbances before delirium and prior to progression to dementia suggests that these disturbances may predict higher risk and be involved in early disease pathogenesis. ANN NEUROL 2023;93:1145\u20131157<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.26617","type":"journal-article","created":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T02:04:36Z","timestamp":1676945076000},"page":"1145-1157","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Circadian Rest\u2013Activity Rhythms, Delirium Risk, and Progression to Dementia"],"prefix":"10.1002","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1476-1460","authenticated-orcid":false,"given":"Lei","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital Harvard Medical School Boston MA USA"},{"name":"Medical Biodynamics Program, Division of Sleep and Circadian Disorders Brigham and Women's Hospital Boston MA USA"},{"name":"Division of Sleep Medicine Harvard Medical School Boston MA USA"},{"name":"Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Li","sequence":"additional","affiliation":[{"name":"Medical Biodynamics Program, Division of Sleep and Circadian Disorders Brigham and Women's Hospital Boston MA USA"},{"name":"Division of Sleep Medicine Harvard Medical School Boston MA USA"},{"name":"Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Gaykova","sequence":"additional","affiliation":[{"name":"Medical Biodynamics Program, Division of Sleep and Circadian Disorders Brigham and Women's Hospital Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Medical Biodynamics Program, Division of Sleep and Circadian Disorders Brigham and Women's Hospital Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenlu","family":"Gao","sequence":"additional","affiliation":[{"name":"Medical Biodynamics Program, Division of Sleep and Circadian Disorders Brigham and Women's Hospital Boston MA USA"},{"name":"Division of Sleep Medicine Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline M.","family":"Lane","sequence":"additional","affiliation":[{"name":"Division of Sleep Medicine Harvard Medical School Boston MA USA"},{"name":"Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge MA USA"},{"name":"Center for Genomic Medicine Massachusetts General Hospital Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richa","family":"Saxena","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital Harvard Medical School Boston MA USA"},{"name":"Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge MA USA"},{"name":"Center for Genomic Medicine Massachusetts General Hospital Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank A. 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