{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T15:36:40Z","timestamp":1792683400592,"version":"4.5.0"},"reference-count":105,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"vor","delay-in-days":250,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["PA-21-071"],"award-info":[{"award-number":["PA-21-071"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100023864","name":"NIA","doi-asserted-by":"publisher","award":["R01AG065356"],"award-info":[{"award-number":["R01AG065356"]}],"id":[{"id":"10.13039\/501100023864","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG046928"],"award-info":[{"award-number":["R01AG046928"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Several studies implicate circadian rhythm disturbances in Alzheimer\u2019s disease. However, very little is known about how circadian rhythms are associated with Alzheimer\u2019s pathological biomarkers in older adults at early stages of the disease, and how these relationships map onto cognition. This cross-sectional study used 24-h accelerometry data to investigate the relationships between circadian rhythms, amyloid-\u03b2 (A\u03b2), tau, and cognition in 68 older adults with objective early cognitive impairment. Participants wore GENEActiv accelerometers for \u223c1 month (mean = 31.8 days). Circadian rhythms measures were quantified from accelerometer data and included acrotime (average time of day of peak activity) and intradaily variability (IV) (average circadian rhythm fragmentation within a day). A\u03b2 was measured as a composite, and tau (n = 67) was measured in Braak staging regions of interest I\/II and III\/IV using positron emission tomography. The cognitive domains used were verbal memory (California Verbal Learning Test short delay free recall) and attention\/processing speed (Digit Symbol Substitution Test). Multivariable linear regression models were conducted to test for associations between circadian rhythms and the outcome variables of A\u03b2, tau, and cognition. The moderating effects of age, sex, and apolipoprotein E4 (APOE4) carrier status were assessed in these associations. To investigate mechanistic pathways through which circadian rhythms may impact cognition, exploratory mediation analyses were conducted post hoc. Models were adjusted for age, sex, APOE4 carrier status, and years of education. The study included 68 older adults (mean age = 66.8 years, age range = 55\u201380 years, 63.2% female, 26.5% APOE4 carriers). Earlier acrotime was associated with higher A\u03b2 and tau, the former of which was stronger in APOE4 carriers relative to non-carriers. Higher IV was related to higher tau in Braak regions III\/IV. Age and sex modified the association between IV and tau, in which the relationships strengthened with increasing age and disproportionately affected men. Earlier acrotime was associated with worse verbal memory, but later acrotime was associated with worse attention\/processing speed. Tau in Braak regions I\u2013IV mediated the relationship between acrotime and verbal memory. The insights from this study revealed that circadian rhythms were associated with A\u03b2, tau, and cognition in older adults with objective early cognitive impairment. We provide novel evidence for tau as a biological mediator in the relationship between circadian timing and cognition. This work identified circadian rhythms as a promising point of intervention to reduce Alzheimer\u2019s disease risk and potentially mitigate pathological progression and cognitive decline.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf322","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T19:01:07Z","timestamp":1757358067000},"source":"Crossref","is-referenced-by-count":11,"title":["Circadian rhythms are associated with higher amyloid-\u03b2 and tau and poorer cognition in older adults"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0087-7967","authenticated-orcid":false,"given":"Joanna L","family":"Eckhardt","sequence":"first","affiliation":[{"name":"Alzheimer\u2019s Disease Cooperative Study (ADCS), Department of Neurosciences, University of California, San Diego , La Jolla, CA 92093 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisette","family":"Isenberg","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease Cooperative Study (ADCS), Department of Neurosciences, University of California, San Diego , La Jolla, CA 92093 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vahan","family":"Aslanyan","sequence":"additional","affiliation":[{"name":"Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California , Los Angeles, CA 90007 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Monreal","sequence":"additional","affiliation":[{"name":"Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California , Los Angeles, CA 90007 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joy","family":"Stradford","sequence":"additional","affiliation":[{"name":"SDSU\/UCSD Joint Doctoral Program in Clinical Psychology, University of California, San Diego , La Jolla, CA 92093 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5234-3927","authenticated-orcid":false,"given":"Laura","family":"Fenton","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Southern California , Los Angeles, CA 90007 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joey A","family":"Contreras","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease Cooperative Study (ADCS), Department of Neurosciences, University of California, San Diego , La Jolla, CA 92093 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy J","family":"Mack","sequence":"additional","affiliation":[{"name":"Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California , Los Angeles, CA 90007 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy","family":"Pa","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease Cooperative Study (ADCS), Department of Neurosciences, University of California, San Diego , La Jolla, CA 92093 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,9,8]]},"reference":[{"issue":"Pt 3","key":"2025090913321940100_fcaf322-B1","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/j.1469-7793.2000.00695.x","article-title":"Sensitivity of the human circadian pacemaker to nocturnal light: Melatonin phase resetting and suppression","volume":"526","author":"Zeitzer","year":"2000","journal-title":"J Physiol"},{"issue":"1","key":"2025090913321940100_fcaf322-B2","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0166-4328(00)00236-9","article-title":"Dose-response relationship for light intensity and ocular and electroencephalographic correlates of human alertness","volume":"115","author":"Cajochen","year":"2000","journal-title":"Behav Brain Res"},{"key":"2025090913321940100_fcaf322-B3","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.coemr.2021.03.011","article-title":"Sleep and circadian regulation of cortisol: A short review","volume":"18","author":"O\u2019Byrne","year":"2021","journal-title":"Curr Opin Endocr Metab Res"},{"issue":"1","key":"2025090913321940100_fcaf322-B4","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/0006-8993(90)90214-V","article-title":"Daily variation in the concentration of melatonin and 5-methoxytryptophol in the human pineal gland: Effect of age and Alzheimer\u2019s disease","volume":"528","author":"Skene","year":"1990","journal-title":"Brain Res"},{"issue":"1","key":"2025090913321940100_fcaf322-B5","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/0006-8993(96)00086-8","article-title":"Daily rhythm of serum melatonin in patients with dementia of the degenerate type","volume":"717","author":"Uchida","year":"1996","journal-title":"Brain Res"},{"issue":"1","key":"2025090913321940100_fcaf322-B6","first-page":"323","article-title":"Decreased melatonin levels in postmortem cerebrospinal fluid in relation to aging, Alzheimer\u2019s disease, and apolipoprotein E-\u03b54\/4 genotype","volume":"84","author":"Liu","year":"1999","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2025090913321940100_fcaf322-B7","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S0006-3223(97)00510-6","article-title":"Melatonin secretion rhythm disorders in patients with senile dementia of Alzheimer\u2019s type with disturbed sleep\u2013waking","volume":"45","author":"Mishima","year":"1999","journal-title":"Biol Psychiatry"},{"issue":"12","key":"2025090913321940100_fcaf322-B8","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1016\/S0006-3223(98)00255-8","article-title":"Daily rhythm of serum melatonin levels and effect of light exposure in patients with dementia of the Alzheimer\u2019s type","volume":"45","author":"Ohashi","year":"1999","journal-title":"Biol Psychiatry"},{"issue":"2","key":"2025090913321940100_fcaf322-B9","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1034\/j.1600-079X.2003.00065.x","article-title":"Early neuropathological Alzheimer\u2019s changes in aged individuals are accompanied by decreased cerebrospinal fluid melatonin levels","volume":"35","author":"Zhou","year":"2003","journal-title":"J Pineal Res"},{"issue":"8","key":"2025090913321940100_fcaf322-B10","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1016\/j.neurobiolaging.2006.06.002","article-title":"Decreased MT1 melatonin receptor expression in the suprachiasmatic nucleus in aging and Alzheimer\u2019s disease","volume":"28","author":"Wu","year":"2007","journal-title":"Neurobiol Aging"},{"key":"2025090913321940100_fcaf322-B11","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3389\/fnagi.2019.00043","article-title":"High cortisol and the risk of dementia and Alzheimer\u2019s disease: A review of the literature","volume":"11","author":"Ouanes","year":"2019","journal-title":"Front Aging Neurosci"},{"issue":"6","key":"2025090913321940100_fcaf322-B12","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/0006-3223(90)90523-5","article-title":"Alterations in the circadian rest-activity rhythm in aging and Alzheimer\u2019s disease","volume":"27","author":"Witting","year":"1990","journal-title":"Biol Psychiatry"},{"issue":"5","key":"2025090913321940100_fcaf322-B13","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/0197-4580(95)00059-N","article-title":"Circadian locomotor activity and core-body temperature rhythms in Alzheimer\u2019s disease","volume":"16","author":"Satlin","year":"1995","journal-title":"Neurobiol Aging"},{"issue":"5","key":"2025090913321940100_fcaf322-B14","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1093\/brain\/awh129","article-title":"Disrupted daily activity\/rest cycles in relation to daily cortisol rhythms of home-dwelling patients with early Alzheimer\u2019s dementia","volume":"127","author":"Hatfield","year":"2004","journal-title":"Brain"},{"issue":"1","key":"2025090913321940100_fcaf322-B15","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1097\/WAD.0000000000000037","article-title":"The rest-activity rhythm and physical activity in early-onset dementia","volume":"29","author":"Hooghiemstra","year":"2015","journal-title":"Alzheimer Dis Assoc Disord"},{"issue":"4","key":"2025090913321940100_fcaf322-B16","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/0006-3223(95)00370-3","article-title":"Circadian rest\u2014Activity rhythm disturbances in Alzheimer\u2019s disease","volume":"40","author":"van Someren","year":"1996","journal-title":"Biol Psychiatry"},{"issue":"5","key":"2025090913321940100_fcaf322-B17","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1176\/appi.ajp.158.5.704","article-title":"Sundowning and circadian rhythms in Alzheimer\u2019s disease","volume":"158","author":"Volicer","year":"2001","journal-title":"Am J Psychiatry"},{"issue":"1","key":"2025090913321940100_fcaf322-B18","first-page":"18","article-title":"Variations in circadian rhythms of activity, sleep, and light exposure related to dementia in nursing-home patients","volume":"20","author":"Ancoli-Israel","year":"1997","journal-title":"Sleep"},{"issue":"4","key":"2025090913321940100_fcaf322-B19","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1001\/archpsyc.58.4.353","article-title":"Differential circadian rhythm disturbances in men with Alzheimer disease and frontotemporal degeneration","volume":"58","author":"Harper","year":"2001","journal-title":"Arch Gen Psychiatry"},{"issue":"6","key":"2025090913321940100_fcaf322-B20","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1093\/sleep\/14.6.478","article-title":"Circadian rhythm disorders in sleep-waking and body temperature in elderly patients with dementia and their treatment","volume":"14","author":"Okawa","year":"1991","journal-title":"Sleep"},{"issue":"5","key":"2025090913321940100_fcaf322-B21","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1097\/00019442-200505000-00004","article-title":"Disturbance of endogenous circadian rhythm in aging and Alzheimer disease","volume":"13","author":"Harper","year":"2005","journal-title":"Am J Geriatr Psychiatry"},{"issue":"3","key":"2025090913321940100_fcaf322-B22","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/0165-1781(93)90078-U","article-title":"Sleep and \u201csundowning\u201d in nursing home patients with dementia","volume":"48","author":"Bliwise","year":"1993","journal-title":"Psychiatry Res"},{"issue":"1","key":"2025090913321940100_fcaf322-B23","first-page":"524971","article-title":"The characterization of biological rhythms in mild cognitive impairment","volume":"2014","author":"Ortiz-Tudela","year":"2014","journal-title":"BioMed Res Int"},{"issue":"11","key":"2025090913321940100_fcaf322-B24","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1111\/jgs.15555","article-title":"Rest-activity rhythms and cognitive decline in older men: The osteoporotic fractures in men sleep study","volume":"66","author":"Rogers-Soeder","year":"2018","journal-title":"J Am Geriatr Soc"},{"issue":"5","key":"2025090913321940100_fcaf322-B25","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1001\/jamaneurol.2017.4719","article-title":"Circadian rest-activity pattern changes in aging and preclinical Alzheimer disease","volume":"75","author":"Musiek","year":"2018","journal-title":"JAMA Neurol"},{"key":"2025090913321940100_fcaf322-B26","doi-asserted-by":"crossref","first-page":"100065","DOI":"10.1016\/j.nbscr.2021.100065","article-title":"A population-based prospective study on rest-activity rhythm and mild cognitive impairment among Hong Kong healthy community-dwelling older adults","volume":"10","author":"Yi Lee","year":"2021","journal-title":"Neurobiol Sleep Circadian Rhythms"},{"issue":"1","key":"2025090913321940100_fcaf322-B27","doi-asserted-by":"crossref","DOI":"10.1093\/sleepadvances\/zpab007","article-title":"Associations of actigraphic sleep and circadian rest\/activity rhythms with cognition in the early phase of Alzheimer\u2019s disease","volume":"2","author":"Alfini","year":"2021","journal-title":"SLEEP Adv"},{"issue":"10","key":"2025090913321940100_fcaf322-B28","doi-asserted-by":"crossref","first-page":"2925","DOI":"10.1111\/jgs.17926","article-title":"Rest-activity rhythms and cognitive impairment and dementia in older women: Results from the women\u2019s health initiative","volume":"70","author":"Xiao","year":"2022","journal-title":"J Am Geriatr Soc"},{"issue":"1","key":"2025090913321940100_fcaf322-B29","doi-asserted-by":"crossref","first-page":"4","DOI":"10.5334\/jcr.227","article-title":"Abnormalities of rest-activity and light exposure rhythms associated with cognitive function in patients with mild cognitive impairment (MCI)","volume":"21","author":"Kim","year":"2023","journal-title":"J Circadian Rhythms"},{"issue":"5","key":"2025090913321940100_fcaf322-B30","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1002\/ana.22468","article-title":"Circadian activity rhythms and risk of incident dementia and mild cognitive impairment in older women","volume":"70","author":"Tranah","year":"2011","journal-title":"Ann Neurol"},{"key":"2025090913321940100_fcaf322-B31","author":"The R Foundation"},{"key":"2025090913321940100_fcaf322-B32","author":"ActivInsights"},{"key":"2025090913321940100_fcaf322-B33","author":"van Hees"},{"issue":"3","key":"2025090913321940100_fcaf322-B34","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1123\/jmpb.2018-0063","article-title":"GGIR: A research community\u2013driven open source R package for generating physical activity and sleep outcomes from multi-day raw accelerometer data","volume":"2","author":"Migueles","year":"2019","journal-title":"J Meas Phys Behav"},{"issue":"4","key":"2025090913321940100_fcaf322-B35","doi-asserted-by":"crossref","first-page":"e61691","DOI":"10.1371\/journal.pone.0061691","article-title":"Separating movement and gravity components in an acceleration signal and implications for the assessment of human daily physical activity","volume":"8","author":"van Hees","year":"2013","journal-title":"PLoS One"},{"issue":"2","key":"2025090913321940100_fcaf322-B36","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1080\/00140138008924730","article-title":"Spring and autumn daylight saving time changes: Studies of adjustment in sleep timings, mood, and efficiency","volume":"23","author":"Monk","year":"1980","journal-title":"Ergonomics"},{"issue":"3","key":"2025090913321940100_fcaf322-B37","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1093\/sleep\/26.3.342","article-title":"The role of actigraphy in the study of sleep and circadian rhythms","volume":"26","author":"Ancoli-Israel","year":"2003","journal-title":"Sleep"},{"issue":"1","key":"2025090913321940100_fcaf322-B38","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/1742-4682-11-16","article-title":"Cosinor-based rhythmometry","volume":"11","author":"Cornelissen","year":"2014","journal-title":"Theor Biol Med Model"},{"issue":"3","key":"2025090913321940100_fcaf322-B39","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1081\/CBI-100101054","article-title":"Circadian rhythms of agitation in institutionalized patients with Alzheimer\u2019s disease","volume":"17","author":"Martin","year":"2000","journal-title":"Chronobiol Int"},{"issue":"8","key":"2025090913321940100_fcaf322-B40","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1080\/09291016.2021.1929673","article-title":"Registration of 24-hour accelerometric rest-activity profiles and its application to human chronotypes","volume":"53","author":"McDonnell","year":"2022","journal-title":"Biol Rhythm Res"},{"key":"2025090913321940100_fcaf322-B41","author":"Di"},{"issue":"2","key":"2025090913321940100_fcaf322-B42","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1007\/s12561-019-09236-4","article-title":"Joint and individual representation of domains of physical activity, sleep, and circadian rhythmicity","volume":"11","author":"Di","year":"2019","journal-title":"Stat Biosci"},{"key":"2025090913321940100_fcaf322-B43","author":"Schabus"},{"key":"2025090913321940100_fcaf322-B44","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.mex.2016.05.006","article-title":"nparACT\u2019 package for R: A free software tool for the non-parametric analysis of actigraphy data","volume":"3","author":"Blume","year":"2016","journal-title":"MethodsX"},{"issue":"4","key":"2025090913321940100_fcaf322-B45","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/S0031-9384(02)00733-3","article-title":"Age-associated difference in circadian sleep\u2013wake and rest\u2013activity rhythms","volume":"76","author":"Huang","year":"2002","journal-title":"Physiol Behav"},{"issue":"9","key":"2025090913321940100_fcaf322-B46","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/S0006-3223(97)89928-3","article-title":"Indirect bright light improves circadian rest-activity rhythm disturbances in demented patients","volume":"41","author":"Someren","year":"1997","journal-title":"Biol Psychiatry"},{"issue":"4","key":"2025090913321940100_fcaf322-B47","doi-asserted-by":"crossref","first-page":"505","DOI":"10.3109\/07420529908998724","article-title":"Bright light therapy: Improved sensitivity to its effects on rest-activity rhythms in Alzheimer patients by application of nonparametric methods","volume":"16","author":"Van Someren","year":"1999","journal-title":"Chronobiol Int"},{"issue":"1","key":"2025090913321940100_fcaf322-B48","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0166-4328(98)00150-8","article-title":"Transcutaneous electrical nerve stimulation (TENS) improves the rest\u2013activity rhythm in midstage Alzheimer\u2019s disease","volume":"101","author":"Scherder","year":"1999","journal-title":"Behav Brain Res"},{"key":"2025090913321940100_fcaf322-B49","author":"Thoen"},{"issue":"2","key":"2025090913321940100_fcaf322-B50","doi-asserted-by":"crossref","first-page":"fcad031","DOI":"10.1093\/braincomms\/fcad031","article-title":"Variability in objective sleep is associated with Alzheimer\u2019s pathology and cognition","volume":"5","author":"Fenton","year":"2023","journal-title":"Brain Commun"},{"issue":"44","key":"2025090913321940100_fcaf322-B51","doi-asserted-by":"crossref","first-page":"8573","DOI":"10.1523\/JNEUROSCI.1230-20.2020","article-title":"Associations between vascular function and tau PET are associated with global cognition and amyloid","volume":"40","author":"Albrecht","year":"2020","journal-title":"J Neurosci"},{"key":"2025090913321940100_fcaf322-B52","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.bbi.2021.01.010","article-title":"Early neuroinflammation is associated with lower amyloid and tau levels in cognitively normal older adults","volume":"94","author":"Albrecht","year":"2021","journal-title":"Brain Behav Immun"},{"issue":"3","key":"2025090913321940100_fcaf322-B53","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1016\/j.neuroimage.2009.09.062","article-title":"The optimal template effect in hippocampus studies of diseased populations","volume":"49","author":"Avants","year":"2010","journal-title":"NeuroImage"},{"issue":"3","key":"2025090913321940100_fcaf322-B54","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1016\/j.neuroimage.2010.09.025","article-title":"A reproducible evaluation of ANTs similarity metric performance in brain image registration","volume":"54","author":"Avants","year":"2011","journal-title":"NeuroImage"},{"key":"2025090913321940100_fcaf322-B55","author":"Laboratories for Computational Neuroimaging"},{"key":"2025090913321940100_fcaf322-B56","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1016\/j.dib.2017.10.024","article-title":"Considerations and code for partial volume correcting [18F]-AV-1451 tau PET data","volume":"15","author":"Baker","year":"2017","journal-title":"Data Brief"},{"issue":"1","key":"2025090913321940100_fcaf322-B57","first-page":"21","article-title":"Tau-PET uptake: Regional variation in average SUVR and impact of amyloid deposition","volume":"6","author":"Vemuri","year":"2017","journal-title":"Alzheimers Dement Diagn Assess Dis Monit"},{"issue":"1","key":"2025090913321940100_fcaf322-B58","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.neuroimage.2006.05.056","article-title":"A spatially unbiased atlas template of the human cerebellum","volume":"33","author":"Diedrichsen","year":"2006","journal-title":"NeuroImage"},{"issue":"1","key":"2025090913321940100_fcaf322-B59","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.neuroimage.2009.01.045","article-title":"A probabilistic MR atlas of the human cerebellum","volume":"46","author":"Diedrichsen","year":"2009","journal-title":"NeuroImage"},{"issue":"3","key":"2025090913321940100_fcaf322-B60","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1016\/j.neuroimage.2010.10.035","article-title":"Imaging the deep cerebellar nuclei: A probabilistic atlas and normalization procedure","volume":"54","author":"Diedrichsen","year":"2011","journal-title":"NeuroImage"},{"issue":"7","key":"2025090913321940100_fcaf322-B61","doi-asserted-by":"crossref","first-page":"e0133402","DOI":"10.1371\/journal.pone.0133402","article-title":"Surface-based display of volume-averaged cerebellar imaging data","volume":"10","author":"Diedrichsen","year":"2015","journal-title":"PLoS One"},{"key":"2025090913321940100_fcaf322-B62","author":"Landau"},{"issue":"4","key":"2025090913321940100_fcaf322-B63","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/BF00308809","article-title":"Neuropathological stageing of Alzheimer-related changes","volume":"82","author":"Braak","year":"1991","journal-title":"Acta Neuropathol."},{"issue":"5","key":"2025090913321940100_fcaf322-B64","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/j.neuron.2016.01.028","article-title":"PET imaging of tau deposition in the aging human brain","volume":"89","author":"Sch\u00f6ll","year":"2016","journal-title":"Neuron"},{"issue":"5","key":"2025090913321940100_fcaf322-B65","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.acn.2006.06.002","article-title":"The California verbal learning test\u2014Second edition: Test-retest reliability, practice effects, and reliable change indices for the standard and alternate forms","volume":"21","author":"Woods","year":"2006","journal-title":"Arch Clin Neuropsychol"},{"issue":"5","key":"2025090913321940100_fcaf322-B66","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1097\/JCP.0000000000000941","article-title":"Digit symbol substitution test: The case for sensitivity over specificity in neuropsychological testing","volume":"38","author":"Jaeger","year":"2018","journal-title":"J Clin Psychopharmacol"},{"key":"2025090913321940100_fcaf322-B67","author":"Tingley"},{"issue":"5","key":"2025090913321940100_fcaf322-B68","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1001\/jamaneurol.2013.2334","article-title":"Sleep quality and preclinical Alzheimer disease","volume":"70","author":"Ju","year":"2013","journal-title":"JAMA Neurol"},{"issue":"1","key":"2025090913321940100_fcaf322-B69","doi-asserted-by":"crossref","first-page":"zpab015","DOI":"10.1093\/sleepadvances\/zpab015","article-title":"Brain amyloid burden, sleep, and 24-hour rest\/activity rhythms: Screening findings from the anti-amyloid treatment in asymptomatic Alzheimer\u2019s and longitudinal evaluation of amyloid risk and neurodegeneration studies","volume":"2","author":"Spira","year":"2021","journal-title":"SLEEP Adv"},{"issue":"4","key":"2025090913321940100_fcaf322-B70","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1111\/pcn.13521","article-title":"Circadian rest-activity rhythm and longitudinal brain changes underlying late-life cognitive decline","volume":"77","author":"Jeon","year":"2023","journal-title":"Psychiatry Clin Neurosci"},{"issue":"4","key":"2025090913321940100_fcaf322-B71","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.jsmc.2015.08.002","article-title":"Aging and circadian rhythms","volume":"10","author":"Duffy","year":"2015","journal-title":"Sleep Med Clin"},{"issue":"1","key":"2025090913321940100_fcaf322-B72","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1073\/pnas.1508249112","article-title":"Effects of aging on circadian patterns of gene expression in the human prefrontal cortex","volume":"113","author":"Chen","year":"2016","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"10","key":"2025090913321940100_fcaf322-B73","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.3109\/07420528.2013.813528","article-title":"Stability and fragmentation of the activity rhythm across the sleep-wake cycle: The importance of age, lifestyle, and mental health","volume":"30","author":"Luik","year":"2013","journal-title":"Chronobiol Int"},{"issue":"1","key":"2025090913321940100_fcaf322-B74","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/s12966-021-01174-z","article-title":"Demographic characteristics associated with circadian rest-activity rhythm patterns: A cross-sectional study","volume":"18","author":"Li","year":"2021","journal-title":"Int J Behav Nutr Phys Act"},{"issue":"4","key":"2025090913321940100_fcaf322-B75","doi-asserted-by":"crossref","first-page":"857","DOI":"10.3233\/JAD-131217","article-title":"Circadian misalignment and sleep disruption in mild cognitive impairment","volume":"38","author":"Naismith","year":"2014","journal-title":"J Alzheimers Dis."},{"issue":"3","key":"2025090913321940100_fcaf322-B76","doi-asserted-by":"crossref","first-page":"e96","DOI":"10.1016\/S2666-7568(20)30015-5","article-title":"Circadian disturbances in Alzheimer\u2019s disease progression: A prospective observational cohort study of community-based older adults","volume":"1","author":"Li","year":"2020","journal-title":"Lancet Healthy Longev"},{"issue":"5955","key":"2025090913321940100_fcaf322-B77","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1126\/science.1180962","article-title":"Amyloid-\u03b2 dynamics are regulated by orexin and the sleep-wake cycle","volume":"326","author":"Kang","year":"2009","journal-title":"Science"},{"issue":"4","key":"2025090913321940100_fcaf322-B78","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1084\/jem.20172347","article-title":"Regulation of amyloid-\u03b2 dynamics and pathology by the circadian clock","volume":"215","author":"Kress","year":"2018","journal-title":"J Exp Med"},{"issue":"6156","key":"2025090913321940100_fcaf322-B79","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1126\/science.1241224","article-title":"Sleep drives metabolite clearance from the adult brain","volume":"342","author":"Xie","year":"2013","journal-title":"Science"},{"issue":"1","key":"2025090913321940100_fcaf322-B80","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1001\/archneurol.2011.235","article-title":"Effects of age and amyloid deposition on A\u03b2 dynamics in the human central nervous system","volume":"69","author":"Huang","year":"2012","journal-title":"Arch Neurol"},{"issue":"2","key":"2025090913321940100_fcaf322-B81","doi-asserted-by":"crossref","first-page":"e1009994","DOI":"10.1371\/journal.pgen.1009994","article-title":"Circadian control of heparan sulfate levels times phagocytosis of amyloid beta aggregates","volume":"18","author":"Clark","year":"2022","journal-title":"PLOS Genet"},{"issue":"3","key":"2025090913321940100_fcaf322-B82","doi-asserted-by":"crossref","first-page":"e148","DOI":"10.1038\/emm.2014.121","article-title":"Sleep, circadian rhythms, and the pathogenesis of Alzheimer disease","volume":"47","author":"Musiek","year":"2015","journal-title":"Exp Mol Med"},{"issue":"1","key":"2025090913321940100_fcaf322-B83","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1177\/0891988703261994","article-title":"Sleep\/wake disruption in Alzheimer\u2019s disease: APOE status and longitudinal course","volume":"17","author":"Yesavage","year":"2004","journal-title":"J Geriatr Psychiatry Neurol"},{"issue":"1","key":"2025090913321940100_fcaf322-B84","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s13195-022-00992-y","article-title":"APOE \u03b54, Alzheimer\u2019s disease neuropathology and sleep disturbance, in individuals with and without dementia","volume":"14","author":"Blackman","year":"2022","journal-title":"Alzheimers Res Ther"},{"issue":"6","key":"2025090913321940100_fcaf322-B85","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1002\/1531-8249(200006)47:6<739::AID-ANA6>3.0.CO;2-8","article-title":"Apolipoprotein E facilitates neuritic and cerebrovascular plaque formation in an Alzheimer\u2019s disease model","volume":"47","author":"Holtzman","year":"2000","journal-title":"Ann Neurol"},{"issue":"3","key":"2025090913321940100_fcaf322-B86","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1006\/nbdi.2002.0483","article-title":"Human and murine ApoE markedly alters A\u03b2 metabolism before and after plaque formation in a mouse model of Alzheimer\u2019s disease","volume":"9","author":"Fagan","year":"2002","journal-title":"Neurobiol Dis"},{"issue":"49","key":"2025090913321940100_fcaf322-B87","doi-asserted-by":"crossref","first-page":"18007","DOI":"10.1523\/JNEUROSCI.3773-11.2011","article-title":"Haploinsufficiency of human APOE reduces amyloid deposition in a mouse model of amyloid-\u03b2 amyloidosis","volume":"31","author":"Kim","year":"2011","journal-title":"J Neurosci"},{"issue":"6","key":"2025090913321940100_fcaf322-B88","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1002\/ana.21696","article-title":"Apolipoprotein E\u2013dependent accumulation of Alzheimer disease\u2013related lesions begins in middle age","volume":"65","author":"Kok","year":"2009","journal-title":"Ann Neurol"},{"issue":"3","key":"2025090913321940100_fcaf322-B89","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1212\/WNL.42.3.631","article-title":"Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer\u2019s disease","volume":"42","author":"Arriagada","year":"1992","journal-title":"Neurology"},{"issue":"11","key":"2025090913321940100_fcaf322-B90","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1038\/s41591-022-02049-x","article-title":"Amyloid and tau PET-positive cognitively unimpaired individuals are at high risk for future cognitive decline","volume":"28","author":"Ossenkoppele","year":"2022","journal-title":"Nat Med"},{"issue":"10","key":"2025090913321940100_fcaf322-B91","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1001\/jamaneurol.2022.2379","article-title":"Association of elevated amyloid and tau positron emission tomography signal with near-term development of Alzheimer disease symptoms in older adults without cognitive impairment","volume":"79","author":"Strikwerda-Brown","year":"2022","journal-title":"JAMA Neurol"},{"issue":"8","key":"2025090913321940100_fcaf322-B92","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.2967\/jnumed.122.265200","article-title":"The use of tau PET to stage Alzheimer disease according to the Braak staging framework","volume":"64","author":"Macedo","year":"2023","journal-title":"J Nucl Med"},{"issue":"4","key":"2025090913321940100_fcaf322-B93","doi-asserted-by":"crossref","first-page":"zsz266","DOI":"10.1093\/sleep\/zsz266","article-title":"Circadian and sleep\/wake-dependent variations in tau phosphorylation are driven by temperature","volume":"43","author":"Guisle","year":"2020","journal-title":"Sleep"},{"issue":"8","key":"2025090913321940100_fcaf322-B94","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1016\/j.neurobiolaging.2014.02.011","article-title":"Sleep deprivation impairs memory, tau metabolism, and synaptic integrity of a mouse model of Alzheimer\u2019s disease with plaques and tangles","volume":"35","author":"Di Meco","year":"2014","journal-title":"Neurobiol Aging"},{"issue":"3","key":"2025090913321940100_fcaf322-B95","doi-asserted-by":"crossref","first-page":"196","DOI":"10.5607\/en22019","article-title":"The change in circadian rhythms in P301S transgenic mice is linked to variability in Hsp70-related tau disaggregation","volume":"31","author":"Han","year":"2022","journal-title":"Exp Neurobiol"},{"issue":"1","key":"2025090913321940100_fcaf322-B96","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1111\/jphp.12830","article-title":"Melatonin ameliorates A\u03b21-42-induced Alzheimer\u2019s cognitive deficits in mouse model","volume":"70","author":"Gong","year":"2018","journal-title":"J Pharm Pharmacol"},{"key":"2025090913321940100_fcaf322-B97","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.expneurol.2017.04.015","article-title":"Disruption of normal circadian clock function in a mouse model of tauopathy","volume":"294","author":"Stevanovic","year":"2017","journal-title":"Exp Neurol"},{"issue":"7","key":"2025090913321940100_fcaf322-B98","doi-asserted-by":"crossref","first-page":"14575","DOI":"10.3390\/ijms140714575","article-title":"Melatonin in Alzheimer\u2019s disease","volume":"14","author":"Lin","year":"2013","journal-title":"Int J Mol Sci"},{"issue":"4","key":"2025090913321940100_fcaf322-B99","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1177\/0748730410374943","article-title":"Sex differences in phase angle of entrainment and melatonin amplitude in humans","volume":"25","author":"Cain","year":"2010","journal-title":"J Biol Rhythms"},{"issue":"12","key":"2025090913321940100_fcaf322-B100","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.5665\/sleep.4260","article-title":"Weaker circadian activity rhythms are associated with poorer executive function in older women","volume":"37","author":"Walsh","year":"2014","journal-title":"Sleep"},{"issue":"7","key":"2025090913321940100_fcaf322-B101","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.sleep.2015.03.012","article-title":"Associations of the 24-h activity rhythm and sleep with cognition: A population-based study of middle-aged and elderly persons","volume":"16","author":"Luik","year":"2015","journal-title":"Sleep Med"},{"issue":"6315","key":"2025090913321940100_fcaf322-B102","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1126\/science.aah4968","article-title":"Mechanisms linking circadian clocks, sleep, and neurodegeneration","volume":"354","author":"Musiek","year":"2016","journal-title":"Science"},{"issue":"2","key":"2025090913321940100_fcaf322-B103","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s40675-017-0072-5","article-title":"Circadian rhythms in AD pathogenesis: A critical appraisal","volume":"3","author":"Musiek","year":"2017","journal-title":"Curr Sleep Med Rep"},{"issue":"3","key":"2025090913321940100_fcaf322-B104","first-page":"52","article-title":"Circadian rhythm and Alzheimer\u2019s disease","volume":"6","author":"Homolak","year":"2018","journal-title":"Med Sci"},{"key":"2025090913321940100_fcaf322-B105","doi-asserted-by":"crossref","first-page":"101046","DOI":"10.1016\/j.arr.2020.101046","article-title":"Circadian and sleep dysfunction in Alzheimer\u2019s disease","volume":"60","author":"Uddin","year":"2020","journal-title":"Ageing Res Rev"}],"container-title":["Brain Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/7\/5\/fcaf322\/64223384\/fcaf322.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/7\/5\/fcaf322\/64223384\/fcaf322.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T17:32:50Z","timestamp":1757439170000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/braincomms\/article\/doi\/10.1093\/braincomms\/fcaf322\/8249369"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"references-count":105,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,9,1]]}},"URL":"https:\/\/doi.org\/10.1093\/braincomms\/fcaf322","relation":{},"ISSN":["2632-1297"],"issn-type":[{"value":"2632-1297","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025]]},"published":{"date-parts":[[2025]]},"article-number":"fcaf322"}}