Study objectives: Poor sleep may play a role in the risk of dementia. However, few studies have investigated the association between polysomnography (PSG)-derived sleep architecture and dementia incidence. We examined the relationship between sleep macro-architecture and dementia incidence across five US-based cohort studies from the Sleep and Dementia Consortium (SDC). Methods: Percent of time spent in stages of sleep (N1, N2, N3, REM sleep), wake after sleep onset and sleep maintenance efficiency were derived from a single night home-based PSG. Dementia was ascertained in each cohort using its cohort-specific criteria. Each cohort performed Cox proportional hazard regressions for each sleep exposure and incident dementia, adjusting for age, sex, body mass index, anti-depressant use, sedative use, and APOE e4 status. Results were then pooled in random effects meta-analyses. Results: The pooled sample comprised 4,657 participants (30% women) aged ≥60 years (mean age was 74 years at sleep assessment). There were 998 (21.4%) dementia cases (median follow-up time of 5 to 19 years). Pooled effects of the five cohorts showed no association between sleep architecture and incident dementia. When meta-analyses were restricted to the three cohorts which had dementia case ascertainment based on DSM-IV/V criteria (n=2,374), higher N3% was marginally associated with an increased risk of dementia (HR: 1.06; 95%CI: 1.00-1.12, per percent increase N3, p=0.050). Conclusions: There were no consistent associations between sleep macro-architecture measured and the risk of incident dementia. Implementing more nuanced sleep metrics remains an important next step for uncovering more about sleep-dementia associations.

Financial disclosures: Dr Seshadri reports receiving consulting fees from Biogen and Eisai outside the submitted work. Dr Baril reports receiving speaker fees from Eisai outside of the present work. Dr Redline reports receiving grants from the National Institutes of Health (NIH) during the conduct of the study and personal fees from Jazz Pharmaceuticals, Eli Lilly, and Apnimed outside the submitted work. Non-financial disclosures: None

SDC: The SDC is funded by the NIA (R01 AG062531). This work is also made possible by grants from the NIA to the Cross Cohorts Consortium (CCC) (AG059421) and by the Cohorts for Age and Aging Research in Genomic Epidemiology (CHARGE) infrastructure grant from the NHLBI (HL105756). FHS: This work was made possible by grants from the National Institutes of Health (N01-HC-25195, HHSN268201500001I, 75N92019D00031) and the National Institute on Aging (AG059421, AG054076, AG049607, AG033090, AG066524, NS017950, P30AG066546, UF1NS125513). ARIC: The ARIC portion of the SHHS was supported by National Heart, Lung, and Blood Institute cooperative agreements U01HL53934 (University of Minnesota) and U01HL64360 (Johns Hopkins University). The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under Contract nos. (75N92022D00001, 75N92022D00002, 75N92022D00003, 75N92022D00004, 75N92022D00005). The authors thank the staff and participants of the ARIC study for their important contributions. ARIC Neurocognitive (ARIC-NCS) for selected components of Visit 5 and 7 and all of Visits 6-8 The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (75N92022D00001, 75N92022D00002, 75N92022D00003, 75N92022D00004, 75N92022D00005). The ARIC Neurocognitive Study is supported by U01HL096812, U01HL096814, U01HL096899, U01HL096902, and U01HL096917 from the NIH (NHLBI, NINDS, NIA and NIDCD). The authors thank the staff and participants of the ARIC study for their important contributions. CHS: This research was supported by contracts HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, 75N92021D00006, and grants U01HL080295 and U01HL130114 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Support for cognitive measures was provided by R01AG15928. Additional support was provided by R01AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. MrOS: MrOS is supported by National Institutes of Health funding. The following institutes provide support: the National Institute on Aging (NIA), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Center for Advancing Translational Sciences (NCATS), and NIH Roadmap for Medical Research under the following grant numbers: U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, and UL1 TR0 The National Heart, Lung, and Blood Institute (NHLBI) provides funding for the MrOS Sleep ancillary study "Outcomes of Sleep Disorders in Older Men" under the following grant numbers: R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, and R01 HL07083900128. SOF: SOF is supported by National Institutes of Health funding. The National Institute on Aging (NIA) provides support under the following grant numbers: R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, R01 AG027576, and R01 AG026720. Other: Dr Yiallourou are funded by the American Alzheimer's Association (AARG-NTF-22-971405). Dr. Pase is supported by the National Health and Medical Research Council of Australia (GTN2009264; GTN1158384). Dr. Cavuoto and Dr. Pase are supported by a Dementia Australia Research Foundation award (Lucas' Papaw Remedies Project Grant). Dr. Baril is funded by grants from the Alzheimer Society of Canada, Canadian Institutes of Health Research, and Sleep Research Society Foundation. Drs. Seshadri and Himali are partially supported by the South Texas Alzheimer's Disease Center (1P30AG066546-01A1) and The Bill and Rebecca Reed Endowment for Precision Therapies and Palliative Care. Dr. Seshadri is also supported by an endowment from the Barker Foundation as the Robert R Barker Distinguished University Professor of Neurology, Psychiatry and Cellular and Integrative Physiology and Dr. Himali by an endowment from the William Castella family as William Castella Distinguished University Chair for Alzheimer's Disease Research. Dr. Redline is partially funded by NIA AG 070867. Dr. Yaffe is partially funded by NIA R35 AG071916. Dr. Lutsey is partially supported by K24 HL159246. Dr. Gottesman is supported by the NINDS Intramural Research Program. Dr. Purcell is partially funded by NIH NHLBI R01HL146339, NIH NIA 070867, and NIH NIMHD MD012738.

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