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[Preprint]. 2024 Nov 5:2024.11.05.24316677.

doi: 10.1101/2024.11.05.24316677.

Sleep macro-architecture and dementia risk in adults: Meta-analysis of 5 cohorts from the Sleep and Dementia Consortium

Stephanie Yiallourou¹, Andree-Ann Baril^{2

3}, Crystal Wiedner⁴, Jeffrey R Misialek⁵, Christopher E Kline⁶, Stephanie Harrison⁷, Ethan Cannon⁵, Qiong Yang^{8

9}, Rebecca Bernal⁴, Alycia Bisson^{10

11}, Dibya Himali², Marina Cavuoto¹², Antoine Weihs¹³, Alexa Beiser^{2

8

9}, Rebecca F Gottesman¹⁴, Yue Leng¹⁵, Oscar Lopez^{16

17}, Pamela L Lutsey⁵, Shaun M Purcell^{10

18}, Susan Redline^{10

11}, Sudha Seshadri^{2

4

8}, Katie L Stone^{7

19}, Kristine Yaffe²⁰, Sonia Ancoli-Israel²¹, Qian Xiao²², Eleni Okeanis Vaou²³, Jayandra J Himali^{2

4

8

9

24}, Matthew P Pase^{1

2}

Affiliations

¹ School of Psychological Sciences & Turner Institute for Brain and Mental Health, Monash University, Australia.
² Framingham Heart Study, MA, USA.
³ Center for Advances Research in Sleep Medicine, Hôpital du Sacré-Coeur de Montréal, Research Center of the CIUSSS-NIM, Montreal, Canada & Department of Medicine, Université de Montréal, Montreal, Canada.
⁴ Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health San Antonio, San Antonio, TX, USA.
⁵ Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA.
⁶ Department of Health and Human Development, University of Pittsburgh, Pittsburgh, PA, USA.
⁷ California Pacific Medical Center, Research Institute, San Francisco, CA, USA.
⁸ Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
⁹ Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
¹⁰ Division of Sleep and Circadian Disorders, Brigham & Women's Hospital, Boston, MA, USA.
¹¹ Department of Medicine, Harvard Medical School, Boston, MA, USA.
¹² National Ageing Research Institute, Melbourne, Australia.
¹³ German Centre for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Greifswald, Germany & Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
¹⁴ National Institute of Neurological Disorders and Stroke Intramural Research Program, Bethesda, MD, USA.
¹⁵ Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USA.
¹⁶ Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
¹⁷ Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
¹⁸ Department of Psychiatry, Brigham & Women's Hospital, Boston, MA, USA.
¹⁹ Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
²⁰ Departments of Psychiatry, Neurology and Epidemiology, University of California San Francisco, San Francisco, CA, USA.
²¹ Center for Circadian Biology, Department of Psychiatry, University of California, CA, USA.
²² University of Texas Health Science Center at Houston School of Public Health.
²³ Department of Neurology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
²⁴ Department of Population Health Sciences, University of Texas Health Science Center, San Antonio, TX, USA.

PMID: 39802761
PMCID: PMC11722510
DOI: 10.1101/2024.11.05.24316677

Sleep macro-architecture and dementia risk in adults: Meta-analysis of 5 cohorts from the Sleep and Dementia Consortium

Stephanie Yiallourou et al. medRxiv. 2024.

[Preprint]. 2024 Nov 5:2024.11.05.24316677.

doi: 10.1101/2024.11.05.24316677.

Authors

Affiliations

¹ School of Psychological Sciences & Turner Institute for Brain and Mental Health, Monash University, Australia.
² Framingham Heart Study, MA, USA.
³ Center for Advances Research in Sleep Medicine, Hôpital du Sacré-Coeur de Montréal, Research Center of the CIUSSS-NIM, Montreal, Canada & Department of Medicine, Université de Montréal, Montreal, Canada.
⁴ Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health San Antonio, San Antonio, TX, USA.
⁵ Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA.
⁶ Department of Health and Human Development, University of Pittsburgh, Pittsburgh, PA, USA.
⁷ California Pacific Medical Center, Research Institute, San Francisco, CA, USA.
⁸ Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
⁹ Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
¹⁰ Division of Sleep and Circadian Disorders, Brigham & Women's Hospital, Boston, MA, USA.
¹¹ Department of Medicine, Harvard Medical School, Boston, MA, USA.
¹² National Ageing Research Institute, Melbourne, Australia.
¹³ German Centre for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Greifswald, Germany & Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
¹⁴ National Institute of Neurological Disorders and Stroke Intramural Research Program, Bethesda, MD, USA.
¹⁵ Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USA.
¹⁶ Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
¹⁷ Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
¹⁸ Department of Psychiatry, Brigham & Women's Hospital, Boston, MA, USA.
¹⁹ Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
²⁰ Departments of Psychiatry, Neurology and Epidemiology, University of California San Francisco, San Francisco, CA, USA.
²¹ Center for Circadian Biology, Department of Psychiatry, University of California, CA, USA.
²² University of Texas Health Science Center at Houston School of Public Health.
²³ Department of Neurology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
²⁴ Department of Population Health Sciences, University of Texas Health Science Center, San Antonio, TX, USA.

PMID: 39802761
PMCID: PMC11722510
DOI: 10.1101/2024.11.05.24316677

Update in

Sleep architecture and dementia risk in adults: an analysis of 5 cohorts from the Sleep and Dementia Consortium.
Yiallourou S, Baril AA, Wiedner C, Misialek JR, Kline CE, Harrison S, Cannon E, Yang Q, Bernal R, Bisson A, Himali D, Cavuoto M, Weihs A, Beiser A, Gottesman RF, Leng Y, Lopez O, Lutsey PL, Purcell SM, Redline S, Seshadri S, Stone KL, Yaffe K, Ancoli-Israel S, Xiao Q, Vaou EO, Himali JJ, Pase MP. Yiallourou S, et al. Sleep. 2025 Sep 9;48(9):zsaf129. doi: 10.1093/sleep/zsaf129. Sleep. 2025. PMID: 40377976 Free PMC article.

Abstract

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.

Keywords: Alzheimer’s disease; dementia; meta-analysis; sleep; sleep macro-architecture.

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Figures

**Figure 1:. Pooled association between sleep macro-architecture measures and incident dementia.**
Figure depicts the meta-analysis with forest plot. All results were adjusted for age (years), sex (men vs. women), BMI (kg/m²), anti-depressant use (yes vs no), sedative use (yes vs no), and *APOE e4* status (non e4 carrier vs. at least one copy of e4). Cohort studies included: ARIC, Atherosclerosis Risk in Communities study; CHS, Cardiovascular Health Study; FHS, Framingham Heart Study; MrOS, Osteoporotic Fractures in Men Study; SOF, Study of Osteoporotic Fractures. The sleep exposures in each model included: N1, non-rapid eye movement sleep stage 1; N2, non-rapid eye movement sleep stage 2; N3, non-rapid eye movement sleep stage 3; REM, rapid eye movement sleep; WASO, Wake after sleep onset; SME, sleep maintenance efficiency. Note that, square root transformation was applied to N1% and N3% and natural log transformation was applied to SME%, WASO and the AHI due to skewed distributions of these sleep metrics. Dementia case numbers are presented for each cohort with hazard ratio (HR) and 95% confidence intervals (95% CI) for dementia risk. Heterogeneity in effect sizes was determined via the Higgins I² test. Statistical significance, p<0.05.

**Figure 2:. Pooled association between sleep macro-architecture measures and incident dementia – secondary analysis restricted to ARIC, CHS, FHS cohorts.**
Figure depicts the meta-analysis with forest plot limited to three cohorts. All results were adjusted for age (years), sex (men vs. women), BMI (kg/m²), anti-depressant use (yes vs. no), sedative use (yes vs. no), and *APOE e4* status (non e4 carrier vs. at least one copy of e4). Cohort studies included: ARIC, Atherosclerosis Risk in Communities study; CHS, Cardiovascular Health Study and the FHS, Framingham Heart Study. The sleep exposures in each model included: N1, non-rapid eye movement sleep stage 1; N2, non-rapid eye movement sleep stage 2; N3, non-rapid eye movement sleep stage 3; REM, rapid eye movement sleep; WASO, Wake after sleep onset; SME, sleep maintenance efficiency. Note that, square root transformation was applied to N1% and N3% and natural log transformation was applied to SME%, WASO and the AHI due to skewed distributions of these sleep metrics. Dementia case numbers are presented for each cohort with hazard ratio (HR) and 95% confidence intervals (95% CI) for dementia risk. Heterogeneity in effect sizes was determined via the Higgins I² test. Statistical significance, p<0.05.

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This is a preprint.

Sleep macro-architecture and dementia risk in adults: Meta-analysis of 5 cohorts from the Sleep and Dementia Consortium

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Sleep macro-architecture and dementia risk in adults: Meta-analysis of 5 cohorts from the Sleep and Dementia Consortium

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Affiliations

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