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12793

The Link Between Sleep Duration And Severity Of Cognitive Impairment Differs By APOE-e4 Carrier Status In Non-Hispanic Black African Adults

Poster Presenter

Brittany Larsen

Authors

Brittany Larsen, Farid Rajabli, Joshua Akinyemi, Susan Blanton, Debbie Chung, Michael Cuccaro, Giuseppe Tosto, Scott Williams, African Dementia Consortium, William Bush, Brian Kunkle, Jeffrey Vance, Jonathan Haines, Goldie Byrd, Christiane Reitz, Adesola Ogunniyi, Margaret Pericak-Vance, Rufus Akinyemi, Azizi Seixas

Affiliations

, Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USA, John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA; Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA, Department of Epidemiology and Medical Statistics, College of Medicine, University of Ibadan, Ibadan, Nigeria, Gertrude H. Sergievsky Center, Taub Institute for Research on the Aging Brain, Departments of Neurology, Psychiatry, and Epidemiology, College of Physicians and Surgeons, Columbia University, New York, NY, USA, Cleveland Institute for Computational Biology, Department of Population & Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH, USA, John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA; Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA; Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA, Maya Angelou Center for Health Equity, Wake Forest University School of Medicine, Winston-Salem, NC, USA, Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria, Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USA; Department of Informatics and Health Data Science, University of Miami Miller School of Medicine, Miami, FL, USA

Part of Topic

Basic Science and Pathogenesis -> Genetics -> Epigenetics

TITLE: The Relationship Between Sleep Duration and Severity of Cognitive/Functional Impairments Differ by APOE-ε4 Carrier Status in Middle-aged and Elderly Indigenous Africans

OVERALL TAKE-AWAY:

In middle-aged and elderly indigenous Africans, the link between sleep duration and severity of cognitive/functional impairment(s) differed by APOE-ε4 carrier status, underscoring the importance of gene × behavior interactions for cognitive function and Alzheimer’s disease risk.


INTRODUCTION:

•Older adults in sub-Saharan Africa experience a high and rising burden of both sleep disturbance and Alzheimer's disease (AD) yet remain among the most understudied populations for the sleep–dementia relationship.
•APOE-ε4 is the strongest genetic risk factor for late-onset AD, with APOE-ε4/ε4 carriers having the highest genetic risk.
•Short (≤6 h) and long (≥10 h) sleep are both correlated with worse cognitive/functional impairment; however, whether sleep and APOE-ε4 interact remains unclear.
•Objective: To test if the link between sleep duration and severity of cognitive/functional impairments differs by APOE-ε4 carrier status in middle-aged and elderly indigenous Africans.

METHODS:
•Design: Subsample from cross-sectional, population-based DAWN-ADSP study.
•Sample: N=2,121 from Africa; 56.3% female; aged 73.9±9.4y.
•Sleep: Self-reported hours/24 h, then classified as short (≤6 h), average (7–9 h), or long (≥10 h).
•APOE-ε4: non-carriers (50.8%), heterozygotes (38.4%), homozygotes (10.8%).
•Outcomes: Clinical Dementia Rating (CDR) Scale Sum of Boxes and Global Scale; higher scores = worse impairment.
•Analysis: Ordinal logistic models tested if an APOE-ε4 × environmental interaction between self-reported sleep durations and APOE-ε4 status associated with severity of cognitive/functional impairments, including extraneous factors that may influence this link as covariates (age, sex, body mass index, years of education, African subregion (West/East), financial strain, and CVD/hypertension/stroke history); and stratified by APOE-ε4 group.

RESULTS: 

Post hoc APOE-ε4 stratification analysis:

1.Non-carriers: long (but not short) sleep = worse impairment.
2.Heterozygotes: both short and long sleep = worse impairment.
3.Homozygotes: similar levels of cognitive impairment regardless of sleep durations

CONCLUSIONS:

•Sleeping 7–9 hours nightly may be protective in APOE-ε4 heterozygotes, which may reflect that having one APOE-ε4 allele may not significantly disrupt glymphatic clearance of AD-linked neuropathological proteins  (amyloid-β, tau), and obtaining sufficient sleep can still drive effective glymphatic waste removal in these individuals.
•APOE-ε4 homozygotes had the greatest severities of cognitive/functional impairments, regardless of sleep duration, which may reflect significant impairment in glymphatic clearance during sleep and may render sleep as less effective in protecting against cognitive/functional impairments in these individuals.
•Future work: future studies should replicate this work in other ancestral groups and include objective sleep measures.

CONTACT:

Brittany A. Larsen, Ph.D., R.D.N.
Department of Psychiatry & Behavioral Sciences
University of Miami Miller School of Medicine
Email: bal184@miami.edu

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