ArticleBMC medicine2025
Sleep quality, APOE ε4, and Alzheimer's disease: associations from two prospective cohort studies and mechanisms by plasma proteomic analysis.
Article in BMC medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The role of APOE ε4 in modulating the relationship between non-genetic risk factors and dementia: a system review and meta-analysis.Journal of neurology · 2025Pooled it
- Smoking Interacts WithBiological psychiatry global open science · 2026Article
- Article
- Sleep complaints and genetic risk of Alzheimer's disease in older women: associations with memory and tau deposition.The journal of prevention of Alzheimer's disease · 2026Article
- Differential associations of lipid profile and genetic susceptibility with sleep duration.Lipids in health and disease · 2026Article
- Associations between sleep disturbance and cerebrospinal fluid Aβ, and shared proteomic signatures in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Associations and interaction effects of socioeconomic, lifestyle, and genetic factors on intrinsic capacity.The journals of gerontology. Series A, Biological sciences and medical sciences · 2026Article
- Systematic Review on the Association Between Sleep and the Risk of Alzheimer's Disease: An Evolutionary Perspective.Evolutionary applications · 2026Review
- Sleep electroencephalography-derived brain health and long-term cognitive decline in community-dwelling adults.Sleep advances : a journal of the Sleep Research Society · 2026Article
- Depression severity and sleep efficiency's associations with amyloid burden are additive but dependent on underlying genetic risk in late life depression.Alzheimer's & dementia (Amsterdam, Netherlands)Article
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Authors and funding
12 authors.
Funding
Abstract
backgroundThe relationship between sleep quality and Alzheimer's disease (AD), and its interaction with genetic susceptibility, remains unclear. Our study explores the complex association between sleep quality and AD risk, focusing on the moderating role of the APOE ε4 allele.
methodsLinear regression models, linear mixed-effects models, and Cox proportional hazard models were conducted in 321,905 non-demented participants from UK Biobank (UKB, mean age = 56.49, mean follow-up: 12.3 years) and 1,598 non-demented participants (mean age = 73.19, mean follow-up: 3.90 years) from Alzheimer's Disease Neuroimaging Initiative (ADNI). The interaction terms of sleep by APOE ε4 status were added in all analyses and stratified analyses were further performed. Proteomic and bioinformatic analyses were conducted to explore the biological mechanisms by which sleep and its interaction with APOE ε4 influence the development of AD.
resultsPoor sleep quality was significantly associated with worse cognition, faster hippocampal atrophy, and increased AD risk (HR = 1.05 in UKB and HR = 1.37 in ADNI). Notably, these associations were intensified in APOE ε4 carriers. Proteomic analyses identified eleven proteins linked to both poor sleep and AD risk (P < 1.72 × 10
conclusionsPoor sleep is associated with increased risk of AD, possibly by dysregulating peripheral inflammatory responses and metabolic pathways. The interaction between poor sleep and APOE ε4 may further enhance AD risk. Future studies are warranted to test whether this interaction was driven by neuroinflammation.
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