ArticleAlzheimer's research & therapy2023
Leading mediators of sex differences in the incidence of dementia in community-dwelling adults in the UK Biobank: a retrospective cohort study.
Article in Alzheimer's research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 15 citations in OpenAlex.
- Sex differences in dementia risk: considering underlying medical conditions.Alzheimer's research & therapy · 2025Observational
- Outdoor physical activity, residential green spaces and the risk of dementia in the UK Biobank cohort.Communications medicine · 2025Article
- TET2-mutant myeloid cells mitigate Alzheimer's disease progression via CNS infiltration and enhanced phagocytosis in mice.Cell stem cell · 2025Article
- Development of an individualized dementia risk prediction model using deep learning survival analysis incorporating genetic and environmental factors.Alzheimer's research & therapy · 2024Article
- Klebsiella pneumoniae infection increases risk of Alzheimer's Disease in the UK Biobank cohort.medRxiv : the preprint server for health sciences · 2024Article
- RPTOR Is an Alzheimer's Disease Susceptibility Gene Associated with the Risk Factors Body Mass Index and Infectious Encephalitis.Journal of Alzheimer's disease reports · 2024Article
- Gender Selectively Mediates the Association Between Sex and Memory in Cognitively Normal Older Adults.Innovation in aging · 2024Article
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Authors and funding
14 authors at 8 institutions in 2 countries.
Funding
Abstract
backgroundLittle is known regarding whether sex assigned at birth modifies the association between several predictive factors for dementia and the risk of dementia itself.
methodsOur retrospective cohort study included 214,670 men and 214,670 women matched by age at baseline from the UK Biobank. Baseline data were collected between 2006 and 2010, and incident dementia was ascertained using hospital inpatient or death records until January 2021. Mediation analysis was tested for 133 individual factors.
resultsOver 5,117,381 person-years of follow-up, 5928 cases of incident all-cause dementia (452 cases of young-onset dementia, 5476 cases of late-onset dementia) were documented. Hazard ratios (95% CI) for all-cause, young-onset, and late-onset dementias associated with the male sex (female as reference) were 1.23 (1.17-1.29), 1.42 (1.18-1.71), and 1.21 (1.15-1.28), respectively. Out of 133 individual factors, the strongest mediators for the association between sex and incident dementia were multimorbidity risk score (percentage explained (95% CI): 62.1% (45.2-76.6%)), apolipoprotein A in the blood (25.5% (15.2-39.4%)), creatinine in urine (24.9% (16.1-36.5%)), low-density lipoprotein cholesterol in the blood (23.2% (16.2-32.1%)), and blood lymphocyte percentage (21.1% (14.5-29.5%)). Health-related conditions (percentage (95% CI) explained: 74.4% (51.3-88.9%)) and biomarkers (83.0% (37.5-97.5%)), but not lifestyle factors combined (30.1% (20.7-41.6%)), fully mediated sex differences in incident dementia. Health-related conditions combined were a stronger mediator for late-onset (75.4% (48.6-90.8%)) than for young-onset dementia (52.3% (25.8-77.6%)), whilst lifestyle factors combined were a stronger mediator for young-onset (42.3% (19.4-69.0%)) than for late-onset dementia (26.7% (17.1-39.2%)).
conclusionsOur analysis matched by age has demonstrated that men had a higher risk of all-cause, young-onset, and late-onset dementias than women. This association was fully mediated by health-related conditions or blood/urinary biomarkers and largely mediated by lifestyle factors. Our findings are important for understanding potential mechanisms of sex in dementia risk.
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