Observational studyPloS one2025
Unequal expression: Social position modulates APOE genotype risk of dementia.
Observational study in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed.
- Shifting the emphasis of brain health literacy from individuals to systems to reduce inequalities.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
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Authors and funding
3 authors.
Funding
Abstract
backgroundAlthough social position plays a pivotal role in cognitive aging, most dementia prevention strategies and risk prediction models continue to emphasize biomedical and genetic factors (particularly APOE status). This disconnect raises critical questions about how social environments may shape the effect of genetic risk on dementia. We examined how APOE alleles interact with social adversity to determine dementia risk.
methodsWe conducted an observational analysis using two large cohort studies-the Health and Retirement Study (HRS) and the English Longitudinal Study of Ageing (ELSA)-including individuals aged 55 years or older without dementia at baseline. A social adversity index was constructed based on the five domains of social determinants of health outlined in the Healthy People 2030 framework: education access, economic stability, healthcare quality, neighborhood environment, and social context. Participants were classified as having low (APOE-ε2), intermediate (APOE-ε3/ε3), or high (APOE-ε4) genetic risk of dementia. Dementia was ascertained via clinical diagnosis, cognitive testing, or validated caregiver report. Cox proportional hazards models were used in each cohort, and estimates were pooled using random-effects adjusting for covariates.
resultsA total of 9,849 participants (HRS = 5,797; ELSA = 4,052) were followed for up to 12 years. Genetic effects were most pronounced among individuals with social advantage (reference: APOE-ε3/ε3 with social advantage; APOE-ε2 HR = 0.67, 95%CI = 0.48-0.93; APOE-ε4 HR = 1.68, 95%CI = 1.37-2.06). In contrast, those experiencing high social adversity had elevated dementia risk regardless of genotype (reference: APOE-ε3/ε3 with social advantage; APOE-ε2 HR = 3.26, 95%CI = 2.06-5.16; APOE-ε3/ε3 HR = 3.12, 95%CI = 2.47-3.95; APOE-ε4 HR = 3.21, 95%CI = 2.34-4.41). Notably, individuals with high genetic risk but social advantage had a lower dementia risk than those with low genetic risk but high social adversity.
conclusionsThe influence of genetic risk on dementia appears shaped by social position. Addressing social adversity may reduce dementia risk across genotypes and enhance equity in dementia prevention strategies.
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