Understanding Interactions Between Life Satisfaction and Genetic Predisposition on Risk of Alzheimer's Disease up to 14 Years Later: Findings From the UK Biobank


John, A ORCID: 0000-0002-8207-7698, Desai, R ORCID: 0000-0003-4221-1546, Bartres-Faz, D, Cadar, D, Gaysina, D, Gonzalez, AS, Marchant, NL, Willroth, E, Richards, M, Saunders, R et al (show 1 more authors) (2025) Understanding Interactions Between Life Satisfaction and Genetic Predisposition on Risk of Alzheimer's Disease up to 14 Years Later: Findings From the UK Biobank International Journal of Geriatric Psychiatry, 40 (7). e70120-. ISSN 0885-6230, 1099-1166

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Abstract

Objectives: Previous research investigating associations between life satisfaction and risk of Alzheimer's disease (AD) has been mixed. This association may differ depending on genetic risk for AD. The aim of this study was to test interactions between life satisfaction and genetic predisposition on the future incidence of AD diagnosis. Methods: Data were used from 66,668 participants aged 60+ from the UK Biobank. Participants attended an assessment centre at baseline, and data were linked to hospital admissions data and death records up to 14 years later. Cox proportional hazards models were used to test interactions between life satisfaction and a polygenic risk score (PRS) for AD on incident AD diagnosis. Models were also run stratified by genetic risk for AD. Results: Models adjusted for age, sex, ethnicity, deprivation, education, and depression showed main effects of both life satisfaction (OR = 0.78, 95% CI = 0.68–0.90, p = 0.001) and the AD PRS (OR = 2.26, 95% CI = 2.12–2.40, p < 0.001) on incident AD. There was a significant interaction between the two (OR = 1.21, 95% CI = 1.09–1.35, p < 0.001). Stratified models showed that life satisfaction was associated with lower incident AD in the low, but not in the high genetic risk group (low: OR = 0.56, 95% CI = 0.42–0.75, p < 0.001; high: OR = 0.88, 95% CI = 0.75–1.04, p = 0.13). Conclusions: Results show that genetic risk for AD modified the relationship between life satisfaction and the risk of AD. This suggests that genetic risk may weaken associations between life satisfaction and AD risk. The findings clarify the mixed results of previous research on this topic and may contribute to more tailored approaches to the prevention of AD in the future.

Item Type: Article
Uncontrolled Keywords: Humans, Alzheimer Disease, Genetic Predisposition to Disease, Incidence, Proportional Hazards Models, Risk Factors, Personal Satisfaction, Aged, Aged, 80 and over, Middle Aged, Biological Specimen Banks, Female, Male, United Kingdom, UK Biobank
Divisions: Faculty of Health & Life Sciences
Faculty of Health & Life Sciences > Inst. Population Health
Depositing User: Symplectic Admin
Date Deposited: 11 Jul 2025 08:53
Last Modified: 23 Jan 2026 18:08
DOI: 10.1002/gps.70120
Open Access URL: https://doi.org/10.1002/gps.70120
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3193680
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