John, Amber;
Desai, Roopal;
Bartres‐Faz, David;
Cadar, Dorina;
Gaysina, Darya;
Gonzalez, Aida Suarez;
Marchant, Natalie L;
... Stott, Joshua; + view all
(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)
, Article e70120. 10.1002/gps.70120.
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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.
| Type: | Article |
|---|---|
| Title: | Understanding Interactions Between Life Satisfaction and Genetic Predisposition on Risk of Alzheimer's Disease up to 14 Years Later: Findings From the UK Biobank |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/gps.70120 |
| Publisher version: | https://doi.org/10.1002/gps.70120 |
| Language: | English |
| Additional information: | © 2025 The Author(s). International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences > Clinical, Edu and Hlth Psychology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10210587 |
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