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

Amber John; Roopal Desai; David Bartres-Faz; Dorina Cadar; Darya Gaysina; Aida Suarez Gonzalez; Natalie L Marchant; Emily Willroth; Marcus Richards; Rob Saunders; Joshua Stott

doi:10.1002/gps.70120

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

Int J Geriatr Psychiatry. 2025 Jul;40(7):e70120. doi: 10.1002/gps.70120.

Authors

Amber John^{1

2}, Roopal Desai², David Bartres-Faz^{2

3}, Dorina Cadar⁴, Darya Gaysina⁵, Aida Suarez Gonzalez⁶, Natalie L Marchant⁷, Emily Willroth⁸, Marcus Richards⁹, Rob Saunders¹⁰, Joshua Stott²

Affiliations

¹ Psychology Department, University of Liverpool, Liverpool, UK.
² ADAPT Lab, Research Department of Clinical, Educational and Health Psychology, UCL, London, UK.
³ Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
⁴ CEDAR Lab, Department of Clinical Neuroscience, Brighton and Sussex Medical School (BSMS), University of Sussex, Brighton, UK.
⁵ EDGE Lab, School of Psychology, University of Sussex, Brighton, UK.
⁶ Dementia Research Centre, UCL, London, UK.
⁷ Division of Psychiatry, UCL, London, UK.
⁸ Psychological & Brain Sciences, Washington University in St. Louis, St. Louis, Washington, USA.
⁹ MRC Unit for Lifelong Health and Ageing at UCL, University College London, London, UK.
¹⁰ CORE Data Lab, Research Department of Clinical, Centre for Outcomes and Research Effectiveness, Educational and Health Psychology, UCL, London, UK.

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.

Keywords: Alzheimer's disease; UK biobank; life satisfaction; longitudinal.

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease* / epidemiology
Alzheimer Disease* / genetics
Alzheimer Disease* / psychology
Biological Specimen Banks
Female
Genetic Predisposition to Disease*
Humans
Incidence
Male
Middle Aged
Personal Satisfaction*
Proportional Hazards Models
Risk Factors
UK Biobank
United Kingdom / epidemiology

Abstract

MeSH terms

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