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

## TL;DR

Higher life satisfaction is linked to lower Alzheimer's risk, but this effect is weaker in people with high genetic risk for the disease.

## Contribution

The study reveals a gene-environment interaction between life satisfaction and genetic predisposition in Alzheimer's risk.

## Key findings

- Life satisfaction was associated with lower Alzheimer's risk in low genetic risk groups but not in high genetic risk groups.
- A polygenic risk score for Alzheimer's was strongly associated with increased disease risk.
- The interaction between life satisfaction and genetic risk suggests personalized prevention strategies may be needed.

## Abstract

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.

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.

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).

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.

Higher life satisfaction was linked to a lower risk of Alzheimer's disease over 14 years, even after adjusting for other factors.A polygenic risk score (PRS) for Alzheimer's was associated with an increased risk of developing the condition.There was a gene‐environment interaction, with stronger associations between life satisfaction and AD risk in those with low genetic risk.Life satisfaction may be associated with reduced AD risk, but this relationship is weaker in those with high genetic risk, suggesting a need for personalised prevention strategies.

Higher life satisfaction was linked to a lower risk of Alzheimer's disease over 14 years, even after adjusting for other factors.

A polygenic risk score (PRS) for Alzheimer's was associated with an increased risk of developing the condition.

There was a gene‐environment interaction, with stronger associations between life satisfaction and AD risk in those with low genetic risk.

Life satisfaction may be associated with reduced AD risk, but this relationship is weaker in those with high genetic risk, suggesting a need for personalised prevention strategies.