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

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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.
Authors: John, Amber, Desai, Roopal, Bartres‐Faz, David, Cadar, Dorina, Gaysina, Darya, Gonzalez, Aida Suarez, Marchant, Natalie L., Willroth, Emily, Richards, Marcus, Saunders, Rob, Stott, Joshua
Source: International Journal of Geriatric Psychiatry. Jul2025, Vol. 40 Issue 7, p1-9. 9p.
Subjects: Alzheimer's disease risk factors, Genetics of disease susceptibility, Risk assessment, Satisfaction, Research funding, Deprivation (Psychology), Hospital care, Questionnaires, Sex distribution, Age distribution, Descriptive statistics, Longitudinal method, Uk Biobank Ltd., Odds ratio, Death certificates, Mathematical models, Theory, Confidence intervals, Data analysis software, Disease incidence, Proportional hazards models, Educational attainment, Mental depression, Psychosocial factors
Geographic Terms: United Kingdom
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. Summary: 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. [ABSTRACT FROM AUTHOR]
Copyright of International Journal of Geriatric Psychiatry is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Understanding Interactions Between Life Satisfaction and Genetic Predisposition on Risk of Alzheimer&#39;s Disease up to 14&#160;Years Later: Findings From the UK Biobank.
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  Data: Objectives: Previous research investigating associations between life satisfaction and risk of Alzheimer&#39;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 &lt; 0.001) on incident AD. There was a significant interaction between the two (OR = 1.21, 95% CI = 1.09–1.35, p &lt; 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 &lt; 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. Summary: Higher life satisfaction was linked to a lower risk of Alzheimer&#39;s disease over 14 years, even after adjusting for other factors.A polygenic risk score (PRS) for Alzheimer&#39;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. [ABSTRACT FROM AUTHOR]
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  Data: &lt;i&gt;Copyright of International Journal of Geriatric Psychiatry is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder&#39;s express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.&lt;/i&gt; (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=186954573
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      – Type: doi
        Value: 10.1002/gps.70120
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      – Code: eng
        Text: English
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        PageCount: 9
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    Subjects:
      – SubjectFull: Alzheimer's disease risk factors
        Type: general
      – SubjectFull: Genetics of disease susceptibility
        Type: general
      – SubjectFull: Risk assessment
        Type: general
      – SubjectFull: Satisfaction
        Type: general
      – SubjectFull: Research funding
        Type: general
      – SubjectFull: Deprivation (Psychology)
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      – SubjectFull: Hospital care
        Type: general
      – SubjectFull: Questionnaires
        Type: general
      – SubjectFull: Sex distribution
        Type: general
      – SubjectFull: Age distribution
        Type: general
      – SubjectFull: Descriptive statistics
        Type: general
      – SubjectFull: Longitudinal method
        Type: general
      – SubjectFull: Uk Biobank Ltd.
        Type: general
      – SubjectFull: Odds ratio
        Type: general
      – SubjectFull: Death certificates
        Type: general
      – SubjectFull: Mathematical models
        Type: general
      – SubjectFull: Theory
        Type: general
      – SubjectFull: Confidence intervals
        Type: general
      – SubjectFull: Data analysis software
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      – SubjectFull: Disease incidence
        Type: general
      – SubjectFull: Proportional hazards models
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      – SubjectFull: Educational attainment
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      – SubjectFull: Mental depression
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      – SubjectFull: Psychosocial factors
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      – SubjectFull: United Kingdom
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      – TitleFull: Understanding Interactions Between Life Satisfaction and Genetic Predisposition on Risk of Alzheimer's Disease up to 14 Years Later: Findings From the UK Biobank.
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              Text: Jul2025
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