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
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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.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>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, <i>p</i> = 0.001) and the AD PRS (OR = 2.26, 95% CI = 2.12–2.40, <i>p</i> < 0.001) on incident AD. There was a significant interaction between the two (OR = 1.21, 95% CI = 1.09–1.35, <i>p</i> < 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, <i>p</i> < 0.001; high: OR = 0.88, 95% CI = 0.75–1.04, <i>p</i> = 0.13).</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>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. 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引用次数: 0
摘要
目的以往调查生活满意度与阿尔茨海默病（AD）风险之间关系的研究结果不一。这种关联可能因阿尔茨海默病的遗传风险而异。本研究的目的是测试生活满意度和遗传易感性对未来AD诊断发病率的相互作用。方法数据来自英国生物银行（UK Biobank）的66,668名60岁以上的参与者。参与者在基线时参加了一个评估中心，数据与14年后的住院数据和死亡记录相关联。使用Cox比例风险模型来检验生活满意度与AD多基因风险评分（PRS）在AD偶发诊断中的相互作用。模型也按照AD的遗传风险分层运行。结果调整了年龄、性别、种族、贫困、教育程度和抑郁的模型显示，生活满意度（OR = 0.78, 95% CI = 0.68-0.90, p = 0.001）和AD PRS (OR = 2.26, 95% CI = 2.12-2.40, p <；0.001)。两者之间存在显著的交互作用(OR = 1.21, 95% CI = 1.09-1.35, p <；0.001)。分层模型显示，生活满意度与低遗传风险组的低AD发生率相关，但与高遗传风险组无关(低：OR = 0.56, 95% CI = 0.42-0.75, p <；0.001;高：OR = 0.88, 95% CI = 0.75-1.04, p = 0.13)。结论AD的遗传风险改变了生活满意度与AD风险之间的关系。这表明遗传风险可能会削弱生活满意度和AD风险之间的联系。这些发现澄清了之前关于这一主题的研究结果，并可能有助于未来更有针对性地预防阿尔茨海默病。
Understanding Interactions Between Life Satisfaction and Genetic Predisposition on Risk of Alzheimer's Disease up to 14 Years Later: Findings From the UK Biobank
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.
期刊介绍：
The rapidly increasing world population of aged people has led to a growing need to focus attention on the problems of mental disorder in late life. The aim of the Journal is to communicate the results of original research in the causes, treatment and care of all forms of mental disorder which affect the elderly. The Journal is of interest to psychiatrists, psychologists, social scientists, nurses and others engaged in therapeutic professions, together with general neurobiological researchers.
The Journal provides an international perspective on the important issue of geriatric psychiatry, and contributions are published from countries throughout the world. Topics covered include epidemiology of mental disorders in old age, clinical aetiological research, post-mortem pathological and neurochemical studies, treatment trials and evaluation of geriatric psychiatry services.
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