Association of Lifestyle and Genetic Risk With Incidence of Dementia
Association of Lifestyle and Genetic Risk With Incidence of Dementia
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DOI：
10.1001/jama.2019.9879
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发表时间：
2019-08-06
影响因子：
120.7
通讯作者：
Llewellyn, David J.
中科院分区：
文献类型：
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作者：
Lourida, Ilianna;Hannon, Eilis;Llewellyn, David J.
重要信息遗传因素会增加患痴呆症的风险，但生活方式因素能在多大程度上抵消这一风险尚不清楚。目的探讨无论遗传风险如何，健康的生活方式是否与较低的痴呆症风险相关。设计、设置和参与者一项回溯性队列研究，包括至少60岁的欧洲血统的成年人，在基线水平上没有认知障碍或痴呆。参与者从2006年到2010年加入了英国生物库的研究，并被跟踪调查到2016年或2017年。低(最低五分位数)、中等(二至四分位数)和高(最高五分位数)风险类别的痴呆症的多基因风险评分，以及加权的健康生活方式评分，包括当前不吸烟、定期体育活动、健康饮食和适度饮酒，分为良好、中等和不良生活方式。主要结果和措施通过住院和死亡记录确定的意外全因痴呆。结果196383例受试者(平均年龄64.12.9岁，女性占52.7%)获得1545433人年(中位数8.07.4年~8.6年)的随访。总体而言，68.1%的参与者遵循良好的生活方式，23.6%的人遵循中等生活方式，8.2%的人遵循不好的生活方式。20%的多基因风险评分较高，60%的风险评分中等，20%的风险评分较低。在遗传风险高的参与者中，1.23%(95%CI，1.13%-1.35%)发生痴呆，而低遗传风险参与者(调整后的危险比，1.91[95%CI，1.64-2.23])的发病率为0.63%(95%CI，0.56%-0.71%)。在高遗传风险和不良生活方式的参与者中，1.78%(95%CI，1.38%-2.28%)发生痴呆，而低遗传风险和良好生活方式的参与者(危险比，2.83[95%CI，2.09-3.83])发生痴呆的比例为0.56%(95%CI，0.48%-0.66%)。遗传风险和生活方式因素之间没有显著的交互作用(P=0.99)。在具有高遗传风险的参与者中，生活方式良好的参与者中有1.13%(95%CI，1.01%~1.26%)发生痴呆，而生活方式不良的参与者中有1.78%(95%CI，1.38%~2.28%)发生痴呆(危险比0.68[95%CI，0.51~0.90])。结论和相关性在没有认知障碍或痴呆的老年人中，不良的生活方式和高遗传风险都与较高的痴呆风险显著相关。在遗传风险较高的参与者中，良好的生活方式与较低的痴呆症风险有关。
ImportanceGenetic factors increase risk of dementia, but the extent to which this can be offset by lifestyle factors is unknown. ObjectiveTo investigate whether a healthy lifestyle is associated with lower risk of dementia regardless of genetic risk. Design, Setting, and ParticipantsA retrospective cohort study that included adults of European ancestry aged at least 60 years without cognitive impairment or dementia at baseline. Participants joined the UK Biobank study from 2006 to 2010 and were followed up until 2016 or 2017. ExposuresA polygenic risk score for dementia with low (lowest quintile), intermediate (quintiles 2 to 4), and high (highest quintile) risk categories and a weighted healthy lifestyle score, including no current smoking, regular physical activity, healthy diet, and moderate alcohol consumption, categorized into favorable, intermediate, and unfavorable lifestyles. Main Outcomes and MeasuresIncident all-cause dementia, ascertained through hospital inpatient and death records. ResultsA total of 196383 individuals (mean [SD] age, 64.1 [2.9] years; 52.7% were women) were followed up for 1545433 person-years (median [interquartile range] follow-up, 8.0 [7.4-8.6] years). Overall, 68.1% of participants followed a favorable lifestyle, 23.6% followed an intermediate lifestyle, and 8.2% followed an unfavorable lifestyle. Twenty percent had high polygenic risk scores, 60% had intermediate risk scores, and 20% had low risk scores. Of the participants with high genetic risk, 1.23% (95% CI, 1.13%-1.35%) developed dementia compared with 0.63% (95% CI, 0.56%-0.71%) of the participants with low genetic risk (adjusted hazard ratio, 1.91 [95% CI, 1.64-2.23]). Of the participants with a high genetic risk and unfavorable lifestyle, 1.78% (95% CI, 1.38%-2.28%) developed dementia compared with 0.56% (95% CI, 0.48%-0.66%) of participants with low genetic risk and favorable lifestyle (hazard ratio, 2.83 [95% CI, 2.09-3.83]). There was no significant interaction between genetic risk and lifestyle factors (P=.99). Among participants with high genetic risk, 1.13% (95% CI, 1.01%-1.26%) of those with a favorable lifestyle developed dementia compared with 1.78% (95% CI, 1.38%-2.28%) with an unfavorable lifestyle (hazard ratio, 0.68 [95% CI, 0.51-0.90]). Conclusions and RelevanceAmong older adults without cognitive impairment or dementia, both an unfavorable lifestyle and high genetic risk were significantly associated with higher dementia risk. A favorable lifestyle was associated with a lower dementia risk among participants with high genetic risk.