Objective We aimed to investigate the association of cardiorespiratory fitness (CRF) with cognitive function and dementia risk, taking genetic predisposition for dementia into account. Methods Within the UK Biobank, 61 214 dementia-free participants aged 39–70 years were followed for up to 12 years. CRF score was estimated using a 6 min submaximal exercise test on a stationary bike and divided into tertiles (ie, low, moderate, and high; standardised by age and sex). Global cognitive function was evaluated at baseline. Dementia was identified based on medical history and medical records. Genetic predisposition for dementia was estimated using the polygenic risk score for Alzheimer’s disease (PRSAD), tertiled as low, moderate, or high. Data were analysed using linear regression, Poisson regression, and Laplace regression. Results Compared with low CRF, high CRF was related to better global cognitive function (β=0.05, 95% CI 0.04 to 0.07). Over the follow-up period, 553 individuals developed dementia. Compared with low CRF, the incidence rate ratio (IRR) of all dementia was 0.60 (95% CI 0.48 to 0.76) for high CRF, and the onset of all dementia was delayed by 1.48 (95% CI 0.58 to 2.39) years among people with high versus low CRF. Among people with a moderate/high polygenic risk score, high CRF attenuated all dementia risk by 35% (IRR 0.65, 95% CI 0.52 to 0.83). Conclusion High CRF is associated with better cognitive performance at baseline, and lower dementia risk long-term. High CRF could mitigate the impact of genetic predisposition on the development of dementia by 35%. Data may be obtained from a third party and are not publicly available.

中文翻译：

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心肺健康与不同遗传易感性水平的痴呆风险的关联：一项基于社区的大型纵向研究


目的 我们旨在探讨心肺健康 （CRF） 与认知功能和痴呆风险的关系，同时考虑到痴呆的遗传易感性。方法 在英国生物样本库中，对 61 214 名年龄在 39-70 岁之间的无痴呆参与者进行了长达 12 年的随访。使用固定自行车上的 6 分钟次极量运动测试估计 CRF 评分，并分为三分位数（即低、中和高;按年龄和性别标准化）。在基线时评估整体认知功能。根据病史和病历确定痴呆。使用阿尔茨海默病多基因风险评分 （PRSAD） 估计痴呆的遗传易感性，分为低、中或高。使用线性回归、泊松回归和拉普拉斯回归分析数据。结果 与低 CRF 相比，高 CRF 与更好的整体认知功能相关 （β=0.05,95% CI 0.04 至 0.07）。在随访期间，553 人患上了痴呆。与低 CRF 相比，高 CRF 患者所有痴呆的发病率比 （IRR） 为 0.60 （95% CI 0.48 至 0.76），高 CRF 患者与低 CRF 患者的所有痴呆发作延迟 1.48 年 （95% CI 0.58 至 2.39）。在多基因风险评分中/高的人群中，高 CRF 使所有痴呆风险降低了 35% （IRR 0.65,95% CI 0.52 至 0.83）。结论 高 CRF 与基线时较好的认知表现相关，且长期痴呆风险较低。高 CRF 可以将遗传易感性对痴呆发展的影响减轻 35%。数据可能从第三方获得，并且不会公开。