BACKGROUND AND OBJECTIVES The 21-point Brain Care Score (BCS) is an index that ranks behaviors and clinical measurements with the aim of encouraging lifestyle adjustments to lower the incidence of age-related brain disease, including stroke, late-life depression (LLD), and dementia. A higher BCS at baseline is associated with a lower risk of these outcomes. We aimed to investigate whether the associations between BCS and stroke, LLD, and dementia risks are independent of genetic predisposition for these conditions and quantify the effect of healthy lifestyle across genetic risk distributions for these outcomes. METHODS Using the UK Biobank (UKB) prospective cohort study, we computed baseline BCSs and polygenic scores to estimate genetic predisposition for stroke and LLD and APOE ε allele status to stratify dementia risk. As for outcomes again in UKB, we measured incidence of stroke, LLD, and dementia. We used multivariate Cox proportional hazard models to assess associations between BCS, genetic predisposition, and these outcomes. We also conducted stratified and interaction analyses to estimate the incidence of these outcomes across quartiles of genetic risk and BCS. RESULTS We included 368,340 UKB participants (median age 58 years (interquartile range 51-63 years), 46.3% male). Independent of genetic risk, a 5-point increase in BCS corresponded to lowered hazards of stroke (hazard ratio [HR] 0.70, 95% CI 0.68-0.73), LLD (HR 0.65, 95% CI 0.63-0.67), and dementia (HR 0.82, 95% CI 0.78-0.85). Incidences of all 3 outcomes were higher among participants with high genetic risk of these outcomes. However, these increased risks were offset for individuals with a higher BCS (incidence rates per 1,000 person-years were 2.76 vs 1.19 for stroke, 7.34 vs 4.46 for LLD, and 3.64 vs 2.05 for dementia, when comparing low and high BCS). DISCUSSION Across different genetic predispositions for stroke, LLD, and dementia, healthier lifestyle behaviors are protective for brain health, demonstrating the nondeterminism of genetic risk. Furthermore, differences in BCS behave as aggregate risk estimators of all 3 outcomes. Further work is needed to prospectively investigate the utility and performance of the BCS as a targeted intervention in populations at elevated genetic risk of age-related brain disease.

中文翻译：

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与健康相关的行为和常见年龄相关脑部疾病的风险，跨越遗传风险的严重程度。


背景和目标 21 分制的大脑护理评分 （BCS） 是一个对行为和临床测量进行排名的指数，旨在鼓励调整生活方式以降低与年龄相关的脑病的发生率，包括中风、晚年抑郁症 （LLD） 和痴呆。基线时较高的 BCS 与这些结果的风险较低相关。我们旨在调查 BCS 与中风、LLD 和痴呆风险之间的关联是否独立于这些疾病的遗传易感性，并量化健康生活方式在遗传风险分布中对这些结果的影响。方法 使用英国生物样本库 （UKB） 前瞻性队列研究，我们计算基线 BCS 和多基因评分，以估计中风的遗传易感性，以及 LLD 和 APOE ε等位基因状态，以对痴呆风险进行分层。至于 UKB 的结局，我们测量了中风、LLD 和痴呆的发生率。我们使用多变量 Cox 比例风险模型来评估 BCS 、遗传易感性和这些结局之间的关联。我们还进行了分层和交互分析，以估计这些结局在遗传风险和 BCS 四分位数中的发生率。结果我们纳入了 368,340 名 UKB 参与者 （中位年龄 58 岁 （四分位距 51-63 岁），46.3% 为男性）。与遗传风险无关，BCS 增加 5 个百分点对应于卒中风险降低（风险比 [HR] 0.70,95% CI 0.68-0.73）、LLD（HR 0.65,95% CI 0.63-0.67）和痴呆（HR 0.82,95% CI 0.78-0.85）。在对这些结局具有高遗传风险的参与者中，所有 3 种结局的发生率都较高。然而，这些增加的风险被 BCS 较高的个体所抵消（每 1,000 人年的发病率为 2.76 vs 1.19，LLD 为 7.34 vs 4.46，以及 3.比较低和高 BCS 时，痴呆为 64 vs 2.05）。讨论 在中风、LLD 和痴呆的不同遗传易感性中，更健康的生活方式行为对大脑健康具有保护作用，证明了遗传风险的非决定性。此外，BCS 的差异充当所有 3 种结果的聚合风险估计器。需要进一步的工作来前瞻性地研究 BCS 作为针对年龄相关脑疾病遗传风险较高的人群的靶向干预措施的效用和性能。