ImportanceA healthy lifestyle is associated with better cognitive functioning in older adults, but whether this association is independent of the accumulation of dementia-related pathologies in the brain is uncertain.ObjectiveTo determine the role of postmortem brain pathology, including β-amyloid load, phosphorylated tau tangles, cerebrovascular pathology, and other brain pathologies, in the association between lifestyle and cognition proximate to death.Design, Setting, and ParticipantsThis cohort study used data from the Rush Memory and Aging Project, a longitudinal clinical-pathologic study with autopsy data from 1997 to 2022 and up to 24 years of follow-up. Participants included 754 deceased individuals with data on lifestyle factors, cognitive testing proximate to death, and a complete neuropathologic evaluation at the time of these analyses. Data were analyzed from January 2023 to June 2023.ExposuresA healthy lifestyle score was developed based on self-reported factors, including noncurrent smoking, at least 150 minutes of physical activity per week, limiting alcohol consumption, a Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet score higher than 7.5, and a late-life cognitive activity score higher than 3.2. The lifestyle score ranges from 0 to 5, with higher scores reflecting a healthier lifestyle.Main Outcomes and MeasuresThe global cognitive score was derived from a battery of nineteen standardized tests. Brain pathology measures included β-amyloid load, phosphorylated tau tangles, global Alzheimer disease pathology, vascular brain pathologies, Lewy body, hippocampal sclerosis, and TAR DNA-binding protein 43.ResultsOf 586 included decedents, 415 (70.8%) were female, 171 (29.2%) were male, and the mean (SD) age at death was 90.9 (6.0) years. Higher lifestyle score was associated with better global cognitive functioning proximate to death. In the multivariable-adjusted model, a 1-point increase in lifestyle score was associated with 0.216 (SE = 0.036, P < .001) units higher in global cognitive scores. Neither the strength nor the significance of the association changed substantially when common dementia-related brain pathologies were included in the multivariable-adjusted models. The β estimate after controlling for the β-amyloid load was 0.191 (SE = 0.035; P < .001). A higher lifestyle score was associated with lower β-amyloid load in the brain (β = −0.120; SE = 0.041; P = .003), and 11.6% of the lifestyle-cognition association was estimated through β-amyloid load.Conclusions and RelevanceThis study found that in older adults, a healthy lifestyle may provide a cognitive reserve to maintain cognitive abilities independently of common neuropathologies of dementia.

中文翻译：

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患有常见痴呆症神经病理学的老年人的健康生活方式和认知

重要性健康的生活方式与老年人更好的认知功能相关，但这种关联是否独立于大脑中痴呆相关病理的积累尚不确定。目的确定死后脑病理的作用，包括 β-淀粉样蛋白负荷、磷酸化 tau 蛋白缠结、脑血管病理学和其他脑部病理学，在生活方式和临近死亡的认知之间的关联。设计、设置和参与者这项队列研究使用了来自 Rush Memory and Aging Project 的数据，该项目是一项纵向临床病理研究，使用了 1997 年的尸检数据到 2022 年以及长达 24 年的后续行动。参与者包括 754 名死者，他们提供了生活方式因素、临终认知测试以及分析时完整的神经病理学评估的数据。数据分析时间为 2023 年 1 月至 2023 年 6 月。暴露健康生活方式评分是根据自我报告的因素制定的，包括非当前吸烟、每周至少 150 分钟的体力活动、限制饮酒、针对神经退行性延迟的地中海 DASH 干预措施（ MIND）饮食评分高于 7.5，晚年认知活动评分高于 3.2。生活方式得分范围为 0 到 5，得分越高，生活方式越健康。 主要结果和衡量标准 全球认知得分源自一系列 19 项标准化测试。脑病理学测量包括 β-淀粉样蛋白负荷、磷酸化 tau 蛋白缠结、整体阿尔茨海默病病理学、血管脑病理学、路易体、海马硬化和 TAR DNA 结合蛋白 43。结果 586 名死者中，415 名 (70.8%) 为女性，171 名(29.2%) 为男性，平均 (SD) 死亡年龄为 90.9 (6.0) 岁。较高的生活方式得分与临终时较好的整体认知功能相关。在多变量调整模型中，生活方式评分每增加 1 分，与 0.216 相关（SE = 0.036，磷< .001) 整体认知得分更高。当多变量调整模型中包含常见的痴呆相关脑部病理时，这种关联的强度和显着性都没有发生实质性变化。控制 β-淀粉样蛋白负荷后的 β 估计值为 0.191（SE = 0.035；磷< .001）。较高的生活方式评分与大脑中较低的 β-淀粉样蛋白负荷相关（β = -0.120；SE = 0.041；磷= .003），并且 11.6% 的生活方式与认知关联是通过 β-淀粉样蛋白负荷估计的。结论和相关性这项研究发现，在老年人中，健康的生活方式可以提供认知储备，以维持独立于常见痴呆症神经病理学的认知能力。