Evidence on the association of cognitive reserve (CR) with the cognitive trajectories is limited. We aimed to examine the influence of CR indicator on domain-specific cognitive trajectories taking brain pathologies into account.

Within the Rush Memory and Aging Project, 1,697 participants without dementia (mean age 79.6 years) were followed up to 21 years. CR indicator encompassing education, early-life, mid-life, and late-life cognitive activities and late-life social activity was ascertained at baseline and categorized as tertiles (lowest, middle, and highest). Global cognition, episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed were assessed annually with 19 tests, from which composite scores were derived. During the follow-up, 648 participants died and underwent autopsies to evaluate brain pathologies. Data were analyzed using linear mixed-effect models.

Among the participants, the score of the CR indicator ranged from –8.00 to 5.74 (mean 0.00 ± 2.23). In multi-adjusted mixed-effect models, compared to the lowest CR, the highest was related to a slower decline in global cognition (β = 0.028, 95% confidence interval [CI] 0.012–0.043), episodic memory (β = 0.028, 95% CI 0.010–0.047), and working memory (β = 0.019, 95% CI 0.005–0.033) during the follow-up. In brain pathologic data analysis, the association of the highest CR with cognitive function changes remained significant among participants with high Alzheimer disease pathology or gross infarcts.

High CR indicator is associated with preserved global cognitive function, episodic memory, and working memory, even in the presence of brain pathologies. Our findings highlight the important role of high CR accumulation in the prevention of cognitive decline.

关于认知储备（CR）与认知轨迹之间关系的证据有限。我们的目的是研究 CR 指标对特定领域认知轨迹的影响，同时考虑到大脑病理学。

在 Rush Memory and Aging Project 中，1,697 名没有痴呆症的参与者（平均年龄 79.6 岁）接受了长达 21 年的随访。CR 指标涵盖教育、早年、中年和晚年认知活动以及晚年社交活动，在基线时确定并分为三分位数（最低、中间和最高）。每年通过 19 项测试评估全局认知、情景记忆、语义记忆、工作记忆、视觉空间能力和感知速度，并从中得出综合分数。在随访期间，648 名参与者死亡并接受尸检以评估脑部病理情况。使用线性混合效应模型分析数据。

参与者中，CR 指标的得分范围为 –8.00 至 5.74（平均值 0.00 ± 2.23）。在多重调整混合效应模型中，与最低 CR 相比，最高 CR 与整体认知（β = 0.028，95% 置信区间 [CI] 0.012–0.043）、情景记忆（β = 0.028， 95% CI 0.010–0.047) 和随访期间的工作记忆 (β = 0.019, 95% CI 0.005–0.033)。在脑病理数据分析中，在患有高度阿尔茨海默病病理或严重梗塞的参与者中，最高 CR 与认知功能变化之间的关联仍然显着。

即使存在大脑病变，高 CR 指标也与保留的整体认知功能、情景记忆和工作记忆相关。我们的研究结果强调了高 CR 积累在预防认知能力下降中的重要作用。