Supplementary materials for: Influence of cognitive reserve on cognitive trajectories: role of brain pathologies

Background and Objectives: Evidence on the association of the 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. Methods: Within the
Rush Memory and Aging Project, 1,697 dementia-free participants (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 (the 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 died and
underwent autopsies to evaluate brain pathologies. Data were analyzed
using linear mixed-effect models. Results: 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 to 0.043), episodic memory (β=0.028, 95%
CI: 0.010 to 0.047) and working memory (β=0.019, 95% CI: 0.005 to 0.033)
during the follow-up. In brain pathological data analysis, the association
of the highest CR with cognitive function changes remained significant
among participants with high Alzheimer's disease pathology or gross
infarcts. Discussion: 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.

背景与研究目的：目前关于认知储备（Cognitive Reserve，CR）与认知轨迹之间关联的研究证据较为有限。本研究旨在探讨纳入脑部病理因素后，认知储备指标对特定领域认知轨迹的影响。

方法：在拉什记忆与衰老项目（Rush Memory and Aging Project）中，共纳入1697名无痴呆受试者（平均年龄79.6岁），随访时长最长达21年。研究人员在基线时评估了涵盖教育水平、生命早期、中年及晚年认知活动，以及晚年社交活动的认知储备指标，并将其按三分位分组（低、中、高三组）。研究每年通过19项测试对整体认知、情景记忆、语义记忆、工作记忆、视空间能力及感知速度进行评估，并据此计算综合得分。随访期间，共有648名受试者去世并接受尸检，以评估其脑部病理情况。本研究采用线性混合效应模型对数据进行分析。

结果：受试者的认知储备指标得分范围为-8.00至5.74（均值：0.00±2.23）。在多因素校正的混合效应模型中，与低认知储备组相比，高认知储备组受试者在随访期间的整体认知（β=0.028，95%置信区间[CI]：0.012~0.043）、情景记忆（β=0.028，95%置信区间[CI]：0.010~0.047）及工作记忆（β=0.019，95%置信区间[CI]：0.005~0.033）衰退速度更慢。在脑部病理数据分析中，在阿尔茨海默病病理程度较高或存在大体梗死的受试者中，高认知储备与认知功能变化的关联仍具有统计学意义。

讨论：即使存在脑部病理改变，较高的认知储备指标仍与更好的整体认知功能、情景记忆及工作记忆保留相关。本研究结果凸显了积累较高认知储备在预防认知衰退中的重要作用。