Predicting cognitive resilience from midlife lifestyle and multi-modal MRI: A 30-year prospective cohort study

BackgroundThere is significant heterogeneity in the clinical expression of structural brain abnormalities, including Alzheimer’s disease biomarkers. Some individuals preserve their memory despite the presence of risk factors or pathological brain changes, indicating resilience. We aimed to test whether resilient individuals could be distinguished from those who develop cognitive impairment, using sociodemographic variables and neuroimaging.MethodsWe included 550 older adults participating in the Whitehall II study with longitudinal data, cognitive test results, and multi-modal MRI. Hippocampal atrophy was defined as Scheltens Scores >0. Resilient individuals (n = 184) were defined by high cognitive performance despite hippocampal atrophy (HA). Non-resilient participants (n = 133) were defined by low cognitive performance (≥1.5 standard deviations (S.D.) below the group mean) in the presence of HA. Dynamic and static exposures were evaluated for their ability to predict later resilience status using multivariable logistic regression. In a brain-wide analysis we tested for group differences in the integrity of white matter (structural connectivity) and resting-state networks (functional connectivity).FindingsYounger age (OR: 0.87, 95% CI: 0.83 to 0.92, pConclusionsResilient individuals could be distinguished from those who developed impairments on the basis of sociodemographic characteristics, brain structural and functional connectivity, but not midlife lifestyles. There was a synergistic deleterious effect of hippocampal atrophy and poor white matter integrity on cognitive performance. Exploiting and supporting neural correlates of resilience could offer a fresh approach to postpone or avoid the appearance of clinical symptoms.

研究背景：包括阿尔茨海默病生物标志物（Alzheimer’s disease biomarkers）在内的脑结构异常，其临床表型存在显著异质性。部分个体即便存在危险因素或脑部病理改变，仍能维持记忆力，该现象体现了脑认知韧性。本研究旨在利用社会人口学变量与神经影像学数据，区分认知韧性个体与出现认知障碍的个体。
研究方法：本研究纳入了参与白厅II队列研究（Whitehall II study）的550名老年受试者，所有受试者均具备纵向随访数据、认知测试结果及多模态磁共振成像（multi-modal MRI）数据。海马萎缩（hippocampal atrophy）定义为Scheltens评分>0。认知韧性个体（n=184）的判定标准为：存在海马萎缩（HA）但认知功能仍保持高水平。非韧性受试者（n=133）的判定标准为：存在海马萎缩且认知功能评分低于群体均值≥1.5个标准差（standard deviations, S.D.）。本研究采用多变量logistic回归分析，评估动态与静态暴露因素对后续韧性状态的预测能力。在全脑分析中，我们对比了两组受试者的白质完整性（结构连接性，structural connectivity）与静息态网络（功能连接性，functional connectivity）的组间差异。
研究结果：年龄更轻（比值比OR：0.87，95%置信区间CI：0.83~0.92，p
研究结论：可通过社会人口学特征、脑结构与功能连接性区分认知韧性个体与出现认知障碍的个体，但中年生活方式无法作为区分依据。海马萎缩与白质完整性受损对认知功能存在协同损害作用。靶向并调控与认知韧性相关的神经机制，或可为延缓甚至避免临床症状出现提供全新的干预思路。