McDermott Kirstie L, McFall G Peggy, Andrews Shea J, Anstey Kaarin J, Dixon Roger A
Neuroscience and Mental Health Institute.
Department of Psychology, University of Alberta, Edmonton, Canada.
J Gerontol B Psychol Sci Soc Sci. 2017 Oct 1;72(6):937-946. doi: 10.1093/geronb/gbw161.
Apolipoprotein E (APOE) ɛ4 and Clusterin (CLU) C alleles are risk factors for Alzheimer's disease (AD) and episodic memory (EM) decline. Memory resilience occurs when genetically at-risk adults perform at high and sustained levels. We investigated whether (a) memory resilience to AD genetic risk is predicted by biological and other risk markers and (b) the prediction profiles vary by sex and AD risk variant.
Using a longitudinal sample of nondemented adults (n = 642, aged 53-95) we focused on memory resilience (over 9 years) to 2 AD risk variants (APOE, CLU). Growth mixture models classified resilience. Random forest analysis, stratified by sex, tested the predictive importance of 22 nongenetic risk factors from 5 domains (n = 24-112).
For both sexes, younger age, higher education, stronger grip, and everyday novel cognitive activity predicted memory resilience. For women, 9 factors from functional, health, mobility, and lifestyle domains were also predictive. For men, only fewer depressive symptoms was an additional important predictor. The prediction profiles were similar for APOE and CLU.
Although several factors predicted resilience in both sexes, a greater number applied only to women. Sex-specific mechanisms and intervention targets are implied.
载脂蛋白E（APOE）ε4和簇集蛋白（CLU）C等位基因是阿尔茨海默病（AD）和情景记忆（EM）衰退的风险因素。当有遗传风险的成年人保持高水平且持续的表现时，就会出现记忆恢复力。我们研究了（a）生物和其他风险标志物是否能预测对AD遗传风险的记忆恢复力，以及（b）预测模式是否因性别和AD风险变异而有所不同。
我们使用了一个非痴呆成年人的纵向样本（n = 642，年龄53 - 95岁），重点关注对两种AD风险变异（APOE、CLU）的记忆恢复力（超过9年）。生长混合模型对恢复力进行分类。随机森林分析按性别分层，测试了来自5个领域的22个非遗传风险因素的预测重要性（n = 24 - 112）。
对于男女两性，年龄较小、教育程度较高、握力较强和日常新颖的认知活动可预测记忆恢复力。对于女性，功能、健康、活动能力和生活方式领域的9个因素也具有预测性。对于男性，只有较少的抑郁症状是另一个重要的预测因素。APOE和CLU的预测模式相似。
虽然有几个因素可预测男女两性的恢复力，但更多因素仅适用于女性。这意味着存在性别特异性机制和干预靶点。
