Department of Neurology, Memory and Aging Center, University of California, San Francisco, CA, USA.
Department of Neurology, Memory and Aging Center, University of California, San Francisco, CA, USA.
Neurobiol Aging. 2019 May;77:13-19. doi: 10.1016/j.neurobiolaging.2019.01.007. Epub 2019 Jan 24.
Age-related cognitive decline is a public health problem but highly diverse and difficult to predict. We captured nonoverlapping cognitive phenotypes in high-functioning adults and identified baseline factors differentiating trajectories. Three hundred fourteen functionally normal adults (M = 69 y) completed 2+ visits. Participants with sample-based longitudinal slopes in memory or processing speed less than -1 SD were classified as "declining" on that measure; 29 and 50 individuals had slopes less than -1 SD on processing speed or memory, respectively; 2.5% met criteria for both, who were excluded. At baseline, speed decliners demonstrated greater age, inflammation, and cognitive complaints compared with speed-stable adults; memory decliners were more likely to be male and had lower depressive symptoms, gray matter volumes, and white matter hyperintensities compared with memory-stable adults. Baseline speed, TNFα, and cognitive complaints accurately classified 96.3% of future speed decliners; baseline memory, sex, precuneal volume, and white matter hyperintensities accurately classified 88.5% of future memory decliners. There are discrete cognitive aging phenotypes reflecting nonoverlapping vulnerabilities in high-functioning adults. Early markers can predict cognition even within the "normal" spectrum and underscore therapeutic targets.
年龄相关性认知衰退是一个公共卫生问题，但高度多样化且难以预测。我们在高功能成年人中捕捉到不重叠的认知表型，并确定了区分轨迹的基线因素。314 名功能正常的成年人（M=69 岁）完成了 2 次以上的访问。以记忆或处理速度的样本为基础的纵向斜率小于-1 SD 的参与者在该指标上被归类为“下降”；分别有 29 人和 50 人在处理速度或记忆方面的斜率小于-1 SD；符合两个标准的有 2.5%，被排除在外。在基线时，与处理速度稳定的成年人相比，速度下降者的年龄更大、炎症更多、认知问题更多；与记忆稳定的成年人相比，记忆下降者更有可能是男性，抑郁症状、灰质体积和脑白质高信号更少。基线速度、TNFα 和认知主诉准确地将 96.3%的未来速度下降者分类；基线记忆、性别、楔前叶体积和脑白质高信号准确地将 88.5%的未来记忆下降者分类。存在离散的认知老化表型，反映了高功能成年人中不重叠的脆弱性。早期标志物甚至可以在“正常”范围内预测认知，并强调治疗靶点。
