Characterizing the Behavior Profile of Healthy Cognitive Aging

摘要 预防晚年认知能力下降是最重要的公共卫生挑战之一， 确定健康认知老化的概况是一个重要步骤。拟议的研究将继续进行， 一项非常成功的研究计划，改变了该领域对健康认知衰老的理解 （R01AG34374）。我们将健康的认知老化概念化为晚年的认知变化， 已知的病理过程（例如，AD/ADRD病理学），我们的研究利用了 来自宗教秩序研究和匆忙记忆与衰老的纵向认知和病理数据 项目（ROSMAP）。其中心思想是，我们可以精确地描述病理性认知老化， 将病理指标与纵向认知轨迹相关联，然后识别健康的认知老化（即，残余 改变）。在以前的周期中，我们报告：a）常见的AD/ADRD神经病理学占大多数 先前归因于健康认知老化的下降，但低于总体下降变化的一半; B） 非线性的终末变化代表了一个单独的病理过程，是衰退的主要驱动力; c） AD/ADRD神经病理学差异性地影响特定认知系统的轨迹;以及d）我们的新研究 开发的“认知年龄”指标是不良认知结果的可靠预后指标。整体 建议继续的目标是进一步阐明健康认知老化的概况， 将我们在死者身上的工作转化为活着的人， 认知老化拟议的研究将纳入新的神经病理学指标，神经影像学， AD和神经退行性变的有前途的血液生物标志物，并应用高度创新的统计方法， 准确识别健康认知老化的特征。在先前工作的基础上，我们将首先确定健康的 认知老化的尸检人员与详细的病理资料。重要的是，我们将扩展这个 接近活人。最后，我们将整合新的生物标志物和死前神经成像数据， 我们的认知年龄指标，以制定预测MCI和阿尔茨海默氏痴呆的标准， 在一个独立的数据集中验证它们，该数据集来自一个基于人口的样本，芝加哥健康和 老龄化项目。因此，拟议的研究提供了一个创新的方法来解决一个基本的， 认知老化研究的长期挑战。这项工作也将有利于早期和准确 识别认知障碍高危人群，这是老龄化研究的当务之急。

ABSTRACT Prevention of late life cognitive decline ranks among the most important public health challenges, and identification of the profile of healthy cognitive aging is an essential step. The proposed study will continue a highly successful program of research that has transformed the field’s understanding of healthy cognitive aging (R01AG34374). We conceptualize healthy cognitive aging as the late life cognitive change that is not due to known pathologic processes (e.g., AD/ADRD pathologies), and our research capitalizes on the detailed longitudinal cognitive and pathologic data from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP). The central idea is that we can precisely characterize pathologic cognitive aging by linking pathologic indices to longitudinal cognitive trajectories and then identify healthy cognitive aging (i.e., residual change). In prior cycles, we reported that: a) common AD/ADRD neuropathologies account for much of the decline previously attributed to healthy cognitive aging but less than half of the variation in decline overall; b) nonlinear, terminal change represents a separate pathologic process and a major driver of decline; c) AD/ADRD neuropathologies differentially impact trajectories of specific cognitive systems; and d) our newly developed “cognitive age” metric is a robust prognostic indicator of adverse cognitive outcomes. The overall goal of the proposed continuation is to further elucidate the profile of healthy cognitive aging and translate our work in decedents into the living to prospectively distinguish healthy from pathologic cognitive aging. The proposed study will incorporate new neuropathologic indices, neuroimaging, and promising blood biomarkers of AD and neurodegeneration and apply a highly innovative statistical approach to precisely identify the profile of healthy cognitive aging. Building on prior work, we will first identify healthy cognitive aging among autopsied persons with detailed pathologic data. Importantly, we will then extend this approach to living persons. Finally, we will integrate new biomarker and ante-mortem neuroimaging data with our cognitive age metric to develop criteria for prediction of incident MCI and Alzheimer’s dementia and validate them in an independent dataset from a biracial, population-based sample, the Chicago Health and Aging Project (CHAP). Thus, the proposed study offers an innovative approach to address a fundamental and longstanding challenge in cognitive aging research. This work also will facilitate early and accurate identification of individuals at high risk of developing cognitive impairment, an urgent priority in aging research.