Characterizing the Behavior Profile of Healthy Cognitive Aging

摘要 预防老年认知能力下降是最重要的公共卫生挑战之一， 识别健康认知老化的特征是至关重要的一步。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老化的理解 (R01AG34374)。我们将健康的认知老化概念化为晚年的认知变化，这种变化不是由于 已知的病理过程(例如，AD/ADRD病理)，我们的研究利用了详细的 来自宗教秩序研究和快速记忆与衰老的纵向认知和病理数据 项目(ROSMAP)。其中心思想是，我们可以通过关联准确地描述病理性认知老化 对纵向认知轨迹的病理指标，然后识别健康的认知老化(即残留 更改)。在以前的周期中，我们报告：a)常见的AD/ADRD神经病理导致很大程度上 下降以前归因于健康的认知老化，但总体下降的变化不到一半；b) 非线性、终末期改变是一个单独的病理过程，是下降的主要驱动因素；c) AD/ADRD神经病理对特定认知系统的轨迹有不同的影响；以及d)我们新的 已开发的“认知年龄”指标是预测不良认知结果的有力指标。整体而言 提议继续的目标是进一步阐明健康的认知老化和 将我们在死者身上的工作转化为活着的人，以期区分健康和病理 认知老化。这项拟议的研究将纳入新的神经病理指标、神经成像和 AD和神经退行性变的有前景的血液生物标记物，并应用高度创新的统计方法 准确识别健康认知老化的概况。在之前工作的基础上，我们将首先确定健康的 有详细病理数据的尸检者中的认知老化。重要的是，我们将延长这一期限 接近活着的人。最后，我们将把新的生物标记物和死前神经成像数据与 我们的认知年龄指标，以制定预测MCI和阿尔茨海默氏症的标准，以及 在一个以人口为基础的双族样本的独立数据集中验证它们，芝加哥健康和 老龄化项目(CHAP)。因此，拟议的研究提供了一种创新的方法，以解决基本和 认知老化研究中的长期挑战。这项工作也将有利于及早准确 识别患有认知障碍的高危个体，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.