Characterizing the Behavior Profile of Healthy Cognitive Aging

 描述（由申请人提供）：预防老年认知能力下降是最重要的公共卫生挑战之一。识别健康的认知老化一直被认为是一个重要的步骤。然而，尽管经过数十年的研究，健康认知老化的概况仍然未知，因为损害认知的病理过程通常存在，但在健康认知老化的研究中没有考虑到。大多数现有的研究都检查了非痴呆症患者的认知变化。然而，许多没有认知障碍的人来尸检时有广泛的神经病理学证据表明，已知常见疾病会导致老年认知障碍（即，AD、CVD和LBD）。此外，最近的数据表明，其他神经病理学在没有痴呆的人中也很常见（例如，TDP-43、海马硬化、白色物质疾病）。此外，大多数老年人在死亡前几年表现出认知能力的急剧下降（即终端下降）。终末衰退代表了一个单独的病理过程，在健康认知老化的研究中还没有考虑到。我们提出了一个新的概念，健康的认知老化的认知变化不占病理过程已知损害认知在老年（即，神经病理学和终末认知衰退）。拟议继续的总体目标是确定健康认知老化的概况， 将其与病理性和晚期认知衰退区分开来。我们的研究利用了两项正在进行的老龄化研究的数据，即宗教秩序研究和记忆与衰老项目，这些研究收集了识别健康认知衰老所需的独特纵向认知和详细的死后数据。我们将首先量化由于神经病理性和终末认知衰退（即，病理性认知老化）。然后，我们将识别健康的认知老化（即，残余的认知变化）。为此，拟议的研究将采用多模式方法来量化几个新的病理指标（即，TDP- 43的神经病理学指标、海马硬化、白色疾病和来自神经成像的脑完整性的多个指标），并使用创新性分析来检查它们对认知轨迹的贡献，超过AD、CVD和LBD。这项研究提供了一个难得的机会，以确定健康的认知老化的概况，并将其与神经病理和终端认知衰退区分开来。我们不知道其他的研究，量化基本上所有的病理过程，已知损害认知在老年人将在这里做，其中类似的分析可以进行。这项研究提供了一种创新的方法来解决认知老化研究中的一个根本和长期挑战。了解健康认知老化的轨迹对于早期识别将从有效干预中受益最多的人以及最终预防老年认知衰退至关重要。

 DESCRIPTION (provided by applicant): Prevention of cognitive decline in old age ranks among the most important public health challenges. Identification of healthy cognitive aging has long been considered an essential step. However, despite decades of research, the profile of healthy cognitive aging remains unknown because pathologic processes that impair cognition often are present but not accounted for in studies of healthy cognitive aging. Most of the available studies have examined cognitive change in persons without dementia. However, many persons without cognitive impairment who come to autopsy have extensive neuropathologic evidence of common diseases known to cause cognitive impairment in old age (i.e., AD, CVD, and LBD). Moreover, recent data suggest that additional neuropathologies also are common in persons without dementia (e.g., TDP-43, hippocampal sclerosis, white matter disease). Further, most older persons exhibit a precipitous decline in cognition in the years just prior to death (i.e, terminal decline). Terminal decline represents a separate pathologic process that has not been accounted for in studies of healty cognitive aging. We propose a novel conceptualization of healthy cognitive aging as the cognitive change not accounted for by pathologic processes known to impair cognition in old age (i.e., neuropathologies and terminal cognitive decline). The overall goal of the proposed continuation is to identify the profile of healthy cognitive aging and distinguish it from pathologic and terminal cognitive decline. Our research capitalizes on data from two ongoing studies of aging, the Religious Orders Study and the Memory and Aging Project, that collect the unique longitudinal cognitive and detailed post-mortem data required to identify healthy cognitive aging. We will first quantify the cognitive change due to neuropathologic and terminal cognitive decline (i.e., pathologic cognitive aging). Then, we will identify healthy cognitive aging (i.e., the residual cognitive change). Toward this end, the proposed study will employ a multimodal approach to quantify several new pathologic indices (i.e., neuropathologic indices of TDP- 43, hippocampal sclerosis, white matter disease, and multiple indices of brain integrity derived from neuroimaging) and use innovative analyses to examine their contribution to cognitive trajectories, above and beyond AD, CVD, and LBD. The proposed study offers a rare opportunity to identify the profile of healthy cognitive aging and distinguish it from neuropathologic and terminal cognitive decline. We are not aware of other studies that quantify essentially all of the pathologic processes known to impair cognition in old age as will be done here and in which similar analyses could be performed. The proposed study offers an innovative approach to address a fundamental and longstanding challenge in cognitive aging research. Knowledge of the trajectory of healthy cognitive aging is essential for the early identification of persons who will benefit most from effective intervention and, ultimately, for th prevention of cognitive decline in old age.