Characterizing the Behavior Profile of Healthy Cognitive Aging

项目摘要 认知能力下降在老年人中几乎是普遍的，预防认知能力下降是 21世纪最重要的公共卫生挑战。尽管有相当大 在确定老年人认知能力下降的原因方面取得的进展，令人惊讶的是， 健康认知老化的概况。大多数现有的研究， 健康的认知老化研究了没有临床症状的人的认知变化， 痴呆然而，绝大多数没有痴呆症的人来验尸， 有广泛的神经病理学证据的疾病通常已知的原因 老年认知障碍，特别是阿尔茨海默病、脑梗死， 路易体，并排除没有临床痴呆症的人不考虑 神经病理学的积累对认知老化的影响。 此外，大多数老年人在刚出生的几年里表现出认知能力的急剧下降。 在死亡之前，这种现象被称为终端下降，这也有助于 认知老化因此，认知能力下降的很大一部分目前归因于 健康的认知老化可能是由于累积的神经病理学的影响， 和终端下降。我们建议使用创新的统计方法， 描述健康认知老化的特征，定义为与年龄相关的认知 不被常见神经病理学的存在所解释的变化（即， 阿尔茨海默氏病、脑梗塞和路易体疾病）或终末衰退。 拟议的研究将利用独特的纵向认知和 神经病理学数据来自两项正在进行的流行病学研究，宗教 订单研究（P30AG10161），将作为探索性队列，以及Rush 记忆和衰老项目（R01AG17917），将作为确证性队列。 这些研究进行了可比和详细的年度认知评估， 共有二千三百多人，全部同意捐献大脑。年底前 在拟议研究的资助期间，将有超过23，000个认知数据点 可从2，500多人中获得，每年随访长达20年。在 此外，还将提供1 200多人的详细尸检数据。 这些研究的数据将被用来模拟认知变化的轨迹， 功能的积累神经病理和终端下降，以阐明 健康认知老化的轨迹（即，年龄相关的认知变化未考虑在内 通过常见的神经病理学或终端下降）。这项研究提供了一种新颖的， 及时，和潜在的强大的方法来确定健康的认知老化的概况。 了解健康认知老化的轨迹对于识别 可能受益于预防与年龄相关的认知能力下降的干预措施的人 并最终用于识别与成功老化相关的因素。

Project Abstract Cognitive decline is nearly universal in older persons and its prevention is one of the most important public health challenges of the 21st century. Despite considerable progress in identifying the causes of cognitive decline in older persons, surprisingly little is known about the profile of healthy cognitive aging. Most of the available studies of healthy cognitive aging have examined cognitive change in persons without clinical dementia. However, the vast majority of persons without dementia who come to autopsy have extensive neuropathologic evidence of the diseases commonly known to cause cognitive impairment in old age, particularly Alzheimer's disease, cerebral infarcts, and Lewy bodies, and the exclusion of persons without clinical dementia does not account for the effect of accumulating neuropathology on the trajectory of cognitive aging. Moreover, most older persons exhibit a precipitous decline in cognition in the years just prior to death, a phenomenon referred to as terminal decline, and this also contributes to cognitive aging. Thus, a substantial portion of the cognitive decline currently attributed to healthy cognitive aging likely is due to the influence of accumulating neuropathology and terminal decline. We propose to use innovative statistical approaches to characterize the profile of healthy cognitive aging defined as age-related cognitive change not accounted for by the presence of common neuropathologies (i.e., Alzheimer's disease, cerebral infarcts, and the Lewy body diseases) or terminal decline. The proposed study will capitalize on the unique longitudinal cognitive and neuropathologic data available from two ongoing epidemiologic studies, the Religious Orders Study (P30AG10161), which will serve as the exploratory cohort, and the Rush Memory and Aging Project (R01AG17917), which will serve as the confirmatory cohort. These studies perform comparable and detailed annual cognitive evaluations on more than 2,300 persons in total, all of whom have agreed to brain donation. By the end of the funding period of the proposed study, more than 23,000 cognitive data points will be available from more than 2,500 persons with up to 20 years of annual follow-up. In addition, detailed post-mortem data will be available from more than 1,200 persons. Data from these studies will be used to model the trajectory of cognitive change as a function of accumulating neuropathology and terminal decline in order to elucidate the trajectory of healthy cognitive aging (i.e., age-related cognitive change not accounted for by common neuropathologies or terminal decline). The proposed study offers a novel, timely, and potentially powerful approach to identify the profile of healthy cognitive aging. Knowledge of the trajectory of healthy cognitive aging is essential for the identification of persons who might benefit from interventions to prevent age-related cognitive decline and, ultimately, for the identification of factors associated with successful aging.