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存在的，而预防认知能力下降是 21世纪最重要的公共卫生挑战。尽管有相当大的 在确定老年人认知衰退原因方面取得的进展令人惊讶地微乎其微 已经知道了健康认知老化的概况。大多数现有的研究都是关于 健康的认知老化检查了没有临床症状的人的认知变化 痴呆症。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表明这些疾病通常会导致 老年人的认知障碍，特别是阿尔茨海默病、脑梗塞和 刘易体，排除无临床痴呆症的人不占 研究神经病理堆积对认知衰老轨迹的影响。 此外，大多数老年人的认知能力在过去的几年里急剧下降。 在死亡之前，一种被称为末期衰退的现象，这也有助于 认知老化。因此，目前认知能力下降的很大一部分原因是 对健康认知老化的影响可能是由于神经病理的累积 和末期衰退。我们建议使用创新的统计方法来 描述健康认知老化的特征，定义为与年龄相关的认知 未由常见神经病理的存在解释的变化(即， 阿尔茨海默病、脑梗塞和路易体疾病)或晚期衰退。 拟议的研究将利用独特的纵向认知和 来自两项正在进行的流行病学研究的神经病理学数据，宗教 Orders Study(P30AG10161)，将作为探索队列，以及Rush 记忆与衰老项目(R01AG17917)，将作为验证性队列。 这些研究对更多的人进行可比较和详细的年度认知评估 总共有2300多人，他们都同意捐赠大脑。到年底的时候 在拟议研究的资助期内，将有超过23,000个认知数据点 超过2,500人提供，每年最多跟踪20年。在……里面 此外，将有1200多人提供详细的尸检数据。 这些研究的数据将被用来将认知变化的轨迹建模为 积累神经病理和终末期衰退的作用以阐明 健康认知老化的轨迹(即，不考虑与年龄相关的认知变化 由常见的神经病理或终末期衰退引起)。这项拟议的研究提供了一种新的、 及时的，潜在的强有力的方法来确定健康认知老化的概况。 对健康认知老化轨迹的了解对于识别 可能从预防年龄相关性认知衰退的干预措施中受益的人 最终，用于识别与成功衰老相关的因素。

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.