Characterizing the Behavior Profile of Healthy Cognitive Aging

描述（由申请人提供）：认知能力下降在老年人中几乎是普遍的，其预防是21世纪最重要的公共卫生挑战之一。尽管在确定老年人认知能力下降的原因方面取得了相当大的进展，但令人惊讶的是，人们对健康认知衰老的概况知之甚少。大多数关于健康认知衰老的现有研究都检查了没有临床痴呆的人的认知变化。然而，绝大多数没有痴呆症的人在尸检时都有广泛的神经病理学证据，证明了通常会导致老年人认知障碍的疾病，特别是阿尔茨海默病、脑梗死和路易体，没有临床痴呆症的人被排除在外并不能解释神经病理学对认知衰老轨迹的影响。此外，大多数老年人在死亡前几年的认知能力急剧下降，这种现象被称为“终末衰退”，这也会导致认知老化。因此，目前归因于健康认知衰老的认知能力下降的很大一部分可能是由于神经病理学积累和终末期衰退的影响。我们建议使用创新的统计方法来描述健康认知衰老的特征，定义为与年龄相关的认知变化，而不是由常见神经病变（如阿尔茨海默病、脑梗死和路易体病）或终末期衰退所引起的。拟议的研究将利用来自两项正在进行的流行病学研究的独特的纵向认知和神经病理学数据，宗教秩序研究（P30AG10161）将作为探索性队列，而拉什记忆和衰老项目（R01AG17917）将作为验证性队列。这些研究对总共2300多人进行了可比较和详细的年度认知评估，他们都同意捐献大脑。到拟议研究的资助期结束时，将有超过23,000个认知数据点，来自超过2,500人，每年随访长达20年。此外，还将提供1 200多人的详细尸检数据。来自这些研究的数据将被用于模拟认知变化的轨迹，作为神经病理积累和终末期衰退的功能，以阐明健康认知衰老的轨迹（即，与年龄相关的认知变化不被常见的神经病理或终末期衰退所解释）。提出的研究提供了一种新颖、及时、潜在的强有力的方法来确定健康认知衰老的概况。了解健康认知衰老的轨迹对于确定哪些人可能受益于预防与年龄有关的认知衰退的干预措施，并最终确定与成功衰老相关的因素至关重要。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Cognitive decline is nearly universal in older persons and its prevention is one of the most important public health challenges of the 21st century. First, knowledge of the profile of healthy cognitive aging will allow for identification of persons exhibiting the earliest signs of pathologic cognitive aging who are most likely to benefit from the available therapies and disease modifying agents as they become available. Second, the proposed study will elucidate the extent to which common neuropathologies underlie age-related cognitive change and will directly inform on the public health burden associated with the diseases commonly known to cause cognitive impairment in old age; if common neuropathologies account for most of cognitive change seen in older persons, then these data would suggest that the public health burden posed by these diseases is greater than currently recognized and that a much larger group of persons, including those without overt dementia, ultimately may benefit from effective treatment and prevention strategies developed for cognitive impairment and dementia.