Characterizing the Behavior Profile of Healthy Cognitive Aging

表征健康认知衰老的行为特征

• 批准号: 7910656
• 负责人: PATRICIA A BOYLE
• 金额: $ 24.35万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-15 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7910656
• 关键词: Accounting; Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; Autopsy; Behavior; Brain; Cerebral Infarction; Cerebrum; Cessation of life; Clinical; Cognition; Cognitive; Cognitive aging; Complement; Data; Data Set; Dementia; Disease; Elderly; Epidemiologic Studies; Epidemiology; Episodic memory; Evaluation; Exclusion; Exhibits; Funding; Goals; Impaired cognition; Infarction; Intervention; Knowledge; Lewy Bodies; Lewy Body Disease; Measurable; Measures; Memory; Modeling; Participant; Pathologic; Pathologic Processes; Pathology; Persons; Prevention; Prevention strategy; Public Health; Religion and Spirituality; Semantic memory; Short-Term Memory; Speed; Terminal Disease; Testing; Time; Visuospatial; age related cognitive change; base; cognitive change; cognitive function; cohort; effective therapy; follow-up; innovation; neuroimaging; neuropathology; novel; prevent; public health relevance

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.

描述(申请人提供)：认知衰退在老年人中几乎是普遍存在的，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衰退的原因方面取得了相当大的进展，但令人惊讶的是，人们对健康认知老化的概况知之甚少。大多数现有的关于健康认知老化的研究都考察了没有临床痴呆症的人的认知变化。然而，绝大多数来尸检的非痴呆者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、脑梗塞和路易体，而排除没有临床痴呆症的人并不能解释累积的神经病理对认知老化轨迹的影响。此外，大多数老年人在去世前几年表现出认知能力的急剧下降，这一现象被称为终末期衰退，这也是认知老化的原因之一。因此，目前被归因于健康认知老化的认知衰退的很大一部分可能是由于累积的神经病理和终末性衰退的影响。我们建议使用创新的统计方法来描述健康认知老化的特征，健康认知老化被定义为与年龄相关的认知变化，而不是常见神经病理(即阿尔茨海默病、脑梗塞和路易体疾病)或终末期衰退的存在。这项拟议的研究将利用从两项正在进行的流行病学研究中获得的独特的纵向认知和神经病理学数据，宗教教派研究(P30AG10161)将作为探索性队列，而快速记忆和老龄化项目(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，所有人都同意捐赠大脑。到拟议研究的资助期结束时，将从2500多人那里获得23000多个认知数据点，并进行长达20年的年度跟踪。此外，还将提供1200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，作为累积神经病理和终末性衰退的函数，以阐明健康认知老化的轨迹(即，与年龄相关的认知变化不能被常见的神经病理或终末性衰退所解释)。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。了解健康认知老化的轨迹对于确定谁可能受益于预防与年龄相关的认知衰退的干预措施至关重要，并最终确定与成功老龄化相关的因素。 公共卫生相关性：认知能力下降在老年人中几乎普遍存在，其预防是21世纪最重要的公共卫生挑战之一。首先，了解健康认知老化的概况将允许识别出表现出病理性认知老化最早迹象的人，这些人最有可能从现有的治疗方法和疾病改良剂中受益。第二，拟议的研究将阐明常见神经病理在多大程度上导致与年龄相关的认知变化，并将直接告知与常见的导致老年人认知障碍的疾病相关的公共健康负担；如果常见神经病理导致老年人的认知变化，那么这些数据将表明，这些疾病造成的公共健康负担比目前认识到的更大，更多的人，包括那些没有明显痴呆的人，最终可能受益于为认知障碍和痴呆症制定的有效治疗和预防策略。