Characterizing the Behavior Profile of Healthy Cognitive Aging

表征健康认知衰老的行为特征

• 批准号: 7715404
• 负责人: PATRICIA A BOYLE
• 金额: $ 24.6万
• 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/7715404
• 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; 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（由申请人提供）：认知功能减退在老年人中几乎是普遍的，其预防是21世纪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，人们对健康认知老化的概况知之甚少。大多数关于健康认知老化的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来尸检有广泛的神经病理学证据的疾病，通常已知导致认知障碍的老年人，特别是阿尔茨海默氏病，脑梗死，路易体，和排除的人没有临床痴呆症并不能解释累积的神经病理学对认知老化的轨迹的影响。此外，大多数老年人在死亡前几年的认知能力急剧下降，这种现象被称为终端衰退，这也有助于认知老化。因此，目前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神经病理学和终末衰退的影响。我们建议使用创新的统计方法来表征健康认知老化的特征，健康认知老化定义为与年龄相关的认知变化，而不是由常见神经病理学的存在（即，阿尔茨海默氏病、脑梗塞和路易体疾病）或终末衰退。拟议的研究将利用两项正在进行的流行病学研究中的独特纵向认知和神经病理学数据，即宗教秩序研究（P30 AG 10161）（将作为探索性队列）和拉什记忆和衰老项目（R 01 AG 17917）（将作为验证性队列）。这些研究对总共2,300多人进行了可比和详细的年度认知评估，所有这些人都同意捐赠大脑。到拟议研究的资助期结束时，将从2,500多人中获得23,000多个认知数据点，并进行长达20年的年度随访。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用于模拟认知变化的轨迹作为累积神经病理学和终末衰退的函数，以阐明健康认知老化的轨迹（即，与年龄相关的认知变化不被常见的神经病理学或终末衰退所解释）。这项拟议的研究提供了一种新颖，及时和潜在的强大方法来确定健康认知老化的概况。健康认知老化的轨迹的知识是必不可少的人谁可能受益于干预措施，以防止与年龄相关的认知能力下降，并最终确定与成功的老龄化相关的因素的识别。 公共卫生相关性：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世纪世纪最重要的公共卫生挑战之一。首先，健康认知老化的概况的知识将允许鉴定表现出病理性认知老化的最早迹象的人，这些人最有可能从可用的疗法和疾病调节剂中受益。第二，拟议的研究将阐明常见神经病理学在多大程度上是与年龄有关的认知变化的基础，并将直接说明与通常已知会导致老年认知障碍的疾病有关的公共卫生负担;如果常见的神经病变是老年人认知变化的主要原因，那么这些数据将表明，这些疾病造成的公共卫生负担比目前认识到的要大，而且更多的人，包括那些没有明显痴呆症的人，最终可能受益于针对认知障碍和痴呆症开发的有效治疗和预防策略。