Neuropathologic substrates for motor and cognitive impairment in three existing cohort studies of Alzheimer's disease and related dementias

摘要/摘要 这项拟议的工作将调查晚年认知和运动障碍的病因。 阿尔茨海默病，密切相关的脑血管和神经退行性疾病，脑老化，以及他们的 三个现有队列中共同出现的常见模式：檀香山-亚洲老龄化研究，修女研究， 以及90年代的研究。我们的重点将是客观的、纵向的运动功能测量之间的关系 和认知--最后一次获得的是濒临死亡的--以及一套明确的神经病理基础 在尸检中被确认。将使用以下提供的现有资源进行并行和合并分析 这三项基于人群的大型纵向研究由参与者组成，具有明显的不同 性别、年龄和种族。我们将利用这些现有的大量资源来检验这一假设 随着年龄的增长而出现的认知和运动障碍是一种综合征，部分起源于 重叠的混合疾病，在一定程度上因年龄、性别和种族的不同而不同，这可能是 根据他们的神经病理特征，在当前时间是最好的。这将允许识别共同的 认知和/或运动障碍的单发、并发或顺序发展的模式 痴呆症患者和非痴呆症患者。这三项研究的信息财富(都是建立的和 在NIA资金的支持下)将进一步扩展并提供给合作研究人员团队 持续的分析。

Abstract/Summary The proposed work will investigate the pathogeneses of late life cognitive and motor impairments attributed to Alzheimer's disease, closely allied cerebrovascular and neurodegenerative diseases, brain aging, and their common patterns of co-occurrence in three existing cohorts: the Honolulu-Asia Aging Study, the Nun Study, and the 90+ Study. Our focus will be on relationships among objective, longitudinal measures of motor function and cognition–with the last obtained proximate to death–and a defined set of neuropathologic substrates identified at autopsy. Parallel and merged analyses will be carried out using existing resources provided from these three large population-based longitudinal studies composed of participants with distinctly different gender, age, and ethnicity. We will leverage these substantial existing resources to test the hypothesis that cognitive and motor impairments that occur with advancing age are syndromic and derive from a partially overlapping mix of diseases that vary among individuals in part by age, sex, and ethnicity, and that can be identified best at the current time by their neuropathologic features. This will allow the identification of common patterns for the singular, concurrent, or sequential development of cognitive and/or motor impairments in persons with and without dementia. The informational wealth of these three studies (all established and supported with NIA funding) will be further expanded and available to teams of collaborating researchers for continuing analyses.