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

摘要/概要 拟议的工作将调查归因于老年认知和运动障碍的发病机制， 阿尔茨海默氏病，密切相关的脑血管和神经退行性疾病，脑老化，及其 在三个现有的队列中共同发生的常见模式：檀香山-亚洲老龄化研究，修女研究， 90+研究我们的重点将是运动功能的客观，纵向措施之间的关系 和认知--最后一次是在临近死亡时获得的--以及一组确定的神经病理学基质 尸体解剖时发现的将利用下列机构提供的现有资源进行平行和合并分析： 这三项大型的基于人群的纵向研究由具有明显不同 性别年龄和种族我们将利用这些大量的现有资源来检验假设， 随着年龄的增长而发生的认知和运动障碍是综合征， 疾病的重叠混合，部分因年龄、性别和种族而异， 目前通过其神经病理学特征最好地确定。这将有助于识别常见的 认知和/或运动障碍的单一、并发或顺序发展模式 患有和不患有痴呆症的人。这三项研究的信息财富（均已建立， 在NIA资金的支持下）将进一步扩大，并提供给合作研究人员团队， 继续分析。

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.