Epidemiology of Brain Aging in the Very Old

描述（由申请人提供）：本申请是“老年人脑老化流行病学”项目的延续，该项目是一项基于人群的阿尔茨海默病（AD）、血管性痴呆（VaD）、路易体痴呆（DLB）、轻度认知障碍（MCI）和帕金森病（PD）的纵向研究。研究对象包括日裔美国男性，他们从1965年开始参加檀香山心脏项目（HHP），从1991年开始参加檀香山-亚洲老龄化研究（HAAS）。累积资源包括标准化测量和多个先前检查周期的观察结果。自1991年以来，这些评估包括认知和运动功能的评估。几乎所有参与者都可以获得冷冻血液样本和DNA。多导睡眠图研究和核磁共振扫描可用于亚样本，并从正在进行的单独资助的脑病理学项目中收集广泛的神经病理学数据。二零零一至零六年度拨款期内完成了两个审查周期。对AD、VaD、DLB和PD病例的鉴定以及广泛的风险因素分析导致了几篇已发表的报告。神经病理学证实混合性痴呆发生率高。出乎意料的是，老年受试者的帕金森病发病率下降，而痴呆症发病率稳步上升。续订的中心目标将是：1)估计87岁至105岁之间痴呆、AD、VaD、DLB、PD和MCI的发病率和临床下降轨迹；2)确定这些疾病的其他危险因素和决定因素，特别关注心血管因素与神经退行性疾病的关系；3)死亡并接受尸检的参与者的临床特征和终点与神经病理学结果的相关性（由其他资助支持）。当初始检查开始时，目标样本将由大约1,100名幸存的参与者组成。我们预计检查767例（75%）。每隔1.5年进行三个检查周期，每隔6个月对举报人家庭进行标准化电话采访。初试时最年轻的参与者为87岁。在最后的延续周期中，年龄最大的预计为112岁。这些更频繁的接触有望加强与家庭成员的关系，改善我们对生命最后几个月功能衰退的评估，并提高尸检率。国家阿尔茨海默病协调中心统一数据集将用于诊断标准和方法，一位神经心理学专家将加入核心研究小组。HAAS的独特设计和资源将提高我们对这些疾病机制的理解，反过来，预防或延缓它们在老年人中的进展的策略。

DESCRIPTION (provided by applicant): This application is for the continuation of the project, "Epidemiology of Brain Aging in the Very Old", a population-based longitudinal study of Alzheimer's disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB), mild cognitive impairment (MCI), and Parkinson's disease (PD). The cohort consists of Japanese-American men who have been followed in the Honolulu Heart Program (HHP) since 1965 and in the Honolulu-Asia Aging Study (HAAS) since 1991. Accrued resources include standardized measurements and observations from multiple prior examination cycles. Since 1991 these have included assessments of cognitive and motor function. Frozen blood samples and DNA are available for nearly all participants. Polysomnography studies and MRI scans are available on sub-samples, and extensive neuropathologic data are collected from ongoing, separately funded brain pathology projects. Two examination cycles were completed during the 2001-06 funding period. Identification of incident cases of AD, VaD, DLB, and PD, and extensive risk factor analyses resulted in several published reports. Neuropathologically confirmed mixed dementia was found to occur with high frequency. Unexpectedly, incidence of PD declined in the oldest subjects while dementia showed a steady rise. The central aims of the continuation will be: 1) estimation of incidence and clinical trajectories of decline for dementia, AD, VaD, DLB, PD, and MCI, between ages 87 and 105 years, 2) identification of additional risk factors and determinants for these conditions, with a special focus or relationships of cardiovascular factors to neurodegenerative conditions, and 3) correlation of clinical features and endpoints with neuropathological findings for participants who die and receive post-mortem examinations (supported by other grants). The target sample will be comprised of approximately 1,100 surviving participants when the initial examination begins. We expect to examine 767 (75%). Three examination cycles will be conducted at 1.5 year intervals, plus standardized telephone interviews with family informants at 6 month intervals. The youngest participant will be 87 years at the initial examination. The oldest at the final continuation cycle is expected be 112 years. These more frequent contacts are expected to enhance rapport with family members, improve our assessments of functional decline in the final months of life, and increase autopsy rates. The National Alzheimers Coordinating Center Uniform Data Set will be used for diagnostic criteria and methods and an expert neuropsychologist will join the team of core investigators. The unique design and resources of the HAAS will lead to improvements in our understanding of disease mechanisms for these conditions, and in turn, to strategies to prevent or delay their progression in the very old.