Epidemiology of Brain Aging in the Very Old

申请者描述(申请人提供)：本申请是“老年脑老化流行病学”项目的延续，该项目是一项以人群为基础的关于阿尔茨海默病(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。该队列由日裔美国男性组成，他们自1965年以来一直在火奴鲁鲁心脏计划(HHP)和自1991年以来在火奴鲁鲁-亚洲老龄化研究(HAAS)中接受跟踪。应计资源包括多个以前检查周期的标准化计量和观察结果。自1991年以来，这些评估包括对认知和运动功能的评估。几乎所有参与者都可以获得冷冻的血液样本和DNA。多导睡眠图研究和核磁共振扫描可以对子样本进行，广泛的神经病理数据是从正在进行的、单独资助的脑病理项目中收集的。在2001-06年度资助期内完成了两个审查周期。识别AD、VAD、DLB和PD的事件案例，以及广泛的风险因素分析，导致了几份已发表的报告。经神经病理证实的混合性痴呆发生率较高。出乎意料的是，在年龄最大的受试者中，帕金森病的发病率下降了，而痴呆症的发病率却稳步上升。继续的中心目标将是：1)估计87岁至105岁之间痴呆症、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风险因素和决定因素，特别是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(由其他赠款支持)。初步检查开始时，目标样本将包括大约1100名幸存的参与者。我们预计将检查767(75%)。将每隔一年进行三次检查，并每6个月与家庭报案人进行一次标准化的电话面谈。初试时最年轻的参与者将为87岁。在最后一个延续周期中，年龄最大的预计为112岁。这些更频繁的接触有望加强与家人的融洽关系，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。国家阿尔茨海默病患者协调中心的统一数据集将用于诊断标准和方法，一名专家神经心理学家将加入核心调查团队。HAAS的独特设计和资源将使我们对这些疾病的发病机制的了解有所改善，进而制定预防或延缓老年疾病进展的策略。

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.