Epidemiology of Aging and Dementia-Autopsy Research

这笔赠款将支持继续和扩大关于脑老化、痴呆症、 认知能力下降、帕金森氏症和中风的日裔美国男性对他们来说 通过他们对火奴鲁鲁的长期参与，可以获得预期收集的信息 心脏计划和檀香山-亚洲老龄化研究。主要目标是提高对 在晚年这些疾病和损伤的基础上的病理过程，并确定危险因素 与代表基本致病过程的脑损伤有关。截至2005年3月a 总共进行了615例脑部尸检。这一数字将比 未来5年的进程。迄今的分析表明，缺血性脑血管疾病是 在这个队列中，致病过程最常与痴呆症有关(25%的病例)，并发现多个 微梗塞作为最特异、最一致的指标。神经原纤维缠绕(NFT)和/或神经炎 在20%的痴呆患者中，斑块(NP)是与痴呆相关的主要或唯一病变 继承人。皮质路易体占10%，海马区硬化症占4%，混合型(co. 18%的痴呆症患者有明显的病损。在剩下的痴呆患者中发现了异常 死者(23%)仅限于广泛性萎缩、神经胶质增生症和神经元丢失--并不涉及特定的 致病机制。在这一人群中，减少NFT和NP负担的预防策略 在不影响其他进程的情况下，可能会对公共卫生产生适度的影响。我们的发现 建议高效的预防计划可能需要同时针对两个或两个或 更多的潜在过程。使用神经病理损伤作为终点的分析是 为确定特定潜在致病过程的特定风险因素而进行的 向预防迈出必要的初步步骤。除了积累更多的尸检外，拟议的 继续努力将支持(1)微血管缺血性疾病研究，(2) 微梗塞的分布和密度与阿尔茨海默病皮损的关系 Willis动脉环结构特征与脑内病变的关系 脑实质，以及(4)确定脑的主要潜在致病过程 萎缩和胶质化，并确定相应的危险因素。

This grant will support continuation and expansion of autopsy research on brain aging, dementia, cognitive decline, Parkinson's disease, and stroke in Japanese American men for whom a wealth of prospectively collected information is available by virtue of their long-standing participation in the Honolulu Heart Program and Honolulu-Asia Aging Study. The principal goal is to improve understanding of the pathologic processes that underlie these illnesses and impairments in late life, and to identify risk factors associated with the brain lesions that represent the essential pathogenic processes. As of March 2005 a total of 615 brain autopsies had been done. This number will increase by approximately 50% over the course of the upcoming 5 years. Analyses to date implicate ischemic cerebrovascular disease as the pathogenic process most frequently linked to dementia in this cohort (25% of cases) and identify multiple microinfarcts as the most specific and consistent indicator. Neurofibrillary tangles (NFT) and/or neuritic plaques (NP) are the dominant or sole lesions associated with dementia in 20% of the demented decedents. Cortical Lewy bodies account for 10%, hippocampal sclerosis for 4%, and mixed (co- dominant) lesions for 18% of the dementia cases. Abnormalities identified in the remaining demented decedents (23%) were limited to generalized atrophy, gliosis, and neuron loss - not implicating a specific pathogenic mechanism. In this population, prevention strategies that reduce the burden of NFT and NP without influencing the other processes would likely have a modest public health impact. Our findings suggest that highly effective prevention programs are likely to require simultaneous targeting of two or more of the underlying processes. Analyses employing neuropathologic lesions as endpoints are conducted in an effort to identify specific risk factors for specific underlying pathogenic processes as an essential preliminary step toward prevention. In addition to accruing additional autopsies, the proposed continuation will support efforts directed toward (1) studies of microvascular ischemic disease, (2) relationships between distributions and densities of microinfarcts and Alzheimer's lesions, (3) relationships between structural characteristics of Circle of Willis arteries and lesions in the brain parenchyma, and (4) identification of the major underlying pathogenic processes responsible for brain atrophy and gliosis, and identification of corresponding risk factors.