Epidemiology of Aging and Dementia-Autopsy Research

这笔赠款将支持继续和扩大对脑老化，痴呆症， 认知能力下降，帕金森氏病，和中风的日裔美国人，他们的财富， 由于他们长期参与檀香山的活动， 心脏计划和檀香山-亚洲老龄化研究。主要目标是提高对 这些疾病和晚年损伤的病理过程，并确定风险因素 与代表基本致病过程的脑部病变相关。截至2005年3月a 总共进行了615次脑解剖。这一数字将比2010年增加约50%。 未来五年的发展方向。迄今为止的分析表明，缺血性脑血管病是 在该队列中，最常与痴呆相关的致病过程（25%的病例），并确定了多种 微梗死作为最具体和一致的指标。神经纤维缠结（NFT）和/或神经炎 斑块（NP）是20%的痴呆患者中与痴呆相关的主要或唯一病变 死者皮质Lewy小体占10%，海马硬化占4%，混合型（共- 显性）病变的18%的痴呆症病例。在剩下的痴呆症患者中发现了精神分裂症 死亡者（23%）仅限于全身性萎缩、神经胶质增生和神经元丢失--不涉及特定的 致病机理在这一人群中，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。我们的研究结果 这表明，高效的预防方案可能需要同时针对两个或两个以上的目标， 更多的潜在过程。采用神经病理学病变作为终点的分析如下： 进行的努力，以确定特定的潜在致病过程的特定风险因素， 为预防迈出了重要的第一步。除了增加尸检外， 继续将支持致力于（1）微血管缺血性疾病的研究，（2） 微梗死的分布和密度与阿尔茨海默病病变之间的关系，（3） Willis动脉环结构特征与脑内病变的关系 实质，以及（4）识别负责大脑的主要潜在致病过程 萎缩和神经胶质增生，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.