Epidemiology of Aging and Dementia - Autopsy Research

描述(由研究人员提供)：这笔赠款将支持继续和扩大对日裔美国男性的大脑老化、痴呆症、认知衰退、帕金森病和中风的尸检研究，由于他们长期参与火奴鲁鲁心脏计划和火奴鲁鲁-亚洲老龄化研究，他们可以获得大量前瞻性收集的信息。主要目标是提高对晚年这些疾病和损伤背后的病理过程的了解，并确定与代表基本致病过程的脑损伤相关的风险因素。截至2005年3月，共进行了615例脑部尸检。在接下来的5年中，这一数字将增加约50%。到目前为止的分析表明，缺血性脑血管疾病是该队列中最常见的与痴呆症有关的致病过程(25%的病例)，并将多发性微梗塞确定为最特异和一致的指标。神经纤维缠结(NFT)和/或神经炎斑块(NP)是与痴呆相关的主要或唯一病变，占痴呆死者的20%。在痴呆症患者中，皮质路易体占10%，海马硬化占4%，混合性(共显性)病变占18%。在剩下的痴呆患者(23%)中发现的异常仅限于广泛性萎缩、胶质增生和神经元丢失--并不涉及特定的致病机制。在这一人群中，减少NFT和NP负担而不影响其他过程的预防战略可能会对公共卫生产生适度的影响。我们的发现表明，高效的预防计划可能需要同时针对两个或两个以上的潜在过程。使用神经病理损伤作为终点进行分析，以努力确定特定潜在致病过程的特定风险因素，作为预防的重要初步步骤。除了积累更多的尸检外，拟议的继续工作还将支持以下方面的工作：(1)微血管缺血性疾病的研究；(2)微梗塞和阿尔茨海默氏症病变的分布和密度之间的关系；(3)威利斯动脉环的结构特征与脑实质病变之间的关系；(4)确定导致脑萎缩和胶质增生的主要潜在致病过程，以及确定相应的风险因素。

DESCRIPTION (provided by investigator): 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 (codominant) 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.