Epidemiology of Aging and Dementia - Autopsy Research

衰老和痴呆症的流行病学 - 尸检研究

• 批准号: 7472351
• 负责人: LON Ray WHITE
• 金额: $ 98.4万
• 依托单位: KUAKINI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-06-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7472351
• 关键词: Accounting; Aging; Alzheimer' s Disease; Amyloid; Amyloid deposition; Ankle; Architecture; Area; Arteries; Asia; Atrophic; Autopsy; Basal Ganglia; Bilateral; Blood; Blood Pressure; Blood Vessels; Brain; Cell Count; Cerebral Amyloid Angiopathy; Cerebral cortex; Cerebral hemisphere; Cerebrovascular Disorders; Characteristics; Chronic; Circle of Willis; Classification; Clinical; Cognition; Collaborations; Data; Dementia; Diabetes Mellitus; Diabetic Angiopathies; Diagnosis; Disease; Education; Elderly; End Point; Epidemiology; Epitopes; Evaluation; Fatty acid glycerol esters; Fibrinogen; Formalin; Framingham Heart Study; Frequencies; Frontotemporal Dementia; Funding; Future; Genes; Genetic Polymorphism; Gliosis; Goals; Grant; Heart; Herpes zoster disease; Hippocampus (Brain); Histologic; Human T-lymphotropic virus 1; Hypertension; Impaired cognition; Impairment; Individual; Infarction; Infection; Investigation; Japanese American; Left; Left cerebral hemisphere; Lesion; Lewy Bodies; Life; Link; Living Wills; Lobe; Location; Measurement; Meninges; Methods; Microglia; Microscopic; Minerals; Myelin; Nested Case-Control Study; Neurites; Neurofibrillary Tangles; Numbers; Parkinson Disease; Participant; Pathologic; Pathologic Processes; Pattern; Perfusion; Phase; Physical Examination; Physical Function; Physical activity; Plasma; Population; Prevention; Prevention program; Prevention strategy; Principal Investigator; Procedures; Process; Proteins; Protocols documentation; Public Health; Purpose; Recording of previous events; Research; Research Personnel; Resources; Risk Factors; Sampling; Sclerosis; Senile Plaques; Series; Serological; Silver stain method; Slide; Smoking; Socioeconomic Status; Staging; Staining method; Stains; Stroke; Study Section; Tauopathies; Testing; Thick; Time; Tissues; Upper arm; Vascular Dementia; Vitamins; Waist-Hip Ratio; Walking; Work; aging brain; astrogliosis; base; brain tissue; cardiovascular risk factor; cerebral atrophy; cognitive function; cohort; density; fitness; improved; men; middle age; neuron loss; programs; research and development; tau Proteins; white matter

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.

描述（由研究者提供）：这笔赠款将支持继续和扩大对日裔美国人的脑老化，痴呆，认知能力下降，帕金森病和中风的尸检研究，由于他们长期参与檀香山心脏计划和檀香山-亚洲老龄化研究，可以获得大量前瞻性收集的信息。其主要目标是提高对这些疾病和晚年损害的病理过程的理解，并确定与代表基本致病过程的脑病变相关的风险因素。截至2005年3月，共进行了615次脑解剖。这一数字将在未来5年内增加约50%。迄今为止的分析表明，缺血性脑血管病是该队列中最常见的与痴呆相关的致病过程（25%的病例），多发性微梗死是最特异和一致的指标。神经纤维缠结（NFT）和/或神经炎性斑块（NP）是20%的痴呆死亡者中与痴呆相关的主要或唯一病变。皮质路易体占痴呆病例的10%，海马硬化占4%，混合（共显性）病变占18%。在其余痴呆死亡者（23%）中发现的异常仅限于全身性萎缩、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策略可能会产生适度的公共卫生影响。我们的研究结果表明，高效的预防方案可能需要同时针对两个或更多的潜在过程。采用神经病理学病变作为终点进行分析，以确定特定潜在致病过程的特定风险因素，作为预防的基本初步步骤。除了增加尸检外，拟议的继续将支持以下方面的努力：（1）微血管缺血性疾病的研究，（2）微梗塞和阿尔茨海默病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，和（4）识别负责脑萎缩和神经胶质增生的主要潜在致病过程，并识别相应的危险因素。