Epidemiology of Aging and Damentia - Autopsy Research

衰老和痴呆的流行病学 - 尸检研究

• 批准号: 7812728
• 负责人: LON Ray WHITE
• 金额: $ 96.05万
• 依托单位: KUAKINI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-15 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7812728
• 关键词: Address; Age-associated memory impairment; Aged, 80 and over; Aging; Ally; Alzheimer' s Disease; Architecture; Area; Arts; Atrophic; Autopsy; Biological Preservation; Blood; Blood Vessels; Brain; Brain region; Categories; Cerebellum; Chronic; Classification; Cognitive; Collaborations; Complex; Consultations; Data; Dementia; Detection; Deterioration; Development; Diagnosis; Digital Photography; Economics; Elderly; Employee; Epidemiology; Equipment; Formalin; Frequencies; Frontotemporal Lobar Degenerations; Funding; Gliosis; Grant; Gray unit of radiation dose; Hand; Heterogeneity; Hippocampus (Brain); Histologic; Histopathology; Human; Impaired cognition; Individual; Infarction; Inflammatory; Investigation; Ischemia; Joints; Laboratories; Lesion; Leukoencephalopathy; Link; Living Wills; Luxol Fast Blue MBS; Magnetic Resonance Imaging; Methods; Microscope; Microscopic; Motor Neuron Disease; Neocortex; Paraffin; Paraffin Embedding; Parents; Participant; Pathogenesis; Pathologic; Pathologic Processes; Pattern; Persons; Phase; Physical Examination; Population; Prevention strategy; Principal Investigator; Process; Protocols documentation; Public Health; Publications; Reading; Recovery; Research; Research Personnel; Resolution; Risk Factors; Role; Sampling; Sclerosis; Shapes; Site; Slide; Staging; Staining method; Stains; Structure; Temporal Lobe; Testing; Thick; Time; Tissue Sample; Tissues; Training; U-Series Cooperative Agreements; Ubiquitin; United States National Institutes of Health; Vascular Dementia; Work; aged; base; brain tissue; comparison group; design; expectation; gray matter; insight; neocortical; neuron loss; parent grant; programs; public health relevance; response; white matter

DESCRIPTION (provided by principal investigator): Our application is in response to NOT-OD-09-058: NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications. The parent grant is 5U01AG017155-08, Epidemiology of Aging and Dementia-Autopsy Research. We will address three distinct neuropathologic abnormalities found in the brains of substantial proportions of demented HAAS decedents, but that were not recognized as important causes of cognitive deterioration when the parent grant was originally designed. They are: 1) dementia lacking distinctive histopathology, 2) hippocampal sclerosis, and 3) microinfarcts. All relevant brain materials are available "wet" (in neutral formalin) or paraffin embedded. Subset panels for each of these three lesion types have been selected to minimize ambiguity related to co-morbid lesions, and for the examination of relevant comparison groups. Intensive state-of-the-art histologic methods will be applied to these panels to define their possible relationships with other known conditions (fronto-temporal dementia, motor neuron disease, chronic ischemia or chronic inflammatory states) as well as to examine possible inter-relatedness and occurrence in non-impaired decedents. Research on microinfarcts will greatly extend our understanding of optimal methods for their detection, of their distribution throughout the brain in relation to cognitive impairment, and will provide a basis for pathologic criteria for the diagnosis of "multi-microinfarct dementia" as a major category of vascular cognitive impairment. Research bearing on MRI approaches to the diagnosis of multi-microinfarct dementia during life will be carried out using brain tissues selected to be maximally informative for these purposes. The results of these efforts will have a major impact on current concepts related to the causes of dementia in late life, and will be highly relevant to the development of preventive strategies to reduce the human and public health burden of these terrible afflictions. Major economic benefits are related to the support of new employees, increasing the level of effort of part time employees, and the purchase of essential laboratory equipment and materials needed to carry out the proposed work. PUBLIC HEALTH RELEVANCE: The results of our research will have a major impact on current concepts related to the causes of dementia in late life, and will be highly relevant to the development of preventive strategies to reduce the human and public health burden of these terrible afflictions.

描述（由首席研究员提供）：我们的申请是为了回应 NOT-OD-09-058：NIH 宣布恢复法案基金可用于竞争性修订申请。家长拨款是 5U01AG017155-08，衰老和痴呆流行病学尸检研究。我们将解决在大部分痴呆 HAAS 死者大脑中发现的三种不同的神经病理学异常，但在最初设计家长补助金时，这些异常并没有被认为是认知恶化的重要原因。它们是：1) 缺乏独特组织病理学的痴呆，2) 海马硬化，3) 微梗死。所有相关的脑材料均可“湿”（在中性福尔马林中）或石蜡包埋。针对这三种病变类型中的每一种都选择了子集组，以尽量减少与共病病变相关的歧义，并用于检查相关比较组。最先进的强化组织学方法将应用于这些小组，以确定它们与其他已知疾病（额颞叶痴呆、运动神经元疾病、慢性缺血或慢性炎症状态）的可能关系，并检查未受损死者中可能的相互关联性和发生情况。对微梗塞的研究将极大地扩展我们对微梗塞最佳检测方法的理解，以及它们在整个大脑中与认知障碍相关的分布，并将为诊断“多发微梗塞性痴呆”作为血管性认知障碍的主要类别的病理标准提供基础。将使用为这些目的而选择的能提供最大信息的脑组织来进行与 MRI 方法相关的研究，以诊断一生中的多发微梗塞性痴呆。这些努力的结果将对当前与晚年痴呆症病因相关的概念产生重大影响，并将与制定预防策略高度相关，以减轻这些可怕疾病给人类和公共卫生带来的负担。主要的经济效益与新员工的支持、兼职员工的努力水平的提高以及执行拟议工作所需的必要实验室设备和材料的购买有关。 公共卫生相关性：我们的研究结果将对当前与晚年痴呆症病因相关的概念产生重大影响，并将与制定预防策略高度相关，以减轻这些可怕疾病给人类和公共卫生带来的负担。