Epidemiologic Study of Brain Vitamin E, Diet & Age-Related Neurologic Diseases

这是申请（1 R 01 NS 056397）的第二次修订，“脑维生素E、饮食和脑相关神经系统疾病的流行病学研究”， 没有资金支持。本申请提出使用来自现有纵向临床病理研究，宗教秩序研究， 分析450名死者死后脑组织和脑脊液中各种形式维生素E的生化水平 以及神经病理学和神经储备、氧化、炎症和胰岛素活性的选定标志物，并前瞻性地收集 整个800名参与者队列的年度膳食暴露数据。宗教秩序研究将免费提供给拟议的研究， 关于所有非饮食风险因素的数据，关于神经系统疾病以及认知和运动功能的所有临床结局数据，以及关于 脑组织的死后神经病理学这个小组和其他人最近的研究表明，目前在人体内的高剂量α-生育酚， 在临床试验中测试，可能不是有效的治疗剂。如果得到资助，这项研究将具有前所未有的能力， 将大脑中各种形式的维生素E水平与阿尔茨海默病（AD）和帕金森病相关的临床病理结果联系起来， 迹象以及饮食暴露。拟议中的多学科小组进行了一项试点研究，表明大脑中的伽马和 α-生育酚与AD神经病理学和帕金森症状的严重程度呈负相关，与语义记忆呈正相关。 在整个队列中证实这些关联对公共卫生至关重要，特别是考虑到 这些疾病的衰弱和不可治愈的性质，以及它们在美国人口中增长最快的年龄组中的高发生率。 主要研究者/项目负责人（最后，第一，中间）：Morris，Martha克莱尔这是第二次修订R 01申请，以研究 在现有的纵向临床研究中， - 病理学研究，宗教秩序研究。

This is the second revision of an application (1 R01 NS056397), "Epidemiologic Study of Brain Vitamin E, Diet and Age-Related Neurologic Diseases", which was not funded. This application proposes to use data from an existing longitudinal clinical-pathologic study, the Religious Orders study, to analyze biochemical levels of the various forms of vitamin E in post-mortem brain tissue and cerebrospinal fluid in 450 deceased participants as well as selected markers of neuropathology and neural reserve, oxidation, inflammation, and insulin activity, and to collect prospectively annual dietary exposure data on the entire cohort of 800 participants. The Religious Orders Study will provide at no cost to the proposed study, data on all non-dietary risk factors, all clinical outcome data on neurological diseases and cognitive and motor function, and most data on post-mortem neuropathology of brain tissue. Recent studies by this group and others suggest that high-dose a-tocopherol, which is currently being tested in clinical trials, may not be the effective therapeutic agent. If funded, the proposed study will have the unprecedented ability to relate brain levels of the various forms of vitamin E to clinical- pathologic outcomes relevant to Alzheimer's disease (AD) and parkinsonian signs as well as to dietary exposures. The proposed multidisciplinary team conducted a pilot study that suggests brain levels of both gamma and alpha tocopherols are inversely related with AD neuropathology and severity of parkinsonian signs, and positively associated with semantic memory. Substantiation of these associations in the entire cohort would be of the utmost importance to the public health, especially given the debilitating and incurable nature of these diseases, and their high occurrence among the fastest growing age group in the US population. Principal Investigator/Program Director (Last, First, Middle): Morris, Martha Clare This is the second revised R01 application to investigate the relations of tocopherols in the brain to age-related neurological diseases and to dietary tocopherols in an existing longitudinal clinical -pathologic study, the Religious Orders Study.