Influence of Dietary Fish and mercury Exposure on Brain health and Dementia

描述（由申请人提供）：该应用程序建议使用现有的前瞻性纵向临床神经病理学研究，记忆和衰老项目（MAP）的数据来检查大脑中汞（Hg）和硒（Se）的水平是否与脑神经病理学（A¿，神经原纤维结，脑梗死，路易体），炎症（小胶质细胞）和神经储备（突触蛋白密度），临床结果（认知功能，运动功能，轻度认知障碍，阿尔茨海默病）相关。以及死前几年的鱼消费量。这个小组和其他人最近的研究表明，食用鱼类和海洋n-3脂肪酸可以保护大脑免受痴呆和认知能力下降的影响。鱼类也是环境毒素甲基汞（MeHg）和氧化神经保护营养素硒的来源。对神经认知发育的研究表明，鱼类摄入的n-3脂肪酸、DHA和硒的有益作用被高浓度的甲基汞所抵消。关于是否对衰老的人类大脑也有有害影响的研究有限。本申请申请资金，通过分析200名已故MAP参与者死后脑组织中的汞和硒来进一步研究这些关系，这些参与者都有多年来每年收集的饮食和临床结果数据。这项研究将调查死后大脑中汞和硒的含量是否与死前几年的鱼类摄入量有关。该研究将验证以下假设：1)较高的脑汞水平将与更严重的神经病理和炎症、更少的神经储备、MCI、AD、认知和运动能力下降的高风险相关；2)较高的硒水平与更大的神经储备、更少的神经病理和炎症、更低的MCI、AD和认知和运动能力下降的风险相关；3)汞和硒对脑部病理和临床神经预后具有协同作用，4)鱼类消费有助于这些关联。人们被鼓励吃鱼来预防心脏病、中风和痴呆。这项研究的结果将告知公众，在这些建议中是否应考虑鱼类的汞含量。

DESCRIPTION (provided by applicant): The application proposes to use data from an existing prospective, longitudinal clinical-neuropathological study, the Memory and Aging Project (MAP) to examine whether brain levels of mercury (Hg) and selenium (Se) are related to brain neuropathology (A¿, neurofibrillary tangles, cerebral infarcts, Lewy bodies), inflammation (microglia), and neural reserve (synaptic protein density), to clinical outcomes (cognitive function, motor function, mild cognitive impairment, Alzheimer disease), and to fish consumption measured in the years before death. Recent studies by this group and others suggest that consumption of fish and marine n-3 fatty acids may protect the brain against dementia and cognitive decline. Fish are also a source of the environmental toxin, methyl mercury (MeHg), and the oxidative neuroprotectant nutrient, Se. Studies of neurocognitive development have demonstrated that the beneficial effects of the n-3 fatty acid, DHA and Se consumed in fish are offset by high levels of MeHg. There is limited study on whether there are also deleterious effects on the aging human brain. This application requests funds to examine these relations further by analyzing Hg and Se in post-mortem brain tissue among 200 deceased MAP participants, all of whom have years of annually collected data on diet and clinical outcomes. The study will examine whether post-mortem brain levels of Hg and Se are associated with fish consumption in the years before death. The study will test the hypotheses: 1) that higher brain levels of Hg will be associated with greater neuropathology and inflammation, less neural reserve, and higher risk of MCI, AD, and cognitive and motor decline; 2) higher levels of Se will be associated with greater neural reserve, less neuropathology and inflammation, lower risk of MCI, AD, and cognitive and motor decline; 3) that Hg and Se have a synergistic effect on brain pathologies and clinical neurological outcomes, and 4) that fish consumption contributes to these associations. The population is encouraged to consume fish to protect against heart disease, stroke, and dementia. Results of this study will inform the public on whether Hg content of fish should be considered in these recommendations. PUBLIC HEALTH RELEVANCE: The growing older population is encouraged to consume fish to benefit health; however, the aging brain may be particularly vulnerable to the toxic effects of MeHg contained in fish. The current application will investigate the independent and co- dependent effects of brain levels of Se and Hg on brain health and neurological disease as well as to dietary consumption of fish. Whatever the study results, this will be important information to the public health.