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

描述(由申请人提供)：申请者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的汞(Hg)和硒(Se)水平是否与脑神经病理(A？、神经原纤维缠结、脑梗塞、路易体)、炎症(小胶质细胞)和神经储备(突触蛋白密度)、与临床结果(认知功能、运动功能、轻度认知障碍、阿尔茨海默病)以及以死亡前几年测量的鱼类摄入量有关。该小组和其他人最近的研究表明，食用鱼类和海洋n-3脂肪酸可能会保护大脑免受痴呆症和认知能力下降的影响。鱼也是环境毒素甲基汞(MeHg)和氧化性神经保护剂营养物Se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Se的有益影响被高水平的甲基汞所抵消。关于它是否对老化的人脑也有有害影响的研究有限。这项申请要求资金，通过分析200名已故MAP参与者的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的饮食和临床结果的年度收集数据。这项研究将研究死后大脑中汞和硒的水平是否与死前几年的鱼类消费有关。这项研究将检验假设：1)大脑中汞水平较高将与更多的神经病理和炎症、较少的神经储备以及MCI、AD以及认知和运动功能下降的风险相关；2)更高的Se水平将与更多的神经储备、较少的神经病理和炎症、较低的MCI、AD以及认知和运动功能下降的风险相关；3)汞和Se对大脑病理和临床神经学结果具有协同作用；以及4)鱼的摄入有助于这些关联。鼓励人们食用鱼类以预防心脏病、中风和痴呆症。这项研究的结果将告知公众，这些建议是否应考虑鱼类的汞含量。 与公共健康相关：鼓励不断增长的老年人口食用鱼类以促进健康；然而，老化的大脑可能特别容易受到鱼类中所含甲基汞的毒性影响。目前的应用将调查大脑中硒和汞水平对大脑健康和神经疾病以及鱼类饮食消费的独立和相互依赖的影响。无论研究结果如何，这都将是对公众健康的重要信息。

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.