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

描述（由申请人提供）：该申请建议使用现有前瞻性纵向临床神经病理学研究（记忆与衰老项目（MAP））的数据，以检查大脑中汞（Hg）和硒（Se）的水平是否与大脑神经病理学相关（A？、神经纤维缠结、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），以及死亡前几年测量的鱼类消费量。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）和氧化性神经保护营养素Se的来源。对神经认知发育的研究表明，从鱼类中摄取的n-3脂肪酸、DHA和硒的有益效果会被高含量的甲基汞抵消。关于是否对老化的人类大脑也有有害影响的研究有限。该申请要求提供资金，通过分析200名死亡MAP参与者的死后脑组织中的汞和硒，进一步研究这些关系，所有这些参与者都有多年的饮食和临床结果的年度收集数据。这项研究将检查死后大脑中汞和硒的水平是否与死亡前几年的鱼类消费有关。本研究将检验以下假设：1）脑内汞含量越高，神经病理和炎症越严重，神经储备越少，MCI、AD、认知和运动能力下降的风险越高; 2）硒含量越高，神经储备越大，神经病理和炎症越少，MCI、AD、认知和运动能力下降的风险越低; 3）汞和硒对大脑病理和临床神经学结果具有协同效应，以及4）鱼类消费有助于这些关联。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，在这些建议中是否应考虑鱼类的汞含量。 公共卫生相关性：鼓励越来越多的老年人食用鱼类以促进健康;然而，老年人的大脑可能特别容易受到鱼类中所含甲基汞的毒性影响。目前的应用将调查脑硒和汞水平对脑健康和神经系统疾病的独立和共同依赖的影响，以及饮食中的鱼类消费。无论研究结果如何，这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.