Genetic Epidemiology of Caffeine and Cognitive Decline

项目总结 与年龄相关的认知衰退是一种重要的人类疾病，其程度因个体而异。 这种变异很可能是遗传和环境因素的复杂相互作用造成的。咖啡因是最多的 世界上普遍摄入的行为活性物质，越来越多的文献指出 前提是咖啡因可以提供安全、有效、容易获得和廉价的治疗剂 对抗认知功能减退。然而，导致咖啡因新陈代谢变化的因素可能与 咖啡因的摄入量和修改其与认知能力下降的关系。此外，咖啡因针对的是基因和 潜在地影响认知衰退的途径，从而提供了一个机会来促进我们对 如果不考虑咖啡因代谢的变化，这种情况可能会被忽略。 Cornelis博士提出了一项培训和研究计划，这将有助于她成为一名独立的 营养和认知衰退的系统流行病学研究员。获得i)认知方面的培训 功能评估II)认知衰退的流行病学和III)认知衰退的神经病理方面 和阿尔茨海默氏症，她将与来自两个国家的国际公认的导师团队密切合作 声誉良好的机构致力于老龄研究并从事包括课程工作在内的培训活动， 一对一和小组会议、研讨会和会议、观察和实践 包括对咖啡因和大脑DNA甲基化的初步研究。 她将把她的训练应用到第一次全面而高效的遗传学联合效应分析中。 咖啡因对认知功能下降的影响。咖啡因代谢率和咖啡因暴露的综合指数将为 在流行病学荟萃分析框架中用于检查基因咖啡因摄入的相互作用和 认知功能下降，并通过模拟单核苷酸咖啡因暴露交互作用发现该疾病的新基因座 在全基因组范围内。 Cornelis博士的研究将为咖啡因在减缓反应中的潜在作用提供关键的见解 认知能力下降，并有可能发现这种情况下的新的生物学途径。结果： 这项工作应该为认知障碍和发展新的行为能力培养新的研究思路 以及安全有效的治疗和预防的药理途径。此外，这一经历和 完成科内利斯博士的培训和研究计划所获得的知识将使她能够获得 R01基金，以获取更多系统级数据，以了解咖啡因或咖啡因如何 其他饮食因素也会影响认知能力下降。

PROJECT SUMMARY Age-associated cognitive decline is an important human condition that varies in extent among individuals. This variation likely arises from a complex interplay of genetic and environmental factors. Caffeine is the most commonly ingested behaviorally active substance in the world, and a growing body of literature points to the premise that caffeine may provide a safe, effective, readily available, and inexpensive therapeutic agent against cognitive decline. However, factors that contribute to variation in caffeine metabolism may interact with caffeine intake and modify its association with cognitive decline. Furthermore, caffeine targets genes and pathways potentially impacting cognitive decline and thus an opportunity to advancing our understanding of this condition may be missed if variation in caffeine metabolism is left unaccounted for. Dr. Cornelis proposes a training and research plan that will contribute to her goal to become an independent investigator of systems epidemiology of nutrition and cognitive decline. To acquire training in i) cognitive function assessment ii) epidemiology of cognitive decline and iii) neuropathological aspects of cognitive decline and Alzheimer's disease, she will work closely with a team of internationally recognized mentors from two highly reputable institutes committed to aging research and engage in training activities including coursework, one-on-one and small group sessions, seminars and conferences, observation and hands-on practicum including a pilot study of caffeine and brain DNA methylation. She will apply her training to the first comprehensive and highly efficient analysis of the joint effects of genetics and caffeine on cognitive decline. Composite indices of caffeine metabolic rate and caffeine exposure will be used in an epidemiological meta-analytical framework to examine genecaffeine intake interactions and cognitive decline and to discover novel loci for this condition by modeling SNPcaffeine exposure interactions on a genome-wide scale. Dr. Cornelis's research will provide critical insights into the role that caffeine potentially plays in slowing cognitive decline and has potential to uncover novel biological pathways underlying this condition. Results of this work should foster new lines of investigation for cognitive impairment and for developing novel behavioral and pharmacological avenues for safe and effective treatment and prevention. Moreover, the experience and knowledge obtained from the completion of Dr. Cornelis's training and research plan will allow her to obtain R01 funding to acquire additional systems-level data for a more detailed mechanistic view of how caffeine or other dietary factors impact cognitive decline.