Genetic modifiers of the Mediterranean-DASH diet Intervention for Neurodegenerative Delay (MIND) response

摘要 与年龄相关的认知能力下降的程度因个体而异，这种差异很可能是由 遗传和环境因素的复杂相互作用。地中海式饮食干预 神经退行性延迟(精神)是基于饮食-痴呆症领域最令人信服的证据。 流行病学数据表明，更多地坚持精神饮食可以减缓认知能力下降的速度，并 降低患阿尔茨海默病(AD)的风险。阿尔茨海默病的全基因组关联研究丰富了 映射到与免疫反应和胆固醇代谢有关的基因的变体，可能导致 对饮食等预防措施的反应不同。头脑中强调的食物和营养物质也 已被证明对大脑有有益的影响，可能通过免疫或胆固醇途径调节。 导致人与人之间关键精神成分代谢差异的遗传因素也可能 增强或限制它们的疗效，并最终影响对这种饮食的反应。 心理与认知健康的联系总体上是适度的，但当与个体基因结合时 有关阿尔茨海默病易感性和精神成分代谢的信息，可能揭示阿尔茨海默病的亚群 特别受益于坚持这种饮食的人群。我们的提案充分利用了第一个、持续的思维 试验以及现有的基于社区和人口的数据，以检查(A)AD的遗传差异 易感性和(B)营养新陈代谢改变了对心理饮食的反应。我们的研究将提供 对大脑在减缓认知衰退中可能扮演的角色的机械式洞察，也将使 执行思维，以实现最佳效果。

ABSTRACT Age-associated cognitive decline varies in extent among individuals, and this variation likely arises from a complex interplay of genetic and environmental factors. The Mediterranean-DASH Diet Intervention for Neurodegenerative Delay (MIND) is based on the most compelling evidence in the diet-dementia field. Epidemiological data suggest that greater adherence to the MIND diet slows the rate of cognitive decline and reduces the risk of Alzheimer's disease (AD). Genome-wide association studies of AD are enriched with variants mapping to genes implicated in immune response and cholesterol metabolism, which may result in different responses to preventive measures such as diet. Foods and nutrients emphasized by MIND have also been shown to have beneficial effects on the brain, potentially mediated by immunity or cholesterol pathways. Genetic factors contributing to between-person variation in metabolism of key MIND components may also enhance or limit their efficacy and ultimately impact response to this diet. MIND associations with cognitive health are modest overall but, when combined with individual genetic information concerning AD susceptibility and MIND-component metabolism, may reveal subgroups of the population who especially benefit when adhering to this diet. Our proposal leverages the first, ongoing MIND trial as well as existing community- and population-based data to examine how genetic differences in (a) AD predisposition and (b) nutrient metabolism modify the response to the MIND diet. Our research will provide mechanistic insights into the role that MIND may play in slowing cognitive decline and will also inform the implementation of MIND for optimal effectiveness.