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

摘要 脑卒中相关的认知能力下降在个体之间的程度不同，这种变化可能源于 遗传和环境因素的复杂相互作用。Mediterranean DASH饮食干预 神经退行性延迟（MIND）是基于饮食痴呆领域最令人信服的证据。 流行病学数据表明，更多地坚持MIND饮食可以减缓认知能力下降的速度， 降低阿尔茨海默病（AD）的风险。AD的全基因组关联研究丰富了 与免疫反应和胆固醇代谢有关的基因的变异，这可能导致 对饮食等预防措施的不同反应。MIND强调的食物和营养素也 已被证明对大脑有益，可能通过免疫或胆固醇途径介导。 遗传因素导致人与人之间的代谢变化的关键精神成分也可能 增强或限制其功效并最终影响对这种饮食的反应。 总体而言，MIND与认知健康的关联是适度的，但当与个体遗传因素相结合时， 关于AD易感性和MIND成分代谢的信息，可能揭示了 特别是那些坚持这种饮食的人。我们的提案利用了第一个正在进行的MIND 试验以及现有的社区和人口为基础的数据，以研究如何在遗传差异（a）AD 易感性和（B）营养代谢改变对MIND饮食的反应。我们的研究将提供 对MIND在减缓认知能力下降方面可能发挥的作用的机械性见解，也将告知 实施MIND以获得最佳效果。

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.