Gene-diet interaction effects on brain function in middle age




Oleson, Stephanie Marie

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Cognitive decline in older age is a significant public health concern in the face of a globally expanding population and lack of effective therapies for dementia. Thus, identifying modifiable risk factors that affect brain integrity is imperative for preserving cognitive function throughout the lifespan. Accumulating evidence suggests dietary factors plan an important role in cognitive health. Epidemiological data suggests that high sugar and saturated fat (SFA) intake is associated with poorer cognitive outcomes, while research points toward a protective role of polyunsaturated fat (PUFA) intake against dementia. In particular, greater omega-3 (ω-3) PUFA consumption is seen as especially beneficial for brain health. However, effect sizes in intervention-based supplementation studies have been small, highlighting the need for further research to elucidate the underlying mechanisms and contributing factors to dietary effects on the brain. Therefore, the major aim of Study 1 was to conduct a novel investigation of the association between major macronutrient intake (PUFA, SFA, carbohydrates, and protein) and cerebral metabolism in middle-aged adults. The study utilized proton magnetic resonance spectroscopy to quantify cerebral metabolites of neurobiological significance. In Study 2, the role of Apolipoprotein E (APOE) genotype was explored as a potential moderator of the relationship between dietary PUFA and cerebral metabolism. APOE is of special interest due to its critical role in lipid transport as well as its established status as a genetic risk factors for Alzheimer’s disease. Finally, Study 3 expanded the investigation of gene-diet interaction effects on brain function by examining the relationship between dietary PUFA and functional brain activity during a cognitive task, as well as the potential role of APOE genotype as a moderator of this relationship.

In sum, the proposed studies examined novel relationships between dietary nutrients and indices of brain function, and also explore the role of APOE genotype as a moderator of these associations. Identifying biomarkers associated with dietary effects in middle age is critical given that prevention is currently the most promising opportunity of intervention for dementia. Additionally, major implications of this work include potential for developing and augmenting dietary interventions that can be personalized according to genetic risk for AD.



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