The effects of added sugar intake on brain blood flow and hippocampal function in midlife adults

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ABSTRACT Aging is the primary risk factor for Alzheimer's disease (AD) which is the most common form of dementia and among the fastest growing causes of morbidity and mortality in the United States. The risk factors for AD emerge during midlife and are similar to cardiovascular and cerebrovascular diseases. In this regard, stiffening of the large elastic arteries (i.e., the aorta and carotid arteries) and cerebral hypoperfusion occur with aging and are linked to age-related cognitive impairment, primarily through the transmission of damaging pressure waves to the cerebral vasculature, resulting in cerebrovascular dysfunction and neuronal damage. The impact of midlife vascular changes on the brain are further exacerbated by poor lifestyle habits, including the consumption of a diet that contains high amounts of added sugar (e.g., from ultra-processed foods containing high amounts of fructose). While the exact mechanisms are not known, a high sugar diet is associated with elevated plasma triglycerides (TGs), which may exacerbate age-related arterial dysfunction and memory impairment through a mechanism involving increased systemic inflammation. Our cross-sectional preliminary data suggest that plasma TGs are strongly associated with increased arterial stiffness, reduced cerebrovascular function, lower memory scores and decreased integrity of the hippocampus, a brain structure that is critical for encoding and recalling memories; however, it remains unknown how these factors are influenced by the consumption of added sugars. The purpose of this project is to establish preliminary evidence for a causal link between added sugar intake and adverse changes to vascular and brain health in midlife adults. Our central hypothesis is that excess added sugar intake causes reductions and hippocampal structure and function though adverse changes to arteries via a mechanism involving increased plasma TGs and systemic inflammation. We will conduct a randomized, single-blind, controlled-feeding study to determine the effects of consuming a diet containing low (5% of total energy intake) vs. high (25% of total energy intake) added sugar for 10-days each on measures of large elastic artery stiffness, cerebrovascular function and hippocampal structure and function. The expected outcome is evidence of a causal relation between added sugar intake and reductions in vascular and brain functions through a mechanism involving increased TG's and inflammation. The data generated from this project will support a future NIH R01 proposal for a randomized controlled trial aimed at lowering added sugar intake in mid-life adults.