Dietary Quality, Cognitive Decline and Brain Health in Puerto Rican Adults

PROJECT SUMMARYThe scientific premise of this proposal is that consumption of highly processed foods contributes to cognitivedecline with aging. These dietary effects may lead to health disparities in cognitive decline due to the knowngreater consumption of highly processed foods in low-income populations. While many factors are associatedwith the effects of a diet characterized by highly processed foods, including displacement of healthy foods andthe myriad of nutrients associated with these, we propose that two nutrients, in particular, may have effectsthrough known or emerging pathways that affect brain function. First, there is evidence that highly processedfoods contribute to greater intake of phosphorus (P) through P-based food additives which can increase food Pcontent by ≥70%. Vascular risk factors predict cognitive decline and excess P may elevate CVD risk. However,the role of P in cognitive decline remains unclear. One novel pathway is compensatory elevation in fibroblastgrowth factor 23 (FGF23), a predictor of vascular calcification and CVD. Klotho, a putative anti-aging factor,may be protective against CVD and cognitive decline. Among mice, a high P diet reduced klotho secretion.Excessive P consumption may lower klotho and impair cognitive function through modulation of FGF23, buthuman data remain sparse. P also elevates parathyroid hormone (PTH), which predicts CVD mortality andpresence of cerebral infarcts. Second, vitamin B6 (B6), a critical cofactor for ≥100 metabolic reactions, is easilylost with food processing and unlike other B vitamins is not added back to enriched grains. We have shownthat low B6 status was associated with inflammation, oxidative stress, metabolic syndrome, diabetes anddepressive symptoms in Puerto Rican adults. Earlier work with non-Hispanic white men, showed associationsof both diet and plasma B6 (pyridoxl-5'-phosphate,PLP) with 3 y cognitive decline. Latinos appear to bedisproportionately burdened by cognitive impairment compared to non-Hispanic whites. Moreover, recentevidence suggests that Puerto Ricans have >twice the odds of low global cognitive function compared toMexicans. With the growing and aging Latino population in the U.S likely to contribute to major increases in theburden of cognitive decline, it is critical that we improve our understanding of preventive risk factors that mayinform interventions. We will use data from the Boston Puerto Rican Health study (BPRHS), a longitudinalcohort study of U.S. mainland Puerto Ricans (45-74 y) with diet, nutritional biomarkers, and cognitive functiontesting data available at baseline and 2 and 5 y follow-up. We will recruit BPRHS participants to return (~ 8-yfrom baseline) for a repeat battery of cognitive exams and, for a subset, an MRI scan. We will quantify theassociations between processed foods consumption, P status (serum P, FGF23, klotho, and PTH), dietary B6,and PLP, as exposures, with ~8 y cognitive decline (psychometric testing) and brain structure, cerebralinfarcts, white matter integrity, and connectivity (MRI) at ~8 y, as outcomes. Further the potential mediativeroles of inflammation (CRP, IL-6, and TNF-α) and insulin resistance (HOMA-IR) will be measured.