Project Summary/Abstract The epidemic of Alzheimer’s disease and associated cognitive decline is a critical public health challenge that will grow as the US and world populations age. US Latinos, and particularly Puerto Ricans, suffer a disproportionate burden: Puerto Ricans are at approximately double the risk of Alzheimer’s disease compared to non-Hispanic whites. Increasing evidence points to the bi-directional communication between the brain and the gut microbiome--the gut-microbiome-brain-axis--as an important factor in brain health. Despite the promising nature of this field, limited research has been done on the association between the microbiome and cognition, particularly in minority populations. Mapping the relationship between the gut microbiome and cognition in vulnerable populations such as US-based Puerto Ricans, with excess Alzheimer disease, is key to addressing current and preventing future health disparities. The proposed project will be the largest study in a minority population to date, and the first in Puerto Ricans, on the role of the gut microbiome in cognitive decline. The proposed study will leverage an established cohort--the Boston Puerto Rican Health Study (BPRHS), a longitudinal cohort with 1499 participants at baseline, three completed waves of cognitive assessments, recent MRI, and extensive covariate data. This project will develop a framework of how the human gut microbiome multi-omics contributes to cognitive trajectory and markers of AD/ADRD in Latinos. It will leverage previously collected stool samples, MRI, and 14 years of longitudinally collected data on cognition and covariates among participants of the BPRHS. Key strengths of this proposal include: 1) leverage of a large, NIH-funded prospective study of Boston area Puerto Ricans (P01AG023394, P50HL105185, R01AG055948), an underserved and understudied minority population 2) validated and updated prospective data on cognitive decline, MRI, dietary and lifestyle covariates 3) the interdisciplinary expertise of the research team, including chronic disease epidemiology, community-based research, cognition, the microbiome, MRI and predictive modeling. This study will have a strong translational impact, enabling future microbiome-targeted interventions to promote cognitive health and will contribute to the development of tools needed for a preclinical diagnosis and/or treatment of cognitive decline and Alzheimer’s disease among this vulnerable population.

Project Narrative Our appreciation of the impact of the gut microbiome on brain health, including Alzheimer’s disease and cognitive decline, is in the early stages. This study will be the first to examine the gut microbiome multi-omics in relation to cognitive decline in a Puerto Rican population, and the first in a minority population, and validate in two independent external cohorts. This project will advance our understanding of how the human gut microbiome contributes to the pathophysiology of Alzheimer’s disease and cognitive decline and will contribute to the development of tools needed for a preclinical diagnosis and/or treatment and to addressing health disparities in Alzheimer’s disease.