PROJECT SUMMARY Latinos living in the 50 United States (US; hereinafter States), the largest racial/ethnic minority US population, are 1.5 times more likely to have Alzheimer’s disease than non-Latino whites. Latinos in the States exhibit unique profiles of Alzheimer’s disease and related dementias (ADRD) disparities across ethnic backgrounds (namely, Cubans, Dominicans, Mexicans, Puerto Ricans, and South and Central Americans). For example, Puerto Ricans are the Latino background with the lowest cognitive scores and highest prevalence of mild cognitive impairment and cardiovascular disease (CVD) risk factors-- long associated with higher ADRD risk. Thus, it is not surprising that ADRD is also a growing crisis among Latinos living in the US territory (island) of Puerto Rico (PR). In fact, the age-adjusted AD mortality rate in PR is double that of Latinos in the States. Unfortunately, research on protective factors that may serve as targets for promoting cognitive and brain health among Latinos in the States is scant and even less is known among Latinos in PR. As an early stage investigator, born and raised in PR, with doctoral training in community health sciences and post-doctoral training on CVD epidemiology, this K01 would the provide new skills and training in theories of resilience and reserve as well as content knowledge on normative cognitive aging, brain structure and neuroimaging, and protective factors for healthy aging. This K01 would also achieve the overall research goal of examining the mechanisms through which protective factors shown important in older non-Latino whites, i.e., favorable body composition, better psychological health, and higher levels of cognitive enrichment, support cognitive and brain health in middle-aged and older Latinos (ages 45+) with an emphasis on PR. Specifically, Aim 1 is focused on resilience to age; we will investigate baseline protective factors related with maintenance of cognitive function over a 7-year follow-up period (i.e., cognitive resilience to age) and examine whether protective factors modify the cross-sectional relation of age with brain structure (i.e., brain resilience to age) using previously collected data from the largest epidemiological study of Latino health in the States, the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Visits 1 and 2 and its NIA-funded SOL-INCA and SOL-INCA MRI ancillary studies. Aim 2 is focused on cognitive reserve; we will test whether protective factors modify the cross- sectional relations of brain structure with cognition by leveraging data from SOL-INCA MRI and SOL-INCA. Aim 3 is focused on PR, we will administer the HCHS/SOL cognitive battery in the NHLBI-funded PROSPECT cohort, an island-wide longitudinal epidemiological study of health, to estimate cognition and compare the protective factors-cognition relations between Puerto Ricans in PROSPECT and HCHS/SOL. This research is responsive to the priority areas of the NIA of identifying protec...