Prospective study of bilingualism and cognitive reserve in the aging brain of Hispano adults with MCI - Project Summary Estimates from the Alzheimer's Association indicate that approximately one in ten older adults in the US have Alzheimer's disease (AD) while 15 to 20% have mild cognitive impairment (MCI), projecting that about a third of those will develop dementia within five years. Several variables have been associated with delaying the onset and rate of cognitive decline in AD and have been grouped under the Cognitive Reserve/ Resilience (CR/R) theory; it postulates that complex mental activity throughout the lifetime creates resistance to cognitive decline despite the biological risk (brain loss). Emerging evidence shows that bilingualism may be one of these neuroprotective factors in the aging brain, but results in bilingualism and CR/R remain inconsistent. Our objective is to analyze the contribution of bilingualism to CR/R in a large cohort of aging Spanish/English bilinguals and Spanish monolinguals with amnestic MCI (aMCI). To overcome limitations in previous research, we will use a longitudinal design, operational characterization of bilingualism, refined sociocultural measures, and multimodal neuroimaging. The current study will leverage and extend a large ongoing NIH cohort prospective study from the 1Florida Alzheimer's Disease Research Center (1Florida ADRC), in which Spanish/English bilingual Hispanics with aMCI are well-represented (n = 120), but Spanish monolinguals are underrepresented although they comprise approximately 40% of foreign-born Hispanics in the US. In the present study, we directly address this by deploying an intensive, culturally-informed, community-engaged research approach in the Miami area to increase outreach and recruit 120 Hispanic monolinguals with aMCI. We will make the ADRC MCI bilingual and monolingual groups ethnically equivalent and create a longitudinal data set (n=240), ensuring that we are well-powered to determine the contribution of bilingualism to CR in the aMCI population. As co-investigators on the 1Florida ADRC, our research team is well-positioned to execute the proposed study. We will collect neuropsychological data at years 1, 2, and 3 and neuroimaging data (MRI and DTI) at years 1 and 3. The neuropsychological battery will include the Loewenstein-Acevedo Scale for Semantic Interference and Learning (LASSI-L), a cognitive stress test that evaluates failure to recover from Proactive Semantic Interference (frPSI) and is highly sensitive to subtle cognitive changes in early AD. The innovation lies in studying the relationship between brain diffusivity measures of WM and frPSI, as measured by the LASSI-L in combination with volumetric brain data; the use of Bilingual indexes of language proficiency and degrees of acculturation, and levels of education. Our findings will advance our understanding of the complex interactions between neural, environmental, and sociocultural factors and the role of bilingualism in CR/R in AD/ADRD, paving the way for new targets for interventions and providing fundamental insight into the role of language(s) in the aging brain.