Project Summary/Abstract As the population ages, Latinx communities, families, and healthcare systems will be confronted by the growing crisis of Alzheimer's disease and related dementias (ADRD). Identifying factors that confer resilience to ADRD among aging Latinx communities is of critical importance to successfully reduce disparities. Some studies find that bilinguals are at reduced AD risk compared to monolinguals, but other studies do not find evidence of a bilingual advantage. Little attention has been given to within-group differences among bilinguals, such as age of second language (L2) acquisition, proficiency, and frequency of language use, and how these differences 1) are related to cognitive function in older age, 2) if they buffer the effects of neuropathology on cognitive decline, and 3) how cognitive decline in AD can influence language use among bilinguals. Determination of the aspects of bilingualism that confer resilience to AD could lead to novel interventions to mitigate cognitive aging and ADRD disparities. The overall aim of this proposed research is to determine whether aspects of bilingualism, including age of acquisition, language use, and proficiency, buffer the effects of neuroimaging markers of pathology (i.e., AD biomarkers and cerebrovascular disease) on cognition and cognitive decline within middle- and older-aged Latinx adults. The central hypothesis is that early age of L2 acquisition, greater daily use of both L1 and L2, and greater L2 proficiency will confer cognitive reserve, independent of confounding sociocultural factors (i.e., education, socioeconomic status, immigration). Aims 1a and 1b (K99) focus on identifying which aspects of bilingualism are associated with cognition and which moderate the relationship between imaging markers and cognition. Aims 2a and 2b (R00) proposes to determine the relationship between bilingualism and imaging markers on cognitive decline and determine whether change in cognitive status is associated with changes in bilingualism. The proposed study will harmonize data from Latinx adults currently enrolled in three longitudinal cohorts with available amyloid and tau PET, MRI, and cognitive assessments: the Offspring study and the Washington Heights-Inwood Columbia Aging Project at Columbia University, and the University of California-Davis Diversity Aging Cohort. To accomplish these goals, the applicant will build on his strengths in cultural neuropsychology, health disparities, and statistical methods by obtaining training during the K99 phase on 1) expanding knowledge of the cognitive neuroscience and psycholinguistics of bilingualism; 2) modeling neuroimaging data; 3) the operationalization and measurement of resilience among aging Latinx populations; and 4) enhancing statistical methods focused on data harmonization, casual inference methods and latent variable modeling. This K99/R00 proposal lays the foundation for an independent research career focused on mechanisms underlying the protective factors of bilingualism and biculturalism in cognitive aging in a diverse population.

PROJECT NARRATIVE. Latinx are at increased risk for Alzheimer's disease and related dementias (ADRD) compared with non- Hispanic whites. Bilingualism may reduce ADRD risk but prior studies lack detailed characterization of within- group differences among bilinguals such as age of second language (L2) acquisition, L2 proficiency, and frequency of dual language use and its relationship to cognition in the presence of neuropathology. The current study will elucidate mechanisms underlying the relationship among bilingualism, neuroimaging markers of pathology, and cognitive function, which has the potential to inform novel interventions to preserve cognitive function and reduce ADRD disparities.