PROJECT SUMMARY / ABSTRACT Bilingualism may protect against cognitive and brain changes in both healthy aging and Alzheimer’s disease and related dementias (ADRD) through enhanced executive functioning, arising from the need to constantly manage two or more languages. However, studies have yielded mixed results, and there remains an unknown role of bilingualism in 1) resistance to the development of neuropathology and in 2) resilience, the maintenance of cognition and/or brain structure in the presence of neuropathology burden. Further research to clarify the protective role of bilingualism in aging and ADRD is crucial and highly relevant, considering that over half of the world’s population and more than 20% of the US population speak two or more languages. This proposal will help clarify the role of bilingualism in healthy aging and in Alzheimer’s dementia (AD) by addressing the nuances underlying bilingualism, sociocultural factors, executive functioning, and dementia diagnoses. We hypothesize that bilingualism contributes to resistance and resilience through both network-specific (language and executive functioning) and domain-general effects, and its impact is moderated by bilingualism and sociocultural factors, type of executive functioning task, and AD variant. Our long-term goal is to develop a framework for bilingualism’s influence on resistance and resilience. We will leverage a well-characterized, prospectively studied cohort of monolingual and bilingual speakers at the UCSF Memory and Aging Center who span the range of healthy aging (N = 200) and AD variants (N = 400). This cohort is unique in its scope of longitudinal (2+ timepoints) neuropsychological, bilingualism/sociocultural, neuroimaging, and AD biomarker data. In Aim 1, we will determine which aspects of bilingualism contribute to a protective effect on executive functioning. We will group healthy aging and AD variant bilingual speakers based on bilingualism and sociocultural factors and assess for differences on cognitive measures and neuroimaging findings. In Aims 2 and 3, we will determine if bilingualism is associated with resistance and resilience by comparing monolingual and bilingual speakers within healthy aging and AD variant groups. We will test for differences between groups in grey matter (GM) volume and white matter (WM) integrity (Aim 2) and AD proteinopathy (Aim 3) and correlate the findings with performance on cognitive measures. We are well-suited to complete these aims given our exceptional multidisciplinary team with expertise in the neural underpinnings of language, clinical phenotyping of aging and AD, cognitive resilience, and multimodal imaging. Accomplishing these aims will significantly impact the field of ADRD research by give important insight into the neural basis of bilingualism and its influence on the trajectory of healthy aging and ADRD, thereby improving care for individuals with diverse language backgrounds.