PROJECT SUMMARY The goal of this renewal of the Social Networks and Alzheimer’s Disease study (R01 AG057739) is to understand the social and biological mechanisms underlying the role of social connectedness in mild cognitive impairment (MCI) and Alzheimer’s disease and related dementias (ADRD). This longitudinal study leverages a cohort of older adults with early stage ADRD, MCI, and age- matched cognitively normal controls (N=609) established in 2015 and followed annually through 2023. The SNAD study features high dimensional characterization of personal social networks, relationships, environments, and activities obtained via in-home interviews, integrating these data with clinical consensus diagnosis, extensive cognitive testing, genotyping, and functional and structural neuroimaging data collected annually through the NIA-sponsored Indiana Alzheimer’s Disease Research Center. Findings from SNAD reveal robust and extensive cognitive and neurological benefits of social bridging, or access to an expansive and diverse set of loosely connected individuals. As a form of cognitive enrichment, social bridging may be protective of cognitive decline through the development of cognitive reserve (CR), or cognitive adaptability that buffers the impact of brain pathology on cognitive function. In addition to producing novel insights, SNAD raised new research questions and revealed data limitations that necessitate a second project period and additional longitudinal follow up. In the next phase of the study, we propose to increase sample size and extend the follow-up period, increase racial and socioeconomic diversity in the cohort, and collect additional data on stress exposures over the life course to test novel mechanisms through stress pathways. Aim 1 is to conduct long-term follow-ups of the SNAD cohort to examine longitudinal relationships between personal social network dynamics, neurodegenerative changes, and clinical conversion to MCI or ADRD. Aim 2 is to diversify the SNAD cohort to determine whether observed associations between social network characteristics and clinical cognitive decline are replicable in communities at high risk for ADRD. Aim 3 is to explore mediating and moderating relationships between social network characteristics, stress exposures, and cognitive decline. The SNAD study is interdisciplinary, combining leading-edge methods from the social and biomedical sciences, and leveraging the resources of funded centers for ADRD, neuroimaging, and sociomedical sciences. By increasing our understanding of the links between biological and social processes, this project may help identify novel targets for intervention to reduce the burden of ADRD on individuals, families, and the health care system.