PROJECT SUMMARY/ABSTRACT The prevalence of Alzheimer’s disease and related dementias (ADRD) is projected to double over the next 20 years. Ethnic and racial minorities will bear a disproportionate burden of disease with the most staggering increase of nearly six-fold anticipated among Mexican Americans and other Hispanic groups. Nonetheless, there is marked variability in cognitive trajectories, and approximately two-thirds of Mexican Americans surviving into their 80’s will remain dementia-free. The variability in outcomes highlights the influence of risk and resilience factors, which may alter neurodegenerative disease course. Recent studies have suggested that upwards of 40% of all dementia cases may be attributable to potentially modifiable risk factors. Among these, the data supporting the protective benefits of lifestyle factors, such as physical, cognitive, and social activity engagement, are so compelling that the nation’s leading health organizations have adopted these findings as recommendations for attenuating ADRD risk. However, the protective effects of lifestyle factors in Mexican Americans, which may interact with socioeconomic factors, comorbid disease burden, genetic loading, and cultural factors, warrants further investigation. Assessment of activity engagement has typically relied on self- report, which is prone to inaccuracies due to the fallibility of memory, social desirability biases, and the limited frequency of evaluation, negating more nuanced understanding of behavioral change in response to common fluctuations in environmental and individual factors. Our team at Oregon Health & Science University has validated the Collaborative Aging Research using Technology (CART) platform, which is comprised of an integrated network of in-home monitoring devices that capture high-density multi-modal data and are coupled with algorithms to derive activity patterns that predict cognitive decline. Through a partnership with The University of Texas Health Science Center at San Antonio, we have extended the technology to the homes of 5 Mexican American older adults. We now propose to expand upon this line of research and leverage the CART platform to continuously monitor real-world physical, cognitive, and social activity patterns across a three-year period in a cohort of 120 older Mexican Americans adults (Aim 1a). We will further evaluate the modifying effects of socioeconomic status, acculturation, sex, depression, cardiovascular burden, and apolipoprotein ε4 status (Aim 1b). Next, we will explore the associations between activity engagement and traditional and novel neuroimaging indices of brain aging and ADRD (Aim 2). Finally, we will examine the inflammatory profile associated with activity engagement, as well as their associations with cognitive decline and neuroimaging outcomes (Aim 3). Leveraging the innovative CART technology platform, we will identify the activity engagement patterns that promote risk and resilience of cogniti...