PROJECT ABSTRACT As the world ages, Alzheimer’s Disease (AD) and related dementias are quickly becoming some of the most pernicious and burdensome diseases around the globe. This burden is particularly high for Latinx older adults, who have a higher risk of developing AD, and exhibit age-related cognitive decline earlier and with more severe dementia symptoms than non-Latinx Whites. Despite these known disparities, the Latinx community continues to be significantly under-represented in AD research. Toward this end, preliminary evidence suggests that mindfulness-based programs (MBPs) – which refer to training of mindfulness meditation skills in group-based settings – may help prevent AD in at-risk Latinx individuals. Indeed, MBPs have been found to improve cognitive health and psychological well-being by addressing major AD risk factors (e.g., chronic stress, depression), and as such, have significant potential as a low-cost and scalable lifestyle intervention to reduce AD vulnerability. However, a significant challenge to further research in this area is that the traditional curricular format of MBPs may not be applicable, relevant, or accessible to Latinx older adults, due to language and cultural barriers, as well as disparities in access to health care. The goal of this R61 proposal is to address this challenge by evaluating the feasibility and effectiveness of a culturally-adapted MBP that is sensitive to the specific needs of the Latinx older adult community. To achieve this goal, we fully leverage the complementary expertise of our investigative team, drawing on the extensive experience and strong community partnerships forged by co-PI Parra Perez in adapting mindfulness-based stress reduction (the most widely utilized MBP) for use with Spanish-speaking immigrant communities, by further refining the curriculum to be targeted towards Latinx older adults. We rigorously examine the MBP intervention, in terms of effectiveness and key mechanisms of action, drawing upon cutting-edge advances in the cognitive neuroscience of aging and mindfulness science, by utilizing a powerful new experimental design strategy developed by co-PI Braver with post- doctoral fellow Lin. Specifically, we utilize a longitudinal EEG protocol to test whether enhanced engagement of a focused attention mindfulness state is selectively related to neurocognitive benefits, while monitoring the translation of mindfulness into daily-life contexts through an Ecological Momentary Assessment (EMA) protocol delivered via a customized mobile application designed specifically for use with Spanish-speaking Latinx older adults. Finally, we test for the role of preclinical AD and related neurodegeneration in moderating MBP-related benefits, using state-of-the-art blood plasma-based biomarkers to assess AD risk with low cost and participant burden. This proposed project is a direct response to recurrent calls for prioritizing the creation and dissemination of culturally informed research approaches and programs for Latinx populations. The study will provide a rich set of preliminary pilot data that can be used to inform a subsequent early-stage clinical trial at reducing AD prevalence/burden within the Latinx community.

PROJECT NARRATIVE Alzheimer’s Disease (AD) is an incurable neurodegenerative condition that causes immense human suffering and economic burden that may be especially pernicious for Latinx older adults. The proposed research will examine the feasibility and effectiveness of a new mindfulness training program designed specifically for this community, in terms of its ability to reduce the risk for AD by enhancing cognitive health and psychological well- being. This project directly addresses a major public health prerogative and holds high impact potential to yield valuable new tools for mitigating the risk of AD in communities that may be particularly vulnerable.