Abstract Deficits in cognitive control are at the core of much cognitive decline experienced by many older adults, often leading to functional decline and eventually dementia. The rapidly growing segment of the population facing such cognitive decline has the potential to negatively impact society broadly and it has been estimated that maintaining or improving cognition in older adults (OA) could potentially prevent or delay the onset of an estimated 10 million new cases of Alzheimer’s disease and other dementias. Given the lack of success in discovering effective pharmacological or preventative therapies to prevent dementias, developing targeted interventions to remediate cognitive deficits is vital. To this end, we developed a novel closed-loop, digital meditation intervention (MediTrain) that was designed to improve regulation of focused attention in healthy OA. In a mechanistic RCT, we recently showed that MediTrain lead to broad improvements in cognitive control, with the greatest gains seen in a subgroup of OA with cognitive deficits (i.e., MCI-like). In addition, this intervention led to reduced stress reactivity and improvements in cellular markers of aging. A goal of this proposal will be to extend the scope of our intervention by conducting a mobile RCT (mRCT) in a large sample, recruited nationally, who will complete the study entirely on mobile devices, providing the statistical power to perform planned moderator and subgroup analyses to understand the sources of variability in treatment response. Another important question that emerged from our initial RCT of MediTrain in OA was: what is the minimal and/or optimal dose of the intervention required to achieve the benefits we observed? Thus, this proposed research will tackle two specific aims: First, we will conduct in a large, mRCT of MediTrain in OA at varying doses of treatment to determine the minimum effective dose required for cognitive improvement and stress reduction. Second, we will examine the moderating effect of cognitive decline on treatment effects. We will also include an exploratory aim to examine the impact of potential genetic (Alzheimer’s polygenic hazard scores), physiological (cardiovascular risk), and social (race/ethnicity) moderators on the treatment effects. To accomplish these aims, we will conduct a large-scale mRCT of MediTrain deployed on mobile devices in a diverse, nation-wide sample of OA (N = 3240), who will complete the study entirely on mobile devices. This large, national cohort will provide the sample size necessary to examine individual and subgroup differences in treatment response across a diverse swath of the general population. All participants will complete baseline, immediate follow-up, and 6-month follow-up assessments of cognitive and functional outcomes. We anticipate that this unique methodological approach and experimental design will significantly advance the development of treatment programs directed at the broad range of cognitive ab...