Project Summary / Abstract Alzheimer’s Disease (AD) and Alzheimer's Disease-Related Dementias (ADRD) not only exact a heavy toll on patients, they also impose an enormous emotional, physical, and financial burden on unpaid, often family, caregivers. The strain of providing care for a loved one diagnosed with AD, often across several years, is associated with elevated depression risk and poorer overall health. Existing cognitive and behavioral intervention approaches for ADRD unpaid primary caregivers operate via biobehavioral mechanisms that remain to be clarified. In addition, existing interventions target many components and strategies simultaneously, making inferences about the effectiveness of particular strategies difficult to draw, and involve substantial time/cost burdens. Emotion regulation skills represent an ideal target for psychological intervention to promote healthy coping in ADRD caregivers. The proposed research seeks to use an experimental medicine approach to test the efficacy and biobehavioral mechanisms of a novel, relatively brief, targeted, scalable, entirely smartphone-based cognitive emotion regulation intervention aimed at improving psychological outcomes (i.e., reducing perceived stress, caregiver burden, and depressive symptoms) in ADRD unpaid primary caregivers as well as examine potential benefits of the caregiver intervention on quality of life in care recipients. Cognitive reappraisal (i.e., the ability to modify the trajectory of an emotional response by thinking about and appraising emotional information in an alternative, more adaptive way) represents a highly promising target for psychological intervention in ADRD caregivers. Reappraisal can be operationalized via two primary tactics: psychological distancing (i.e. appraising an emotional stimulus as an objective, impartial observer) and reinterpretation (i.e., imagining a better outcome than what initially seemed apparent). The proposed project builds upon promising preliminary work to investigate the efficacy and underlying biobehavioral mechanisms of a novel, one-week cognitive reappraisal intervention in this population, with follow-up assessments at 2 weeks, 4 weeks, and 3 months. ADRD unpaid primary caregivers will be randomly assigned to receive training in either distancing, reinterpretation, or a no regulation natural history control condition, with ecological momentary assessments of self-reported positive and negative affect, remotely- collected psychophysiological health-related biomarkers (i.e., heart rate variability data measured using smartphone-based photoplethysmography), and health-related questionnaire reports. The proposed study aims to mechanistically relate changes in psychological and psychophysiological function to prediction of health-relevant behavioral outcomes during a novel emotion regulation intervention never before implemented in this stressed, high risk group.