PROJECT SUMMARY—Caregiver Health and Attitudes in the Era of Therapeutic Discovery (Project E) In the era of frontotemporal dementia (FTD) therapeutic discovery, the primary focus will be on people with dementia (PWDs). However, the health and well-being of family and friends who serve as informal caregivers (CGs) will also be a major concern. CGs provide essential support for maintaining PWDs’ health and compensating for their functional declines, which differ considerably in FTD, Alzheimer’s disease (AD), and other dementias. Over time, these declines create additional burden that may adversely affect CGs’ health and, thus, their ability to provide high-quality care. CGs currently face difficult decisions about PWD participation in clinical trials. They will increasingly need to make decisions about using new therapeutics and be asked to help monitor PWD disease progression, treatment compliance, and treatment efficacy. Thus, the argument for integrating CGs for PWDs with a wide range of diagnoses into dementia research is compelling. Approach. From the new participants entering the PPG over the five-year project period, we will recruit a subsample of LMM PWD-CG dyads and NO functionally intact controls selected to maximize diversity in CG ethnicity, sex, and socioeconomic status (SES), and PWD diagnosis. Emotional functioning in CGs and PWD- CG dyads will be assessed initially in our Berkeley laboratory and repeated at two annual follow-ups conducted in participants’ homes. Combining these data with data from other PPG cores and projects, we will address two aims. Aim I: CG health. We will explore: (a) Trajectories. Characterize CG health trajectories and influences of moderators (i.e., PWD diagnosis; CG sex, ethnicity, and genetics); (b) Predictors. Determine associations between changes in PWD health and functioning, CG functioning, and external resources and changes in CG health and influences of moderators; (c) Mediator. Determine how changes in the PWD-CG relationship explain associations between predictors and changes in CG health; and (d) Optimal measures. Determine optimal measures (observational measures; self, clinician, and informant ratings) for predicting changes in CG health. Aim L: CG attitudes towards trials and therapeutics. Paralleling Aim L, we will explore: (a) Trajectories. Characterize CG attitude trajectories and influences of moderators (i.e., PWD diagnosis; CG sex, ethnicity, genetics); (b) Predictors. Determine associations between changes in PWD health and functioning, CG functioning, and external resources and changes in CG attitudes and influences of moderators; (c) Mediator. Determine how changes in the PWD-CG relationship explain associations between predictors and changes in CG attitudes; and (d) Optimal measures. Determine optimal measures for predicting changes in CG attitudes toward trials and therapeutics. Significance. Research findings from Project E can inform future efforts to assess risk in CGs and desi...