PROJECT SUMMARY/ABSTRACT This is a K23 application for Dr. Dustin Hammers, Associate Professor and neuropsychologist at Indiana University pursuing patient-oriented clinical research on lifestyle interventions in Early-Onset Alzheimer’s Disease (EOAD). This K23 will provide him the means to strategically transition from clinician to independent investigator through targeted coursework, didactics and workshops, and career products. The candidate’s supportive and successful institutional environment ensures that the formal career development plan will add to his existing expertise in neurodegenerative disease. His long-term career goal is to become an independent clinician-scientist with an externally funded research program that will enhance behavioral treatment options for patients with EOAD. Despite expansion of research on interventions for Alzheimer’s disease (AD), treatment for patients diagnosed at a younger stage of life has been overlooked, due to the rareness of the condition and challenges identifying disease modifying treatments in traditional-onset AD. These patients experience a unique set of complications related to personal and occupational functioning, including cognitive declines while raising families and performing at the height of their careers. Identification of successful treatments for this condition would lead to significant improvements for patients and their families across multiple aspects of life. The purpose of this 5-year research plan is to collect preliminary data through an NIH-defined Stage IB (NIH Stage Model) study to investigate the feasibility and pilot testing of a lifestyle intervention on short-term and long-term cognition, functioning, and mood in participants with EOAD. Specific Aim 1 will evaluate the feasibility of a lifestyle intervention combining cognitive training and Tai Chi in participants with EOAD, testing the hypotheses that the experimental and active control groups will have comparable attrition rates, and that the combined intervention will be well-tolerated. Specific Aim 2 will investigate if this intervention improves cognitive, functional, and mood outcomes in participants with EOAD compared to an active control condition. It is hypothesized that participants undergoing intervention will perform better on outcomes compared to control participants both post-treatment and at 6-months follow-up. Specific Aim 3 will examine if training or clinical variables moderate benefit from this combined lifestyle intervention. It will explore whether a greater treatment response will be seen in women with EOAD relative to men, and if better response will be related to increased hours of training and decreased disease severity. Outcome improvement from this lifestyle intervention would enhance the personal/occupational functioning of patients with EOAD, have implications for healthcare practice, policy, and clinical trials, and inform this intervention for all forms of AD. The candidate’s training in a...