PROJECT SUMMARY/ABSTRACT Each year in the United States, at least 2.8 million people sustain a traumatic brain injury (TBI) and 1.1% of the US population has lifelong disabilities as a consequence of TBI. Sustaining a moderate to severe TBI in middle age is associated with the acceleration of brain aging and increased risk of dementia. However, to date, there are no effective pharmacological agents for prevention or treatment of post-TBI cognitive deterioration. Conversely, mounting evidence suggests that aerobic exercise attenuates age-related cognitive decline linked to the preservation of brain tissue volume, white structural integrity, and cerebral perfusion. Our pilot study along with a few other small studies suggests that TBI persons may also benefit from aerobic exercise to improve cognitive function. Thus, a randomized controlled exercise clinical trial (RCT) is needed to provide evidence-based clinical decision-making regarding whether aerobic exercise training prevents or slows accelerated brain aging and cognitive decline after TBI. Therefore, the overarching goal of this proposal is to develop a study protocol to conduct a national multicenter exercise RCT assessing the efficacy of aerobic exercise training to improve cognitive function in mid-aged and older adults with moderate to severe TBI within the TBI model system (TBIMS) network (Primary outcome). We will address the following aims: Aim 1a: Identify potential barriers to exercise for middle-aged and older adults with moderate to severe TBI 1 year post-injury. We will conduct focus group and develop a survey to assess global neurocognitive function, and identify exercise barriers, as well as patterns of smartphone use among persons with moderate to severe TBI. Aim 1b: Develop a Personal Mobile Trainer ecosystem (PMT) to improve exercise compliance and reduce study burden. Using the Apple ResearchKit and CareKit, we will develop a cloud-based application – “PMT” to build in an individualized exercise-training protocol, collect exercise data, send reminders and video feedback, and conduct survey to improve the usability of PMT in persons with TBI. Aim 1c: Refine our individualized aerobic exercise- training program for persons with TBI in the North Texas TBIMS. We will: 1) tailor our exercise protocol to meet the individual needs of persons with TBI; 2) refine PMT based on participant’s feedback on the usability of the system. Aim 2: Establish the infrastructure to conduct a multicenter exercise RCT within the TBIMS. We will develop a RCT protocol, manual of operating procedures (MOP), establish the investigative team and define collaborative arrangements. This project will establish a solid infrastructure to conduct a phase II exercise RCT to promote regular aerobic exercise for improving brain health among middle aged and older adults with moderate to severe TBI.