Traumatic Brain Injury, Social Relationships, and Risk of Dementia - PROJECT SUMMARY/ABSTRACT Traumatic Brain Injury (TBI) is a significant public health concern, particularly among older individuals, and TBI affects everyone in an individual’s social network, not just the individual with the injury. Studies have shown that family members, particularly ones who take on the role of caregivers, may experience feelings of burden, psychological distress, anxiety and depression, and decreased quality of life. It is well demonstrated that TBI is a significant risk factor for Alzheimer’s disease and related dementias (ADRDs), and TBI is designated as one of fourteen potentially modifiable risk factors for dementia by the 2024 Lancet Commission on Dementia, along with social isolation. Cognitively stimulating activities, including social engagement, are also potentially modifiable and have been shown to be protective against dementia and mortality among older adults. However, the impact of interpersonal factors (e.g., social relationships) with respect to associations of TBI with dementia and mortality risk is not well-understood, particularly with consideration of potential differences by sex. Further, the impact of TBI on spouses/caregivers with respect to dementia and mortality risk is not clear. Examining neurodegenerative biomarkers in the context of TBI and social engagement has the potential to elucidate mechanisms underlying associations with dementia. This F32 application aligns squarely with NIA priority areas: 1) understanding the dynamics of aging via the effects of interpersonal factors, and 2) improving our understanding of the aging brain and ADRD, to inform interventions and policy. The overarching goal of this proposal is to examine the role of social relationships with respect to dementia risk both in the context of an aging individual with TBI and among spouses (as a surrogate for caregivers) of individuals who sustain a TBI. Aim 1 will investigate if measures of mid-life social engagement modify the association of later life TBI with dementia and neurodegenerative ADRD biomarker trajectories, and differences by sex. Aim 2 will evaluate whether an individual’s risk of dementia and neurodegenerative ADRD biomarker trajectories is associated with a spousal TBI event, further assessing differences by the occurrence of spouse mortality after TBI and by sex. This F32 will also support excellent professional and personal training opportunities for Dr. D’Alonzo in aging/dementia and the use of plasma biomarker and neuroimaging data in the context of epidemiologic studies under the guidance of an interdisciplinary team of expert mentors. The research and training plan will prepare her to become an independent investigator and aging/injury epidemiologist, implementing novel statistical methods focused on TBI across the life course and long-term cognitive and ADRD-relevant outcomes in older adults.