UC San Diego

Background: Traumatic brain injury (TBI), multimorbidity, and lower social contact are associated with worse cognitive health outcomes among older adults. While greater social contact is associated with lower risk of dementia, it is unknown if aspects of social connection buffer the relationships of TBI or multimorbidity with cognitive and brain health in aging. Methods: This dissertation includes three studies. Using Vietnam Era Twin Study of Aging data, we tested prospective associations of TBI with cognitive performance trajectories in Study 1, and cross-sectional associations between TBI and markers of brain health in Study 2. In Study 3, we tested prospective associations of multimorbidity with cognitive performance trajectories in the Rancho Bernardo Study of Healthy Aging. In all studies, we tested for effect measure modification (EMM) by measures of social connectedness. Results: In Study 1, TBI was associated with greater decline in executive function, primarily among APOE ε4 carriers (β=-0.017; 95% CI=-0.033,-0.0019) compared to non-carriers (β=-0.0036; 95% CI=-0.013,0.0063; PInteraction=0.03). Relative to no TBI, TBI prior to military induction was associated with greater executive function decline (β=-0.011; 95% CI=-0.021,-7e-04). In Study 2, TBI was associated with microstructural differences in a white matter tract connecting occipital and temporal lobes, compared to no TBI (β=-0.017; SE=0.005; FDR-corrected p-value<0.01). There was no evidence of EMM by social connectedness (defined as loneliness) in Studies 1 or 2. In Study 3, multimorbidity was associated with faster declines in scores on the Mini-Mental State Examination (MMSE; β=-0.20; 95% CI=-0.35,-0.04), Trail-Making Test Part B (β=10.02; 95% CI=5.77,14.27), and Category Fluency (β=-0.42; 95% CI=-0.72,-0.13). There was EMM by social engagement; multimorbidity was associated with faster MMSE declines among those with low compared to medium or high social engagement (PInteraction<0.01). Conclusion: These results highlight the role of multimorbidity and remote TBI on cognitive health in aging. While our results do not support a buffering role of loneliness on effects of remote TBI on cognitive or brain health, they suggest that social engagement may support reducing adverse cognitive consequences of multimorbidity. These findings can inform efforts focused on increasing social contact to reduce cognitive decline and improve wellbeing, particularly among those with multimorbidity.