Association Between Traumatic Brain Injury and Cognitive Decline Among Middle-to-Older Aged Men in the Vietnam Era Twin Study of Aging.

Traumatic brain injury (TBI) is associated with increased risk of dementia. However, whether TBI is associated with greater cognitive decline over time in specific cognitive domains among older adults is not well understood. This prospective cohort study used data from 1476 male Vietnam Era Twin Study of Aging participants (average age at study entry = 57.9 years, range = 51-71 years; 97.6% non-Hispanic; 92.5% White) collected from 2003 to 2019, who had complete information on prior TBI. Participants completed a comprehensive neuropsychological assessment at up to three visits over up to a 12-year follow-up period during which they also self-reported their history of TBI. Multivariable, linear mixed-effects models were used to assess associations between TBI and cognitive performance trajectories. Effect measure modification by apolipoprotein E (APOE) epsilon 4 (ε4) genotype status was assessed in a subset of participants. Thirty-one percent of participants reported a history of TBI; 29.4% were APOE ε4 carriers. There were no statistically significant associations of TBI with decline in episodic memory, executive function, or processing speed among participants overall. In models stratified by APOE ε4 carrier status, TBI was associated with a larger magnitude of decline in executive function for APOE ε4 carriers (β = -0.0181; 95% confidence interval [CI] -0.0335, -0.0027) compared to noncarriers (β = -0.0031; 95% CI -0.0128, 0.0067; P _Interaction = 0.03). In sensitivity analyses, TBI earlier in life (before military induction, average age = 20 years) was associated with faster declines in executive function compared to no TBI, irrespective of APOE ε4 status. In this sample of middle-to-older aged men, TBI was associated with faster declines in executive function among APOE ε4 carriers and among those who reported TBI in early life. These findings support the importance of a life course perspective when considering factors that may influence cognitive health in aging.