Traumatic Brain Injury History and Progression from Mild Cognitive Impairment to Alzheimer Disease

Objective: To examine whether history of traumatic brain injury (TBI) is associated with more rapid progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Method: Data from 2,719 subjects with MCI were obtained from the National Alzheimer's Coordinating Center. TBI was categorized based on presence (TBI+) or absence (TBI-) of reported TBI with loss of consciousness (LOC) without chronic deficit occurring >1 year prior to diagnosis of MCI. Survival analyses were used to determine if a history of TBI predicted progression from MCI to AD up to 8 years. Random regression models were used to examine whether TBI history also predicted rate of decline on the Clinical Dementia Rating scale Sum of Boxes score (CDR-SB) among subjects who progress to AD. Results: Across 8 years, TBI history was not significantly associated with progression from MCI to a diagnosis of AD in unadjusted (HR = 0.80; 95% CI [0.63, 1.01]; p = .06) and adjusted (p = .15) models. Similarly, a history of TBI was a nonsignificant predictor for rate of decline on CDR-SB among subjects who progressed to AD (b = 0.15, p = .38). MCI was, however, diagnosed a mean of 2.6 years earlier (p < .001) in TBI+ subjects compared with the TBI- group. Conclusions: A history of TBI with LOC was not associated with progression from MCI to AD, but was linked to an earlier age of MCI diagnosis. These findings add to a growing literature suggesting that TBI might reduce the threshold for onset of MCI and certain neurodegenerative conditions, but appears unrelated to progression from MCI to AD. General Scientific Summary A history of traumatic brain injury might contribute to a neurodegenerative process by slightly accelerating its onset for some individuals, but appears unrelated to subsequent decline. This is contrary to what would be expected if a brain injury somehow triggers the progressive development of a neurodegenerative disease. However, further research is needed, as the effects of injury severity and age at time of injury are unknown.