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Updated: Feb 10, 2026

Application of Granger Causality Analysis of the Directed Functional Connection in Alzheimer's Disease and Mild Cognitive Impairment
Published on: August 7, 2017
Traumatic brain injury history and progression from mild cognitive impairment to Alzheimer disease
Christian LoBue1, Fu L Woon2, Heidi C Rossetti1
1Department of Psychiatry, University of Texas Southwestern Medical Center.
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. (PsycINFO Database Record
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