To determine whether traumatic brain injury (TBI) history is associated with structural brain MRI differences in research participants with mild cognitive impairment (MCI).

TBI is a known risk factor for dementia. However, the relationship between prior TBI and structural brain changes in persons with prodromal dementia, i.e. MCI, remains unclear. Understanding this association would help inform risk stratification and treatment approaches in patients with MCI and history of TBI.

Subjects with Global Clinical Dementia Rating scores of 0.5 (indicating MCI) from the National Alzheimer's Coordinating Center dataset (September 2005-February 2025) were included. TBI status was delineated by whether participants had a history of TBI with loss of consciousness versus no TBI history. Analysis of covariance examined white matter hyperintensity, gray matter, and hippocampal volumes, controlling for age, sex, education, and cerebrum total cranial volume. To address covariate imbalances, a sensitivity analysis using 1:1 propensity score matching was performed.

Among 1,277 MCI patients (mean age 70 years, SD=7.7, range 46-95), 208 (16%) were in the TBI group. Groups differed significantly in age, sex, and cerebrum total cranial volumes. After covariate adjustment, no significant differences were observed for white matter hyperintensity (p=0.50), gray matter (p=0.50), or hippocampal (p=0.33) volumes, with negligible effect sizes (partial η²<0.001, Cohen's f<0.03). Propensity score matching successfully created 203 balanced pairs with standardized mean differences < 0.1 for all covariates. Results remained consistent with primary analysis (all p>0.37, Cohen's d<0.09). The study had > 94% power to detect small-to-medium effects (Cohen’s f = 0.10-0.25).

Structural brain MRI findings did not differ by TBI status in MCI patients after controlling for demographics and cerebrum total cranial volume. Results suggest prior TBI with loss of consciousness does not substantially contribute to volumetric brain changes beyond those already present in MCI. Limitations include reliance on self-reporting and heterogeneity in TBI characteristics.