18 Vascular Risk, Cerebral White Matter, and Executive Functioning in Vietnam-Era Veterans with Traumatic Brain Injury and/or Post-Traumatic Stress Disorder: A Department of Defense Alzheimer’s Disease Initiative (DoD-ADNI) Study

• Published in: Journal of the International Neuropsychological Society 2023-11, Vol.29 (s1), p.127-128
• Main Authors: McGill, Makenna B, Clark, Alexandra L, Schnyer, David M
• Format: Article
• Language: English
• Subjects: Acquired Brain Injury (TBI/Cerebrovascular Injury & Disease - Adult); Aging; Alzheimer's disease; Amnesia; Anisotropy; Brain mapping; Cognitive ability; Consciousness; Dementia disorders; Diabetes; Diabetes mellitus; Executive function; Functional magnetic resonance imaging; Hypertension; Medical imaging; Military personnel; Neurodegenerative diseases; Neuroimaging; Obesity; Post traumatic stress disorder; Poster Session 02: Acute & Acquired Brain Injury; Statistical analysis; Substantia alba; Traumatic brain injury
• ISSN: 1355-6177; 1469-7661
• DOI: 10.1017/S1355617723002229

Objective:Research indicates that Veterans with a history of traumatic brain injury (TBI) are at increased risk for dementia. Although the precise mechanisms underlying this relationship are poorly understood, remote TBI may exacerbate normal age-related changes to cerebral white matter (WM) and result in cognitive decline. However, Veterans commonly experience a constellation of mental (e.g., post-traumatic stress disorder [PTSD] and depression) and vascular (e.g., diabetes, hypertension, obesity) health conditions that have also been implicated in pathologic cerebral WM and cognitive aging trajectories. Therefore, the present study sought to (1) clarify the effects of remote TBI within the context of PTSD, depression, and vascular risk on WM micro- and macrostructure, and (2) explore if WM integrity is associated with cognition in a sample of Vietnam-Era Veterans.Participants and Methods:The sample consisted of 195 male Veterans ages 60-80 (mean age=69.3) enrolled in the Department of Defense-Alzheimer’s Disease Neuroimaging Initiative (DoD-ADNI) study. 102 Veterans met criteria for TBI by sustaining a head-injury that resulted in a loss of consciousness, alteration of consciousness, or post-traumatic amnesia. Current and/or lifetime PTSD was designated by scores >30 on the Clinician-Administered PTSD Scale. The Geriatric Depression Scale was used as a continuous measure of depression. A vascular risk score (0-3) was calculated based on diabetes, hypertension, and obesity (BMI >30 kg/m2). An executive functioning composite was created by averaging sample-specific z-scores for Trail Making Tests (A and B), with higher scores indicating worse performance. Voxelwise analysis of WM microstructure (fractional anisotropy [FA]) was conducted with Tract-Based Spatial Statistics (TBSS), using non-parametric permutation testing with threshold-free cluster enhancement. SPM’s Lesion Segmentation Tool was used to investigate WM macrostructure (WM hyperintensity [WMH] volume). Lesion probability maps were masked to restrict WMH volume calculations to WM. Robust regression using M-estimation and predictive R2 calculated using 10-fold cross-validation examined WMH volume, predictor, and cognitive associations. Age was a covariate in all WM analyses, and education was a covariate in all cognitive analyses.Results:TBSS analysis revealed widespread, significant negative relationships between vascular risk and FA across numerous WM tracts (p’s