Longitudinal White Matter Atrophy Predicts Cognitive Decline in Veterans, With Amplified Effects in Severe Posttraumatic Stress Disorder.

BACKGROUND

The integrity of cerebral white matter (WM) is critical for cognitive function and may decline in volume with age and trauma exposure, including posttraumatic stress disorder (PTSD). This study tested whether PTSD severity modifies the longitudinal relationships between age-related WM degeneration and cognitive change in veterans.

METHODS

A total of 297 post-9/11 veterans enrolled in the Translational Research Center for Traumatic Brain Injury and Stress Disorders (28 female, 269 male; ages 35 ± 10.1 years) were categorized using Clinician-Administered PTSD Scale scores, with scores ≥60 indicating severe PTSD (n = 92) and scores <60 indicating nonsevere PTSD (n = 205). Participants underwent structural brain magnetic resonance imaging and cognitive assessment of executive function, memory, and attention/processing speed at 2 time points approximately 2 years apart. General linear models examined the effects of age and PTSD severity on WM volume, cognitive function, and their interaction over time.

RESULTS

Widespread age-related WM atrophy was observed, with preliminary evidence of a greater decline in frontal and cingulate regions among veterans with severe PTSD. Although cognitive stability was observed over time, greater WM atrophy was associated with worsening executive function and attention/processing speed across several frontal regions. PTSD severity further amplified longitudinal brain-behavior relationships, with severe PTSD showing stronger associations between atrophy and declines in memory performance in a priori frontal regions. Exploratory effects of mild traumatic brain injury on age-related atrophy in severe PTSD were limited.

CONCLUSIONS

Severe PTSD amplifies the longitudinal cognitive consequences of age-related WM degeneration, even in the absence of overt cognitive decline. Veterans with severe PTSD may be at heightened risk for accelerated brain and cognitive aging.