MRI-Visible Perivascular Spaces Associated With Cognitive Impairment in Military Veterans With Traumatic Brain Injury Mediated by CSF P-Tau

OBJECTIVE: To investigate the association of MRI-visible perivascular spaces (PVS) with cognitive impairment in military veterans with traumatic brain injury (TBI), and whether cerebrospinal fluid (CSF) p-tau and Aβ mediate this effect. MATERIALS AND METHODS: We included 55 Vietnam War veterans with a history of TBI and 52 non-TBI Vietnam War veterans from the Department of Defense Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. All the subjects had brain MRI, CSF p-tau, Aβ, and neuropsychological examinations. MRI-visible PVS number and grade were rated on MRI in the centrum semiovale (CSO-PVS) and basal ganglia (BG-PVS). Multiple linear regression was performed to assess the association between MRI-visible PVS and cognitive impairment and the interaction effect of TBI. Additionally, mediation effect of CSF biomarkers on the relationship between MRI-visible PVS and cognitive impairment was explored in TBI group. RESULTS: Compared with military control, TBI group had higher CSO-PVS number (p = 0.001), CSF p-tau (p = 0.022) and poorer performance in verbal memory (p = 0.022). High CSO-PVS number was associated with poor verbal memory in TBI group (β = -0.039, 95% CI −0.062, −0.016), but not in military control group (β = 0.019, 95% CI −0.004, 0.043) (p-interaction = 0.003). Further mediation analysis revealed that CSF p-tau had a significant indirect effect (β = −0.009, 95% CI: −0.022 −0.001, p = 0.001) and mediated 18.75% effect for the relationship between CSO-PVS and verbal memory in TBI group. CONCLUSION: MRI-visible CSO-PVS was more common in Vietnam War veterans with a history of TBI and was associated with poor verbal memory, mediated partially by CSF p-tau.