Decreased DTI-APLS correlated with cognitive impairment in Veterans with post-traumatic stress disorder

Abstract: Post-traumatic stress disorder (PTSD) is a risk for cognitive impairment with underlying mechanism unresolved. Our study aimed to evaluate the glymphatic function in veterans with post-traumatic stress disorder (PTSD), and to explore associations between glymphatic function, sleep patterns, cerebrospinal fluid (CSF) biomarkers (Aβ, t-tau, p-tau), and cognitive impairment. In our study, we included 43 Vietnam War veterans with PTSD and 43 controls. Diffusion tensor image analysis along the perivascular space (DTI-ALPS) was calculated to reflect glymphatic function. Multiple linear regressions and mediation analyses were employed to examine the relationships between the clinician-administered PTSD scale (CAPS) scores, Pittsburgh Sleep Quality Index (PSQI), DTI-ALPS and cognitive impairment. Our study revealed that PTSD group exhibited lower DTI-ALPS (p = 0.001), higher CAPS (p < 0.001), higher PSQI (p < 0.001), and poorer cognitive performance in CDR-SoB (p = 0.019) and ADAS-Cog total 13 (p = 0.009). CAPS was significantly associated with DTI-ALPS (β = -0.0018, 95% CI: -0.0029, -0.0006, p = 0.0028). PSQI demonstrated an indirect effect (β = -0.0005, 95% CI: -0.0011, -0.0001) and mediated 21.74% effect for the relationship between CAPS and DTI-ALPS. CAPS was significantly associated with CDR-SoB and ADAS-Cog total 13 (β = 0.0067, 95% CI: 0.00087, 0.0124, p = 0.024; β = 0.058, 95% CI: 0.013, 0.103, p = 0.012). DTI-ALPS had an indirect effect (β = 0.0024, 95% CI: 0.0006, 0.0069) and mediated all effect for the relationship between CAPS and CDR-SoB. In conclusion, glymphatic system was impaired in PTSD veterans revealed by DTI-ALPS, and poor sleep quality partially mediated the relationship between PTSD severity and impaired glymphatic function. DTI-ALPS mediated the relationship between PTSD severity and cognitive impairment.