Unveiling the link between glymphatic function and cortical microstructures in post-traumatic stress disorder

Abstract

PurposeThe discovery of the glymphatic system, crucial for cerebrospinal and interstitial fluid exchange, has enhanced our grasp of brain protein balance and its potential role in neurodegenerative disease prevention and therapy. Detecting early neurodegenerative shifts via noninvasive biomarkers could be key in identifying at-risk individuals for Alzheimer's disease (AD). Our research explores a diffusion tensor imaging (DTI) method that measures cortical mean diffusivity (cMD), potentially a more sensitive indicator of neurodegeneration than traditional macrostructural methods. Materials and methodsWe analyzed 67 post-traumatic stress disorder (PTSD)-diagnosed veterans from the Alzheimer's Disease Neuroimaging Initiative database. Participants underwent structural MRI, DTI, Aβ PET imaging, and cognitive testing. We focused on the DTI-ALPS technique to assess glymphatic function and its relation to cMD, cortical Aβ accumulation, and thickness, accounting for age and APOE ε4 allele variations. ResultsThe cohort, all male with an average age of 68.1 (SD 3.4), showed a strong inverse correlation between DTI-ALPS and cMD in AD-affected regions, especially in the entorhinal, parahippocampal, and fusiform areas. Higher DTI-ALPS readings were consistently linked with greater cortical thickness, independent of Aβ deposits and genetic risk factors. Age and cMD emerged as inversely proportional predictors of DTI-ALPS, indicating a complex interaction with age. ConclusionThe study confirms a meaningful association between glymphatic efficiency and cMD in AD-sensitive zones, accentuating cortical microstructural alterations in PTSD. It positions DTI-ALPS as a viable biomarker for assessing glymphatic function in PTSD, implicating changes in DTI-ALPS as indicative of glymphatic impairment.