The effects of traumatic brain Injury, post-traumatic stress disorder on Amyloid-β associated network hyperconnectivity and progression of gray matter atrophy

Abstract

Background

Amyloid-β associated network hypersynchrony is an early manifestation of pre-clinical Alzheimer’s Disease (AD). The overall goal was to investigate a. how TBI and PTSD influence hypersynchrony expression and b. how progressing gray matter atrophy affects hypersynchrony expression.

Methods

T1-weighted images, resting-state fMRIs and amyloid-β SUVRs were obtained from 234 DoD-ADNI subjects with or without TBI and/or PTSD. The denoised BOLD signal from 382 rois was extracted with CONN and dynamic resting state analysis was used to identify 8 states including one corresponding to a hypersynchrony state (HSS). SuStaIn with gray matter volumes and amyloid-β SUVR as inputs was used to identify 2 subtypes with progressive gray matter loss.

Results

HSS dwell-time correlated positively with amyloid-β (Kendall tau = 0.125,p = 0.047) and tau Braak stage 5&6 SUVR (Kendall tau = 0.200,p = 0.035). TBI increased the likelihood to observe the HSS (81 % with vs. 18 % wo TBI p < 0.001) as did a diagnosis of PTSD (67.4 % with vs. 32.6 % wo PTSD, p = 0.003). The SuStaIn subtypes differed mostly by the timing of the amyloid-β build-up but not by atrophy pattern. Subtype 2 had higher amyloid-β loads and longer HSS dwell-times than subtype 1 that had higher CAPS scores than subtype 2. Gray matter atrophy did not influence HSS dwell-time.

Conclusion

TBI and PTSD increased the likelihood to observe HSS. HSS dwell time was determined by AD pathology severity. The subtype characteristics indicate that PTSD drives gray matter loss in subtype 1 and AD pathology that in subtype 2. Severity of gray matter atrophy influenced neither HSS occurrence nor intensity.