Amyloid pathology fingerprint differentiates post-traumatic stress disorder and traumatic brain injury

Abstract

IntroductionTraumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are risk factors for early onset of Alzheimer's disease (AD) and may accelerate the progression rate of AD pathology. As amyloid-beta (Aβ) plaques are a hallmark of AD pathology, we hypothesized that TBI and PTSD might increase Aβ accumulation in the brain.MethodsWe examined PET and neuropsychological data from Vietnam War veterans compiled by the US Department of Defense Alzheimer's Disease Neuroimaging Initiative, to examine the spatial distribution of Aβ in male veterans' who had experienced a TBI and/or developed PTSD. Subjects were classified into controls, TBI only, PTSD only, and TBI with PTSD (TBI_PTSD) groups and data were analyzed using both voxel-based and ROI-based approaches.ResultsCompared to controls, all three clinical groups showed a pattern of mainly increased referenced standard uptake values (SUVR) for the amyloid tracer [18F]-AV45 PET, with rank order PTSD > TBI_PTSD > TBI > Control, and same rank order was seen in the deficits of cognitive functions. SUVR increase was observed in widespread cortical regions of the PTSD group; in white matter of the TBI_PTSD group; and cerebellum and precuneus area of the TBI group, in contrast with controls. The [18F]-AV45 SUVR correlated negatively with cerebrospinal fluid (CSF) amyloid levels and positively with the CSF tau concentrations.ConclusionThese results suggest that both TBI and PTSD are substantial risk factors for cognition decline and increased Aβ deposition resembling that in AD. In addition, both PTSD and TBI_PTSD have a different pathways of Aβ accumulation.

Functional connectivity dysfunction of insular subdivisions in cognitive impairment after acute mild traumatic brain injury

“…These brain areas are also known to be the site of the pathophysiological foundations of cognitive impairment caused by the early stages of the disease. Moreover, previous literature found notable accumulations of amyloid in the temporal gyrus in patients who sufferer with significant cognitive dysfunction which suggests partial reason why temporal gyrus is related to cognitive performance (Mohamed et al 2018). In addition, our study showed positive correlations between functional connectivity of insula and temporal gyrus and orientation score.…”

Incidence of mild cognitive impairment in World Trade Center responders: Long‐term consequences of re‐experiencing the events on 9/11/2001

“…These recalled stressful experiences are fairly common, with more than one‐quarter of WTC responders experiencing these symptoms more than a decade after the event [2]. Neuroimaging studies have reported that trauma survivors with chronic PTSD have more rapid hippocampal volume loss [10], reduced cortical thickness [11], increased β ‐amyloid deposition [9], and changes to plasma β ‐amyloid burden [39].…”

Tauopathy in veterans with long-term posttraumatic stress disorder and traumatic brain injury

“…Data acquisition procedures were standardized across all ADNI sites (information can be found at: http://adni.loni.usc.edu/wp-content/uploads/2015/02/01_DOD-ADNI_Tau-Addendum-Protocol_23Oct2014.pdf ). Data were preprocessed and analysed as described in our previous paper [ 25 ] using the FMRIB software library (FSL 5.0.9). MRI images were corrected for intensity inhomogeneity, skull-stripped, and segmented using the RECON-ALL [ 26 ] from Freesurfer.…”

“…To assess amyloid positivity, SUV maps of the amyloid [ 18 F]AV45 PET tracer from the same subjects were downloaded. The acquisition parameters were as described previously [ 25 ]. The [ 18 F]AV45 SUV maps were coregistered to individual T1-weighted MR images in native space using FSL-Flirt, and amyloid-PET SUVr values were calculated using the whole cerebellum as the reference region [ 22 ].…”