Evidence of increased brain amyloid in severe TBI survivors at 1, 12, and 24 months after injury: report of 2 cases

Abstract

Traumatic brain injury (TBI) is a major risk factor for Alzheimer’s disease. With respect to amyloid deposition, there are no published serial data regarding the deposition rate of amyloid throughout the brain after TBI. The authors conducted serial 18F-AV-45 (florbetapir F18) positron emission tomography (PET) imaging in 2 patients with severe TBI at 1, 12, and 24 months after injury. A total of 12 brain regions were surveyed for changes in amyloid levels. Case 1 involved a 50-year-old man who experienced a severe TBI. Compared with the 1-month time point, of the 12 brain regions that were surveyed, a decrease in amyloid (as indicated by standard uptake value ratios) was only observed in the hippocampus (−16%, left; −12%, right) and caudate nucleus (−18%, left; −18%, right), suggesting that initial amyloid accumulation in the brain was cleared between time points 1 and 12 months after injury. Compared to the scan at 1 year, a greater increase in amyloid (+15%) was observed in the right hippocampus at the 24-month time point. The patient in Case 2 was a 37-year-old man who suffered severe trauma to the head and a subsequent stroke; he had poor cognitive/functional outcomes and underwent 1.5 years of rehabilitation. Due to a large infarct area on the injured side of the brain (right side), the authors focused primarily on brain regions affected within the left hemisphere. Compared with the 1-month scan, they only found an increase in brain amyloid within the left anterior putamen (+11%) at 12 months after injury. In contrast, decreased amyloid burden was detected in the left caudate nucleus (−48%), occipital cortex (−21%), and precuneus (−19%) brain regions at the 12-month time point, which is indicative of early accumulation and subsequent clearance. In comparison with 12-month values, more clearance was observed, since a reduction in amyloid was found at 24 months after trauma within the left anterior putamen (−12%) and occipital cortex (−15%). Also, by 24 months, most of the amyloid had been cleared and the patient demonstrated improved results on the Rivermead symptom questionnaire, Glasgow Outcome Scale-Extended, and Disability Rating Scale. With respect to APOE status, the patient in Case 1 had two ε3 alleles and the patient in Case 2 had one ε2 and one ε3 allele. In comparison to the findings of the initial scan at 1 month after TBI, by 12 and 24 months after injury amyloid was cleared in some brain regions and increased in others. Serial imaging conducted here suggests that florbetapir F18 PET imaging may be useful in monitoring amyloid dynamics within specific brain regions following severe TBI and may be predictive of cognitive deficits.

The chronic and evolving neurological consequences of traumatic brain injury

“…PET) to identify neuropathological processes that might be activated following TBI, and could hence provide signatures for the cognate neurodegenerative diseases. Key processes that have started to be characterised in this context include amyloid deposition, [101][102][103][104][105] tau deposition, 104,106 and neuroinflammation. [107][108][109] Although the location and progress of pathology on MRI can provide useful clues to underlying neuropathology, the data from molecular imaging techniques provide insights that cannot be achieved even with advanced MRI.…”

<p>Spatial Patterns of Amyloid Deposition in Patients with Chronic Focal or Diffuse Traumatic Brain Injury Using ¹⁸F-FPYBF-2 PET</p>

“…The uptake of amyloid tracer 11 C-Pittsburgh compound B 11 C-PiB increases in all cortical gray matter and striatum in acute and chronic stages and in the posterior cingulate cortex in the chronic stage. 8,9 Other studies using 18 F-florbetapir have shown increased uptake in the frontal, temporal, and parietal cortices, striatum, and hippocampus in the chronic stage following TBI 10,11 . Sites of amyloid pathology are diverse in TBI populations because brain damage is usually spatially heterogeneous, depending on the injury type and its severity and the location of the impact.…”

Detection of brain amyloid‐β deposits due to the repetitive head trauma in a former karate player

“…Gatson et al . conducted serial amyloid PET imaging in two patients with severe TBI at 1, 12, and 24 months after injury and reported that within 2 years after severe TBI, amyloid had accumulated at both early and late time points . In contrast, Kawai et al .…”

“…1 Gatson et al conducted serial amyloid PET imaging in two patients with severe TBI at 1, 12, and 24 months after injury and reported that within 2 years after severe TBI, amyloid had accumulated at both early and late time points. 2 In contrast, Kawai et al examined 12 patients with posttraumatic neuropsychological impairment from the chronic stage to 10 years after TBI and reported that 11 C-labelled PiB was positive in three patients and negative in the other nine. 3 We ascribe the disagreements among these previous reports to the heterogeneity of the TBI-related neurodegenerative pathology.…”