Tauopathy PET and amyloid PET in the diagnosis of chronic traumatic encephalopathies: studies of a retired NFL player and of a man with FTD and a severe head injury

Abstract

Single, severe traumatic brain injury (TBI) which elevates CNS amyloid, increases the risk of Alzheimer's disease (AD); while repetitive concussive and subconcussive events as observed in athletes and military personnel, may increase the risk of chronic traumatic encephalopathy (CTE). We describe two clinical cases, one with a history of multiple concussions during a career in the National Football League (NFL) and the second with frontotemporal dementia and a single, severe TBI. Both patients presented with cognitive decline and underwent [18F]-Florbetapir positron emission tomography (PET) imaging for amyloid plaques; the retired NFL player also underwent [18F]-T807 PET imaging, a new ligand binding to tau, the main constituent of neurofibrillary tangles (NFT). Case 1, the former NFL player, was 71 years old when he presented with memory impairment and a clinical profile highly similar to AD. [18F]-Florbetapir PET imaging was negative, essentially excluding AD as a diagnosis. CTE was suspected clinically, and [18F]-T807 PET imaging revealed striatal and nigral [18F]-T807 retention consistent with the presence of tauopathy. Case 2 was a 56-year-old man with personality changes and cognitive decline who had sustained a fall complicated by a subdural hematoma. At 1 year post injury, [18F]-Florbetapir PET imaging was negative for an AD pattern of amyloid accumulation in this subject. Focal [18F]-Florbetapir retention was noted at the site of impact. In case 1, amyloid imaging provided improved diagnostic accuracy where standard clinical and laboratory criteria were inadequate. In that same case, tau imaging with [18F]-T807 revealed a subcortical tauopathy that we interpret as a novel form of CTE with a distribution of tauopathy that mimics, to some extent, that of progressive supranuclear palsy (PSP), despite a clinical presentation of amnesia without any movement disorder complaints or signs. A key distinguishing feature is that our patient presented with hippocampal involvement, which is more frequently seen in CTE than in PSP. In case 2, focal [18F]-Florbetapir retention at the site of injury in an otherwise negative scan suggests focal amyloid aggregation. In each of these complex cases, a combination of [18F]-fluorodeoxyglucose, [18F]-Florbetapir and/or [18F]-T807 PET molecular imaging improved the accuracy of diagnosis and prevented inappropriate interventions.

Mind the gaps—advancing research into short-term and long-term neuropsychological outcomes of youth sports-related concussions

“…PET scanning could enable paediatric patients to be monitored for the presence and persistence of acute post-concussion amyloid, and to determine whether scan positivity and negativity predict different outcomes. 176,177 Other PET imaging agents with potential utility in paedi atric populations include new tracers that bind neurofibrillary tangles composed of tau. Early imaging results with 18 F-T807, 18 F-T808 and 18 F-THK5105 are proving to be useful in confirming the presence of tauopathy in various clinical situations, including AD.…”

“…181 In addition, a recent report contains the first description of tauopathy imaging in a living person with suspected sports-associated CTE. 177 Given the extent of chronic tau pathology in concussion, repetitive subconcussive injury and CTE, tau tracers may be useful as diagnostic and prognostic biomarkers (for example, to distinguish CNI from CTE). Studies with these tracers in adults with CTE are underway, but their use in paediatric populations will depend on future research to determine whether tau pathology is present in young patients after TBI or concussion.…”

Sports-related brain injuries: connecting pathology to diagnosis

“…93 This patient had a clinical suspicion of CTE given his career history and an insidious onset of memory and cognitive impairments. PET imaging revealed striatal and nigral 18 F-T807 retention consistent with the presence of tauopathy in these areas; however, postmortem evaluation of pathology was not performed, which limited the ability to directly correlate pathological findings with clinical symptoms and PET findings.…”

184 Interrelationships Among Neuroimaging Biomarkers, Neuropsychological Test Data, and Symptom Reporting in a Cohort of Retired National Football League Players

“…68 Functional MRI can evaluate brain activity in the acute and chronic phases of injury, 1,54,69 and positron emission tomography (PET) can identify protein structures, such as amyloid plaques, which may be suggestive of ongoing neurodegeneration. 47 Utilizing these advanced neuroimaging techniques, several studies have correlated positive neuroimaging findings (thought to result from cumulative RBT) with neurocognitive decline. 23,33,59,66,67,74 As a result, it has become widely accepted that RBT leads to structural brain pathology, which in turn can serve as either an in vivo or postmortem biomarker for clinical diagnoses of abnormal neurobehavioral changes or neurocognitive decline.…”