Neuroimaging Biomarkers of Chronic Traumatic Encephalopathy: Targets for the Academic Memory Disorders Clinic

Abstract

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts, such as those from contact sports. The pathognomonic lesion for CTE is the perivascular accumulation of hyper-phosphorylated tau in neurons and other cell process at the depths of sulci. CTE cannot be diagnosed during life at this time, limiting research on risk factors, mechanisms, epidemiology, and treatment. There is an urgent need for in vivo biomarkers that can accurately detect CTE and differentiate it from other neurological disorders. Neuroimaging is an integral component of the clinical evaluation of neurodegenerative diseases and will likely aid in diagnosing CTE during life. In this qualitative review, we present the current evidence on neuroimaging biomarkers for CTE with a focus on molecular, structural, and functional modalities routinely used as part of a dementia evaluation. Supporting imaging-pathological correlation studies are also presented. We targeted neuroimaging studies of living participants at high risk for CTE (e.g., aging former elite American football players, fighters). We conclude that an optimal tau PET radiotracer with high affinity for the 3R/4R neurofibrillary tangles in CTE has not yet been identified. Amyloid PET scans have tended to be negative. Converging structural and functional imaging evidence together with neuropathological evidence show frontotemporal and medial temporal lobe neurodegeneration, and increased likelihood for a cavum septum pellucidum. The literature offers promising neuroimaging biomarker targets of CTE, but it is limited by cross-sectional studies of small samples where the presence of underlying CTE is unknown. Imaging-pathological correlation studies will be important for the development and validation of neuroimaging biomarkers of CTE.