Case Report of High-Stage Cortical-Sparing CTE in a Retired NFL Player with Frontal Hypometabolism and Progressive Cognitive Behavioral Decline

Introduction: Chronic traumatic encephalopathy (CTE) appears to represent a pathological outcome of significant repetitive head impact exposure. Although increasing clinicopathologic studies have characterized features of CTE during life, longitudinal prospective characterization integrating neuropsychological, neuroimaging, and neuropathological findings remains limited. Case Presentation: This report presents a 73-year-old retired National Football League (NFL) quarterback with CTE who developed behavioral problems in his 50s followed by cognitive decline that progressed until he was a danger to himself and others. Neuropsychological testing revealed moderate dysexecutive problems with anosognosia, significant encoding and recall deficits, and subtle deficits in language. FDG-PET revealed patchy hypometabolism most pronounced in the left prefrontal cortex with preservation of posterior cingulate metabolism. Pathological evaluation demonstrated widespread phosphorylated tau deposition diagnostic of high-stage cortical-sparing CTE, as well as limbic TDP-43 inclusions with hippocampal sclerosis. Conclusion: We present a case of a 73-year-old retired NFL quarterback in whom we prospectively recorded a rich history, neurological examination, neuropsychological testing, advanced imaging, and neuropathological evaluation. This case demonstrates a clear association between de novo behavioral and cognitive changes, neurometabolic abnormalities, and high-stage cortical-sparing CTE pathology.