FORMER NFL players with autopsy-confirmed chronic traumatic encephalopathy have shown a distinct neuropsychological profile dominated by learning, memory, and executive function impairment, a case series study has found.
Chronic traumatic encephalopathy can only be diagnosed after death, and its antemortem neuropsychological profile has remained poorly understood, hindering accurate diagnosis during life. Researchers have therefore characterised neuropsychological test performance among former National Football League players with confirmed chronic traumatic encephalopathy at autopsy.
This retrospective case series included former NFL players who completed antemortem neuropsychological evaluation and had autopsy-confirmed chronic traumatic encephalopathy, defined using National Institute of Neurological Disorders and Stroke and National Institute of Biomedical Imaging and Bioengineering consensus criteria. Data were collected between January 2017 and April 2025, with statistical analysis conducted from September 2025 to June 2026.
Neuropsychological test scores were converted to z scores using age, sex, and education-based norms, with impairment defined as a z score of −1.5 or lower, and domains with two or more impaired tests classified as impaired. Semiquantitative phosphorylated tau pathology was assessed across 11 brain regions.
The primary sample comprised 33 men (mean age at death 65.4 years, SD 13.3; mean time between testing and death 2.4 years, SD 1.6), including 25 with high-stage and 8 with low-stage disease.
Learning and memory was the most impaired domain (17 of 27, 63.0%), followed by executive function (15 of 29, 51.7%) and language (12 of 29, 41.4%). High-stage disease was generally associated with worse performance than low-stage disease. Greater global phosphorylated tau burden was associated with worse learning and memory performance (B −0.40, 95% CI −0.70 to −0.09, P=.01). Findings remained similar after excluding nine participants with co-occurring Alzheimer disease or frontotemporal lobar degeneration tau pathology.
These findings have provided insight into the expected neuropsychological profile of chronic traumatic encephalopathy, potentially advancing diagnosis before death. As the largest study of its kind to combine standardised antemortem testing with neuropathologic confirmation, it has strengthened evidence linking p-tau burden to objective cognitive performance, though the modest sample and exclusively former NFL cohort mean findings may not generalise to other populations exposed to repetitive head impacts.
Reference
Aaronson A et al. Neuropsychological profile of autopsy-confirmed chronic traumatic encephalopathy. JAMA Netw Open. 2026;9(9):e2631754.
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