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Traumatic Brain Injury Research · Journal article
JAMA Network Open · September 2, 2026
Early or partial results. Treat as a signal, not a conclusion.
This retrospective case series of 33 former NFL players with autopsy-confirmed CTE describes antemortem neuropsychological impairment patterns, with learning and memory most frequently affected (63%), followed by executive function (51.7%) and language (41.4%). Greater global phosphorylated tau burden was significantly associated with worse learning and memory performance, suggesting a neuropathologic correlate; however, the lack of a control group and small, highly selected sample limit the ability to establish diagnostic thresholds or generalize beyond professional football players.
Retrospective case series. Former National Football League players who underwent antemortem neuropsychological testing and had autopsy-confirmed chronic traumatic encephalopathy; 33 men with mean age at death 65.4 (SD 13.3) years; 25 with high-stage CTE and 8 with low-stage CTE.. Intervention: Antemortem neuropsychological evaluation with testing across cognitive domains (learning and memory, executive function, language, processing speed, visuospatial skills).. n = 33. Not stated in source..
Learning and memory impaired in 17 of 27 participants (63.0%) Executive function impaired in 15 of 29 participants (51.7%) Language impaired in 12 of 29 participants (41.4%)
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These findings characterize the expected antemortem neuropsychological signature of autopsy-confirmed CTE in former NFL players and demonstrate a link between tau pathology burden and memory impairment. However, the absence of a control group and restriction to professional athletes limit clinical utility for diagnostic accuracy or applicability to other populations with suspected CTE.
A retrospective case series of 33 autopsy-confirmed CTE cases describing antemortem neuropsychological profiles; no control group, no prospective design, and limited sample size restrict evidence strength despite addressing an important diagnostic question.
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These findings characterize the expected antemortem neuropsychological signature of autopsy-confirmed CTE in former NFL players and demonstrate a link between tau pathology burden and memory impairment. However, the absence of a control group and restriction to professional athletes limit clinical utility for diagnostic accuracy or applicability to other populations with suspected CTE.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Importance: Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with repetitive head impact exposure. CTE can only be diagnosed post mortem, and the antemortem neuropsychological profile is poorly understood, hindering accurate diagnosis before death. Objective: To characterize antemortem neuropsychological test performance of former National Football League (NFL) players with autopsy-confirmed CTE. Design, Setting, and Participants: This retrospective case series included former NFL players who completed an antemortem neuropsychological evaluation and had autopsy-confirmed CTE. Data were collected between January 1, 2017, and April 30, 2025. Statistical analysis was performed from September 2025 to June 2026. Exposure: CTE neuropathology, defined by the National Institute of Neurological Disorders and Stroke/National Institute of Biomedical Imaging and Bioengineering consensus panel. Main Outcomes and Measures: Neuropsychological test performance, neuropathologic diagnoses, and semiquantitative phosphorylated tau (p-tau) pathology across 11 brain regions were examined. Raw scores were converted to z scores using age, sex, and/or education level-based normative data. Test results with z scores of -1.5 or less were categorized as impaired; domains with 2 or more impaired test results were considered impaired. Results: The primary analytic sample included 33 men (mean [SD] age at death, 65.4 [13.3] years; mean [SD] time between testing and death, 2.4 [1.6] years), 25 with high- and 8 with low-stage CTE. Learning and memory was most impaired (17 of 27 [63.0%]), followed by executive function (15 of 29 [51.7%]) and language (12 of 29 [41.4%]). High-stage CTE participants generally had worse scores than low-stage CTE participants. Greater global p-tau burden was associated with worse learning and memory performance (B = -0.40; 95% CI, -0.70 to -0.09; P =.01). Findings were similar after excluding 9 participants with co-occurring Alzheimer disease or frontotemporal lobar degeneration tau. Conclusions and Relevance: In this retrospective case series of NFL players with autopsy-confirmed CTE, memory, executive function, and language impairments were common, and p-tau burden was associated with worse memory performance. Findings provide insight into the expected CTE neuropsychological profile and may help advance diagnosis before death.
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