Memory loss was the most common deficit in NFL players with confirmed CTE

Chronic traumatic encephalopathy (CTE) can still only be diagnosed after death, by examining brain tissue. That leaves a hard question unanswered: what does the disease actually look like in a living person's thinking and memory? A case series published on 2 September in JAMA Network Open addresses it by matching former NFL players' cognitive tests, taken while they were alive, to what their autopsies later confirmed [s1].

What the researchers did

The study assembled former National Football League players who had completed a neuropsychological evaluation before death and had autopsy-confirmed CTE, with data collected between 1 January 2017 and 30 April 2025 [s1]. CTE neuropathology was defined by the consensus criteria of a US National Institutes of Health expert panel, and phosphorylated-tau (p-tau) pathology — the protein that accumulates in the disease — was scored across 11 brain regions [s1]. Raw test scores were converted to z-scores using normative data for age, sex and education; a test scoring 1.5 standard deviations or more below normal was counted as impaired, and a cognitive domain was counted impaired when two or more of its tests were [s1].

The primary sample was 33 men, with a mean age at death of 65.4 years and, on average, 2.4 years between their testing and their death [s1]. Twenty-five had high-stage CTE and eight had low-stage [s1].

What it found

Cognitive impairment clustered in specific domains. Learning and memory was the most commonly affected — impaired in 17 of 27 players tested (63.0%) — followed by executive function (15 of 29, 51.7%) and language (12 of 29, 41.4%) [s1]. Players with high-stage CTE generally scored worse than those with low-stage disease [s1].

The pathology tracked the deficits. 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) [s1]. That association held after excluding nine players who also had co-occurring Alzheimer disease or frontotemporal-lobar degeneration tau pathology — an important check, since those conditions damage memory too and could otherwise account for the link [s1].

What it does and does not establish

The value here is a clearer picture of the antemortem cognitive signature of confirmed CTE, drawn from cases where the diagnosis is certain rather than presumed [s1]. That is genuinely useful for building tools to identify the disease before death.

The limits are equally important, and mostly structural. This is a case series of 33 selected former professional players — men who came to brain banks, often because they or their families had concerns — so it describes what confirmed CTE looked like in this group, not how common CTE is, nor how reliably these test patterns would flag it in the living. There is no comparison group of players without CTE, so the profile cannot yet be turned into a diagnostic test; many conditions of ageing also impair memory and executive function. And a sample this size cannot support fine distinctions between subgroups.

Why it matters

CTE research has been dogged by the gap between a diagnosis that requires autopsy and the living patients who want answers. By anchoring cognitive findings to confirmed pathology, this study helps define what to look for — memory impairment foremost — and shows that tau burden and memory decline move together [s1]. Translating that into something that works prospectively, in living people and against a proper comparison group, remains the unfinished task.

This article is informational and does not constitute medical advice.

Sources

• [s1] Neuropsychological Profile of Autopsy-Confirmed Chronic Traumatic Encephalopathy. JAMA Network Open, 2 September 2026. https://doi.org/10.1001/jamanetworkopen.2026.31754