Single- versus two-test criteria for cognitive impairment: associations with CSF and imaging markers in former American football players
Bibliographic record
Abstract
Objective: Cognitive impairment is a core feature of traumatic encephalopathy syndrome (TES), the putative clinical syndrome of chronic traumatic encephalopathy—a neuropathological disease associated with repetitive head impacts (RHI). Careful operationalization of cognitive impairment is essential to improving the diagnostic specificity and accuracy of TES criteria. We compared single- versus two-test criteria for cognitive impairment in their associations with CSF and imaging biomarkers in male former American football players. Method: 169 participants from the DIAGNOSE CTE Research Project completed neuropsychological tests of memory and executive functioning. Cognitive impairment was identified by single-test criteria (z≤-1.5 on one test) and two-test criteria (z<-1 on two tests within a domain). ANCOVAs adjusting for age, race, education, body mass index, word-reading score, and APOE ε4 status assessed whether single- or two-test criteria predicted CSF markers (Aβ1-42, p-tau181, p-tau181/Aβ1-42, total tau, neurofilament light [NfL], glial fibrillary acidic protein [GFAP]) and MRI markers (hippocampal volume, cortical thickness, white matter hyperintensities). Results: Ninety-nine participants met single-test criteria for cognitive impairment. Sixty-six met two-test criteria. Participants who met two-test criteria had greater exposure to RHI than those who did not (p=.04). Two-test criteria were associated with higher CSF p-tau181/Aβ1-42 (q=.02) and CSF NfL (q=.02). The association between two-test criteria and CSF NfL remained after excluding amyloid-positive participants (q=.04). Single-test criteria were not associated with any biomarkers (q’s>.05). Conclusions: Two-test but not single-test criteria for cognitive impairment were associated with markers of neurodegeneration. Future clinical research in TES may benefit from applying two-test criteria to operationalize cognitive impairment.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".