Single- versus two-test criteria for cognitive impairment: associations with CSF and imaging markers in former American football players

 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 improvi...

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Published in:Clinical neuropsychologist 2025-01, p.1-25
Main Authors: Ly, Monica T, Altaras, Caroline, Tripodis, Yorghos, Adler, Charles H, Balcer, Laura J, Bernick, Charles, Zetterberg, Henrik, Blennow, Kaj, Peskind, Elaine R, Banks, Sarah J, Barr, William B, Wethe, Jennifer V, Lenio, Steve, Bondi, Mark W, Delano-Wood, Lisa M, Cantu, Robert C, Coleman, Michael J, Dodick, David W, Mez, Jesse, Daneshvar, Daniel H, Palmisano, Joseph N, Martin, Brett, Lin, Alexander P, Koerte, Inga K, Bouix, Sylvain, Cummings, Jeffrey L, Reiman, Eric M, Shenton, Martha E, Stern, Robert A, Alosco, Michael L
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Language:English
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axonal injury
Clinical Medicine
cognitive impairment
Klinisk medicin
neurodegeneration
repeated head trauma
repetitive head impact
traumatic encephalopathy syndrome
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container_title Clinical neuropsychologist
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creator Ly, Monica T
Altaras, Caroline
Tripodis, Yorghos
Adler, Charles H
Balcer, Laura J
Bernick, Charles
Zetterberg, Henrik
Blennow, Kaj
Peskind, Elaine R
Banks, Sarah J
Barr, William B
Wethe, Jennifer V
Lenio, Steve
Bondi, Mark W
Delano-Wood, Lisa M
Cantu, Robert C
Coleman, Michael J
Dodick, David W
Mez, Jesse
Daneshvar, Daniel H
Palmisano, Joseph N
Martin, Brett
Lin, Alexander P
Koerte, Inga K
Bouix, Sylvain
Cummings, Jeffrey L
Reiman, Eric M
Shenton, Martha E
Stern, Robert A
Alosco, Michael L
description  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.  169 participants from the DIAGNOSE CTE Research Project completed neuropsychological tests of memory and executive functioning. Cognitive impairment was identified by single-test criteria ( ≤-1.5 on one test) and two-test criteria (
doi_str_mv 10.1080/13854046.2025.2451828
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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.  169 participants from the DIAGNOSE CTE Research Project completed neuropsychological tests of memory and executive functioning. Cognitive impairment was identified by single-test criteria ( ≤-1.5 on one test) and two-test criteria ( &lt;-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 (Aβ , p-tau , p-tau /Aβ , total tau, neurofilament light [NfL], glial fibrillary acidic protein [GFAP]) and MRI markers (hippocampal volume, cortical thickness, white matter hyperintensities). 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 ( =.04). Two-test criteria were -associated with higher CSF p-tau /Aβ ( =.02) and CSF NfL ( =.02). The association between two-test criteria and CSF NfL remained after excluding amyloid-positive participants ( =.04). Single-test criteria were not associated with any biomarkers ( 's&gt;.05).  Two-test but not single-test criteria for cognitive impairment were associated with markers of neurodegeneration. 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subjects axonal injury
Clinical Medicine
cognitive impairment
Klinisk medicin
neurodegeneration
repeated head trauma
repetitive head impact
traumatic encephalopathy syndrome
title Single- versus two-test criteria for cognitive impairment: associations with CSF and imaging markers in former American football players
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