TY - JOUR
T1 - Factors associated with subjective cognitive complaints in former American football players
AU - DIAGNOSE CTE Research Project
AU - Adler, Jennifer S.
AU - Ly, Monica T.
AU - Yhang, Eukyung
AU - Tripodis, Yorghos
AU - Adler, Charles H.
AU - Balcer, Laura J.
AU - Bernick, Charles
AU - Ashton, Nicholas
AU - Zetterberg, Henrik
AU - Blennow, Kaj
AU - Peskind, Elaine
AU - Banks, Sarah J.
AU - Barr, William B.
AU - Wethe, Jennifer V.
AU - Bondi, Mark W.
AU - Delano-Wood, Lisa
AU - Cantu, Robert C.
AU - Coleman, Michael J.
AU - Dodick, David W.
AU - Daneshvar, Daniel H.
AU - McClean, Michael D.
AU - Mez, Jesse
AU - Palmisano, Joseph N.
AU - Martin, Brett
AU - Lin, Alexander P.
AU - Koerte, Inga K.
AU - Bouix, Sylvain
AU - Cummings, Jeffrey L.
AU - Shenton, Martha E.
AU - Reiman, Eric M.
AU - Stern, Robert A.
AU - Alosco, Michael L.
N1 - Publisher Copyright:
© The Author(s), 2026. Published by Cambridge University Press on behalf of International Neuropsychological Society.
PY - 2026
Y1 - 2026
N2 - Objective: Subjective cognitive complaints (SCC) can precede cognitive decline and are associated with demographic, exposure, lifestyle, and psychological factors. Prevalences of SCC and their correlates in individuals with repetitive head impacts (RHI) are poorly understood. This study characterized SCC in former elite American football players by frequency, mood and behavioral correlates, concordance with informant reports, and associations with neuropsychological test performance, cerebrospinal fluid (CSF), and magnetic resonance imaging (MRI) markers of neurodegeneration. Method: Former American football players (n = 180) completed measures of global and domain-specific SCC, neuropsychiatric symptom questionnaires, neuropsychological testing, lumbar puncture, and MRI. Elastic net regression evaluated the relative importance of potential SCC correlates. Intraclass correlation coefficients measured concordance between self and informant reports. Multiple linear regressions tested associations between SCC and verbal memory and executive functioning scores. CSF Aβ1-42, p-tau181, t-tau, neurofilament light (NfL), hippocampal volume, and regional cortical thickness were examined for their potential associations with SCC. Results: Rates of SCC ranged from 43 to 77% depending on the domain. Symptoms of depression, impulsivity, and anxiety were strongly associated with SCC. Self- and informant-reported SCC showed moderate inter-rater agreement. Adjusting for age, race, education, APOE ϵ4 carrier status, and depressive symptoms, SCC were associated with lower objective verbal memory and executive functioning performance. SCC were associated with lower parahippocampal cortical thickness but not with hippocampal volume or any of the measured CSF tests. Conclusions: SCC are strongly associated with neuropsychiatric factors in former American football players. SCC may also be a marker of cognitive decline and neurodegeneration.
AB - Objective: Subjective cognitive complaints (SCC) can precede cognitive decline and are associated with demographic, exposure, lifestyle, and psychological factors. Prevalences of SCC and their correlates in individuals with repetitive head impacts (RHI) are poorly understood. This study characterized SCC in former elite American football players by frequency, mood and behavioral correlates, concordance with informant reports, and associations with neuropsychological test performance, cerebrospinal fluid (CSF), and magnetic resonance imaging (MRI) markers of neurodegeneration. Method: Former American football players (n = 180) completed measures of global and domain-specific SCC, neuropsychiatric symptom questionnaires, neuropsychological testing, lumbar puncture, and MRI. Elastic net regression evaluated the relative importance of potential SCC correlates. Intraclass correlation coefficients measured concordance between self and informant reports. Multiple linear regressions tested associations between SCC and verbal memory and executive functioning scores. CSF Aβ1-42, p-tau181, t-tau, neurofilament light (NfL), hippocampal volume, and regional cortical thickness were examined for their potential associations with SCC. Results: Rates of SCC ranged from 43 to 77% depending on the domain. Symptoms of depression, impulsivity, and anxiety were strongly associated with SCC. Self- and informant-reported SCC showed moderate inter-rater agreement. Adjusting for age, race, education, APOE ϵ4 carrier status, and depressive symptoms, SCC were associated with lower objective verbal memory and executive functioning performance. SCC were associated with lower parahippocampal cortical thickness but not with hippocampal volume or any of the measured CSF tests. Conclusions: SCC are strongly associated with neuropsychiatric factors in former American football players. SCC may also be a marker of cognitive decline and neurodegeneration.
KW - Alzheimer's disease
KW - cerebrospinal fluid
KW - chronic traumatic encephalopathy
KW - cognition
KW - neuropsychological testing
KW - repetitive head impact
UR - https://www.scopus.com/pages/publications/105031458608
U2 - 10.1017/S1355617726101866
DO - 10.1017/S1355617726101866
M3 - Journal Article
AN - SCOPUS:105031458608
SN - 1355-6177
JO - Journal of the International Neuropsychological Society
JF - Journal of the International Neuropsychological Society
ER -