Evidence map›Paper›PMID 38336728›Full record

ArticleJournal of neuroinflammation2024

Inflammatory biomarkers for neurobehavioral dysregulation in former American football players: findings from the DIAGNOSE CTE Research Project.

Suzan van Amerongen, Surya V Pulukuri, Fatima Tuz-Zahra, Yorghos Tripodis, Jonathan D Cherry, Charles Bernick, Yonas E Geda, Jennifer V Wethe, Douglas I Katz, Michael L Alosco and 15 more

Open access · goldAbstract read
In one paragraph

Article in Journal of neuroinflammation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
5.4field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 14 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors at 18 institutions in 4 countries.

Suzan van AmerongenBoston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Surya V PulukuriBoston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Fatima Tuz-ZahraDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Yorghos TripodisBoston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Jonathan D CherryBoston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Charles BernickCleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA.
Yonas E GedaDepartment of Neurology and the Franke Global Neuroscience Education Center, Barrow Neurological Institute, Phoenix, AZ, USA.
Jennifer V WetheDepartment of Psychiatry and Psychology, Mayo Clinic School of Medicine, Mayo Clinic Arizona, Scottsdale, AZ, USA.
Douglas I KatzBoston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Michael L AloscoBoston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Charles H AdlerDepartment of Neurology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale, AZ, USA.
Laura J BalcerDepartments of Neurology, Population Health and Ophthalmology, NYU Grossman School of Medicine, New York, NY, USA.
Nicholas J AshtonDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Kaj BlennowDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Daniel H DaneshvarDepartment of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, USA.
Elizabeth A ColasurdoVeterans Affairs Northwest Mental Illness Research, Education, and Clinical Center, Seattle, WA, USA.
Jeffrey J IliffVeterans Affairs Northwest Mental Illness Research, Education, and Clinical Center, Seattle, WA, USA.
Gail LiVeterans Affairs Northwest Mental Illness Research, Education, and Clinical Center, Seattle, WA, USA.
Elaine R PeskindVeterans Affairs Northwest Mental Illness Research, Education, and Clinical Center, Seattle, WA, USA.
Martha E Shenton *Psychiatry Neuroimaging Laboratory, Harvard Medical School, Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Boston, MA, USA.
Eric M Reiman *Banner Alzheimer's Institute, University of Arizona, Arizona State University, Translational Genomics Research Institute, and Arizona Alzheimer's Consortium, Phoenix, AZ, USA.
Jeffrey L Cummings *Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas, Las Vegas, NV, USA.
Robert A Stern *Boston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA. bobstern@bu.edu.
DIAGNOSE CTE Research Project Investigators
Boston University · USMayo Clinic in Arizona · USUniversity of Washington · USHarvard University · USNew York University · USBarrow Neurological Institute · USSahlgrenska University Hospital · SETranslational Genomics Research Institute · USUniversity of Gothenburg · SEUniversity of Nevada, Las Vegas · USAmsterdam UMC Location Vrije Universiteit Amsterdam · NLCleveland Clinic · USEncompass Health (United States)King's College London · GBLou Ruvo Brain Institute · USUK Dementia Research Institute · GBVA Boston Healthcare System · USVrije Universiteit Amsterdam · NL

Funding

Research Education ComponentP30AG072980 · NIA · BANNER HEALTH · PI ALIREZA ATRI · 2021 to 2026
$24.9M
Renewal of Centers of Biomedical Research Excellence (COBRE) (Phase 2) CNTN - ResubmissionP20GM109025 · NIGMS · CLEVELAND CLINIC FOUNDATION · PI JESSICA KIRKLAND CALDWELL · 2015 to 2026
$22.8M
Chronic Traumatic Encephalopathy: Detection, Diagnosis, Course, and Risk FactorsU01NS093334 · NINDS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI CUMMINGS, JEFFREY L., REIMAN, ERIC MICHAEL · 2016 to 2022
$17.0M
NIA NIH HHS P30 AG072980NIGMS NIH HHS P20 GM109025NIH HHS U01NS093334NINDS NIH HHS U01 NS093334
6 · The paper itself

Abstract

backgroundTraumatic encephalopathy syndrome (TES) is defined as the clinical manifestation of the neuropathological entity chronic traumatic encephalopathy (CTE). A core feature of TES is neurobehavioral dysregulation (NBD), a neuropsychiatric syndrome in repetitive head impact (RHI)-exposed individuals, characterized by a poor regulation of emotions/behavior. To discover biological correlates for NBD, we investigated the association between biomarkers of inflammation (interleukin (IL)-1β, IL-6, IL-8, IL-10, C-reactive protein (CRP), tumor necrosis factor (TNF)-α) in cerebrospinal fluid (CSF) and NBD symptoms in former American football players and unexposed individuals.

methodsOur cohort consisted of former American football players, with (n = 104) or without (n = 76) NBD diagnosis, as well as asymptomatic unexposed individuals (n = 55) from the DIAGNOSE CTE Research Project. Specific measures for NBD were derived (i.e., explosivity, emotional dyscontrol, impulsivity, affective lability, and a total NBD score) from a factor analysis of multiple self-report neuropsychiatric measures. Analyses of covariance tested differences in biomarker concentrations between the three groups. Within former football players, multivariable linear regression models assessed relationships among log-transformed inflammatory biomarkers, proxies for RHI exposure (total years of football, cumulative head impact index), and NBD factor scores, adjusted for relevant confounding variables. Sensitivity analyses tested (1) differences in age subgroups (< 60, ≥ 60 years); (2) whether associations could be identified with plasma inflammatory biomarkers; (3) associations between neurodegeneration and NBD, using plasma neurofilament light (NfL) chain protein; and (4) associations between biomarkers and cognitive performance to explore broader clinical symptoms related to TES.

resultsCSF IL-6 was higher in former American football players with NBD diagnosis compared to players without NBD. Furthermore, elevated levels of CSF IL-6 were significantly associated with higher emotional dyscontrol, affective lability, impulsivity, and total NBD scores. In older football players, plasma NfL was associated with higher emotional dyscontrol and impulsivity, but also with worse executive function and processing speed. Proxies for RHI exposure were not significantly associated with biomarker concentrations.

conclusionSpecific NBD symptoms in former American football players may result from multiple factors, including neuroinflammation and neurodegeneration. Future studies need to unravel the exact link between NBD and RHI exposure, including the role of other pathophysiological pathways.

Indexed as

Brain Injuries, TraumaticChronic Traumatic EncephalopathyFootballAgedBiomarkersHumansInterleukin-6Middle AgedBiomarkersInterleukin-6BiomarkersChronic traumatic encephalopathyCSFIL-6NeurodegenerationNeurofilament light chain proteinNeuroinflammationNeuropsychiatric symptomsRepetitive head impactsTraumatic encephalopathy syndrome

Identifiers

PMID38336728
PMCPMC10854026
OpenAlexW4391691934

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.