title: Neuroinflammation and brain atrophy in former NFL players: An in vivo multimodal imaging pilot study.
abstract: There are growing concerns about potential delayed, neuropsychiatric consequences (e.g, cognitive decline, mood or anxiety disorders) of sports-related traumatic brain injury (TBI). Autopsy studies of brains from a limited number of former athletes have described characteristic, pathologic changes of chronic traumatic encephalopathy (CTE) leading to questions about the relationship between these pathologic and the neuropsychiatric disturbances seen in former athletes. Research in this area will depend on in vivo methods that characterize molecular changes in the brain, linking CTE and other sports-related pathologies with delayed emergence of neuropsychiatric symptoms. In this pilot project we studied former National Football League (NFL) players using new neuroimaging techniques and clinical measures of cognitive functioning. We hypothesized that former NFL players would show molecular and structural changes in medial temporal and parietal lobe structures as well as specific cognitive deficits, namely those of verbal learning and memory. We observed a significant increase in binding of [(11)C]DPA-713 to the translocator protein (TSPO), a marker of brain injury and repair, in several brain regions, such as the supramarginal gyrus and right amygdala, in 9 former NFL players compared to 9 age-matched, healthy controls. We also observed significant atrophy of the right hippocampus. Finally, we report that these same former players had varied performance on a test of verbal learning and memory, suggesting that these molecular and pathologic changes may play a role in cognitive decline. These results suggest that localized brain injury and repair, indicated by increased [(11)C]DPA-713 binding to TSPO, may be linked to history of NFL play. [(11)C]DPA-713 PET is a promising new tool that can be used in future study design to examine further the relationship between TSPO expression in brain injury and repair, selective regional brain atrophy, and the potential link to deficits in verbal learning and memory after NFL play.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Coughlin
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Yuchuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA.|Department of Neurology, Johns Hopkins Medical Institutions,Baltimore, MD, USA.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Munro
authors.affiliation: Department of Health Sciences Informatics, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Shuangchao
authors.initials: S
authors.lastname: Ma
authors.affiliation: Department of Biostatistics, Johns Hopkins Medical Institutions,Baltimore, MD, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Yue
authors.affiliation: Department of Biostatistics, Johns Hopkins Medical Institutions,Baltimore, MD, USA.
authors.forename: Shaojie
authors.initials: S
authors.lastname: Chen
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Raag
authors.initials: R
authors.lastname: Airan
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Pearl K
authors.initials: PK
authors.lastname: Kim
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Ashley V
authors.initials: AV
authors.lastname: Adams
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Cinthya
authors.initials: C
authors.lastname: Garcia
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Higgs
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Haris I
authors.initials: HI
authors.lastname: Sair
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Akira
authors.initials: A
authors.lastname: Sawa
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Gwenn
authors.initials: G
authors.lastname: Smith
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Constantine G
authors.initials: CG
authors.lastname: Lyketsos
authors.affiliation: Department of Biostatistics, Johns Hopkins Medical Institutions,Baltimore, MD, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Caffo
authors.affiliation: School of Chemistry, The University of Sydney, NSW 2006, Sydney, Australia.|Discipline of Medical Radiation Sciences, The University of Sydney, NSW 2006, Sydney, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Kassiou
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA.
authors.forename: Tomas R
authors.initials: TR
authors.lastname: Guilarte
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA.|Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
mesh_terms: D000081:Acetamides; D000368:Aged; D056352:Athletes; D001284:Atrophy; D001921:Brain / Q000276:immunology* / Q000473:pathology*; D002250:Carbon Radioisotopes; D005538:Football; D060005:Genotyping Techniques; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D009483:Neuropsychological Tests; D009929:Organ Size; D010865:Pilot Projects; D049268:Positron-Emission Tomography; D011720:Pyrazoles; D011743:Pyrimidines; D019275:Radiopharmaceuticals
chemical_list: D000081:Acetamides; D002250:Carbon Radioisotopes; C507091:N,N-diethyl-2-(2-(4-methoxyphenyl)-5,7-dimethyl-pyrazolo(1,5-a)pyrimidin-3-yl)-acetamide; D011720:Pyrazoles; D011743:Pyrimidines; D019275:Radiopharmaceuticals
keywords: Microglia; Mild traumatic brain injury; Molecular neuroimaging; Neuroinflammation; Translocator protein