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Neuroimaging of cognitive dysfunction and depression in aging retired National Football League players: a cross-sectional study.

ABSTRACT: OBJECTIVES To assess cognitive impairment and depression in aging former professional football (National Football League [NFL]) players and to identify neuroimaging correlates of these dysfunctions. DESIGN We compared former NFL players with cognitive impairment and depression, cognitively normal retired players who were not depressed, and matched healthy control subjects. SETTING Research center in the North Texas region of the United States. PATIENTS Cross-sectional sample of former NFL players with and without a history of concussion recruited from the North Texas region and age-, education-, and IQ-matched controls. Thirty-four retired NFL players (mean age, 61.8 years) underwent neurological and neuropsychological assessment. A subset of 26 players also underwent detailed neuroimaging; imaging data in this subset were compared with imaging data acquired in 26 healthy matched controls. MAIN OUTCOME MEASURES Neuropsychological measures, clinical diagnoses of depression, neuroimaging mea-sures of white matter pathology, and a measure of cerebral blood flow. RESULTS Of the 34 former NFL players, 20 were cognitively normal. Four were diagnosed as having a fixed cognitive deficit; 8, mild cognitive impairment; 2, dementia; and 8, depression. Of the subgroup in whom neuroimaging data were acquired, cognitively impaired participants showed the greatest deficits on tests of naming, word finding, and visual/verbal episodic memory. We found significant differences in white matter abnormalities in cognitively impaired and depressed retired players compared with their respective controls. Regional blood flow differences in the cognitively impaired group (left temporal pole, inferior parietal lobule, and superior temporal gyrus) corresponded to regions associated with impaired neurocognitive performance (problems with memory, naming, and word finding). CONCLUSIONS Cognitive deficits and depression appear to be more common in aging former NFL players compared with healthy controls. These deficits are correlated with white matter abnormalities and changes in regional cerebral blood flow.

SUBMITTER: Hart J

PROVIDER: S-EPMC4016798 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Neuroimaging of cognitive dysfunction and depression in aging retired National Football League players: a cross-sectional study.

Hart John J Kraut Michael A MA Womack Kyle B KB Strain Jeremy J Didehbani Nyaz N Bartz Elizabeth E Conover Heather H Mansinghani Sethesh S Lu Hanzhang H Cullum C Munro CM

JAMA neurology 20130301 3

OBJECTIVES To assess cognitive impairment and depression in aging former professional football (National Football League [NFL]) players and to identify neuroimaging correlates of these dysfunctions. DESIGN We compared former NFL players with cognitive impairment and depression, cognitively normal retired players who were not depressed, and matched healthy control subjects. SETTING Research center in the North Texas region of the United States. PATIENTS Cross-sectional sample of former NFL player ...[more]

PMID: 23303193

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Project description:Importance:Microglia, the resident immune cells of the central nervous system, play an important role in the brain's response to injury and neurodegenerative processes. It has been proposed that prolonged microglial activation occurs after single and repeated traumatic brain injury, possibly through sports-related concussive and subconcussive injuries. Limited in vivo brain imaging studies months to years after individuals experience a single moderate to severe traumatic brain injury suggest widespread persistent microglial activation, but there has been little study of persistent glial cell activity in brains of athletes with sports-related traumatic brain injury. Objective:To measure translocator protein 18 kDa (TSPO), a marker of activated glial cell response, in a cohort of National Football League (NFL) players and control participants, and to report measures of white matter integrity. Design, Setting, and Participants:This cross-sectional, case-control study included young active (n?=?4) or former (n?=?10) NFL players recruited from across the United States, and 16 age-, sex-, highest educational level-, and body mass index-matched control participants. This study was conducted at an academic research institution in Baltimore, Maryland, from January 29, 2015, to February 18, 2016. Main Outcomes and Measures:Positron emission tomography-based regional measures of TSPO using [11C]DPA-713, diffusion tensor imaging measures of regional white matter integrity, regional volumes on structural magnetic resonance imaging, and neuropsychological performance. Results:The mean (SD) ages of the 14 NFL participants and 16 control participants were 31.3 (6.1) years and 27.6 (4.9) years, respectively. Players reported a mean (SD) of 7.0 (6.4) years (range, 1-21 years) since the last self-reported concussion. Using [11C]DPA-713 positron emission tomographic data from 12 active or former NFL players and 11 matched control participants, the NFL players showed higher total distribution volume in 8 of the 12 brain regions examined (P?<?.004). We also observed limited change in white matter fractional anisotropy and mean diffusivity in 13 players compared with 15 control participants. In contrast, these young players did not differ from control participants in regional brain volumes or in neuropsychological performance. Conclusions and Relevance:The results suggest that localized brain injury and repair, indicated by higher TSPO signal and white matter changes, may be associated with NFL play. Further study is needed to confirm these findings and to determine whether TSPO signal and white matter changes in young NFL athletes are related to later onset of neuropsychiatric symptoms.

Project description:BackgroundChronic traumatic encephalopathy (CTE) is a neurodegenerative disease that has been associated with a history of repetitive head impacts. The neuropathological diagnosis is based on a specific pattern of tau deposition with minimal amyloid-beta deposition that differs from other disorders, including Alzheimer's disease. The feasibility of detecting tau and amyloid deposition in the brains of living persons at risk for CTE has not been well studied.MethodsWe used flortaucipir positron-emission tomography (PET) and florbetapir PET to measure deposition of tau and amyloid-beta, respectively, in the brains of former National Football League (NFL) players with cognitive and neuropsychiatric symptoms and in asymptomatic men with no history of traumatic brain injury. Automated image-analysis algorithms were used to compare the regional tau standardized uptake value ratio (SUVR, the ratio of radioactivity in a cerebral region to that in the cerebellum as a reference) between the two groups and to explore the associations of SUVR with symptom severity and with years of football play in the former-player group.ResultsA total of 26 former players and 31 controls were included in the analysis. The mean flortaucipir SUVR was higher among former players than among controls in three regions of the brain: bilateral superior frontal (1.09 vs. 0.98; adjusted mean difference, 0.13; 95% confidence interval [CI], 0.06 to 0.20; P<0.001), bilateral medial temporal (1.23 vs. 1.12; adjusted mean difference, 0.13; 95% CI, 0.05 to 0.21; P<0.001), and left parietal (1.12 vs. 1.01; adjusted mean difference, 0.12; 95% CI, 0.05 to 0.20; P = 0.002). In exploratory analyses, the correlation coefficients in these three regions between the SUVRs and years of play were 0.58 (95% CI, 0.25 to 0.79), 0.45 (95% CI, 0.07 to 0.71), and 0.50 (95% CI, 0.14 to 0.74), respectively. There was no association between tau deposition and scores on cognitive and neuropsychiatric tests. Only one former player had levels of amyloid-beta deposition similar to those in persons with Alzheimer's disease.ConclusionsA group of living former NFL players with cognitive and neuropsychiatric symptoms had higher tau levels measured by PET than controls in brain regions that are affected by CTE and did not have elevated amyloid-beta levels. Further studies are needed to determine whether elevated CTE-associated tau can be detected in individual persons. (Funded by Avid Radiopharmaceuticals and others.).

Project description:ImportanceLong-term adverse health outcomes, particularly those associated with repetitive head impacts, are of growing concern among US-style football players in the US and Canada.ObjectiveTo assess whether exposure to repetitive head impacts during a professional football career is associated with an increase in the risk of all-cause mortality.Design, setting, and participantsThis retrospective cohort study included 13 912 players in the 1969 to 2017 National Football League (NFL) seasons. All cause-mortality up until July 1, 2018, was included. Data collection was performed from July 13, 2017, to July 1, 2018, as reported in the Pro Football Reference.ExposuresThe main exposure was a professional football cumulative head impact index (pfCHII). The pfCHII was measured by combining cumulative padded practice time and games played summed during seasons of play reported in the Pro Football Reference and a player position risk adjustment from helmet accelerometer studies.Main outcomes and measuresDemographic characteristics except for the pfCHII were calculated for 14 366 players with complete follow-up. The pfCHII was calculated for 13 912 players (eliminating the 454 specials teams players). Cox proportional hazards regression was used to compare hazard ratios (HRs) of death by repetitive head impacts. Analyses were unadjusted and adjusted for birth year, body mass index, and height.ResultsAmong 14 366 NFL players who had follow-up for analysis, the mean (SD) age was 47.3 (14.8) years, the mean (SD) body mass index was 29.6 (3.9), and 763 of 14 366 players (5.3%) had died. Among 13 912 players in the pfCHII analysis, the median pfCHII was 32.63 (interquartile range, 13.71-66.12). A 1-log increase in pfCHII was significantly associated with an increased hazard of death for the 1969 to 2017 seasons (HR, 2.02; 95% CI, 1.21-3.37; P = .01) after adjustment. The quadratic pfCHII was also statistically significant (HR, 0.91; 95% CI, 0.85-0.98; P = .01), indicating that the hazard of death increased at a decreasing rate, whereas the pfCHII increased.Conclusions and relevanceThe findings suggest that an increase in repetitive head impacts is associated with an increased hazard of death among NFL players. Reduction in repetitive head impacts from playing football or other activities through additional rule and equipment changes may be associated with reduced mortality.

Dataset Information

Neuroimaging of cognitive dysfunction and depression in aging retired National Football League players: a cross-sectional study.

Publications

Neuroimaging of cognitive dysfunction and depression in aging retired National Football League players: a cross-sectional study.

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