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Cumulative Head Impact Exposure Predicts Later-Life Depression, Apathy, Executive Dysfunction, and Cognitive Impairment in Former High School and College Football Players.

ABSTRACT: The term "repetitive head impacts" (RHI) refers to the cumulative exposure to concussive and subconcussive events. Although RHI are believed to increase risk for later-life neurological consequences (including chronic traumatic encephalopathy), quantitative analysis of this relationship has not yet been examined because of the lack of validated tools to quantify lifetime RHI exposure. The objectives of this study were: 1) to develop a metric to quantify cumulative RHI exposure from football, which we term the "cumulative head impact index" (CHII); 2) to use the CHII to examine the association between RHI exposure and long-term clinical outcomes; and 3) to evaluate its predictive properties relative to other exposure metrics (i.e., duration of play, age of first exposure, concussion history). Participants included 93 former high school and collegiate football players who completed objective cognitive and self-reported behavioral/mood tests as part of a larger ongoing longitudinal study. Using established cutoff scores, we transformed continuous outcomes into dichotomous variables (normal vs. impaired). The CHII was computed for each participant and derived from a combination of self-reported athletic history (i.e., number of seasons, position[s], levels played), and impact frequencies reported in helmet accelerometer studies. A bivariate probit, instrumental variable model revealed a threshold dose-response relationship between the CHII and risk for later-life cognitive impairment (p?

SUBMITTER: Montenigro PH

PROVIDER: S-EPMC5220530 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Cumulative Head Impact Exposure Predicts Later-Life Depression, Apathy, Executive Dysfunction, and Cognitive Impairment in Former High School and College Football Players.

Montenigro Philip H PH Alosco Michael L ML Martin Brett M BM Daneshvar Daniel H DH Mez Jesse J Chaisson Christine E CE Nowinski Christopher J CJ Au Rhoda R McKee Ann C AC Cantu Robert C RC McClean Michael D MD Stern Robert A RA Tripodis Yorghos Y

Journal of neurotrauma 20160615 2

The term "repetitive head impacts" (RHI) refers to the cumulative exposure to concussive and subconcussive events. Although RHI are believed to increase risk for later-life neurological consequences (including chronic traumatic encephalopathy), quantitative analysis of this relationship has not yet been examined because of the lack of validated tools to quantify lifetime RHI exposure. The objectives of this study were: 1) to develop a metric to quantify cumulative RHI exposure from football, whi ...[more]

PMID: 27029716

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Project description:ImportancePilot studies that involved early imaging of the 18 kDa translocator protein (TSPO) using positron emission tomography (PET) indicated high levels of TSPO in the brains of active or former National Football League (NFL) players. If validated further in larger studies, those findings may have implications for athletes involved in collision sport.ObjectiveTo test for higher TSPO that marks brain injury and repair in a relatively large, unique cohort of former NFL players compared with former elite, noncollision sport athletes.Design, setting, and participantsThis cross-sectional study used carbon 11-labeled N,N-diethyl-2-(4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide positron emission tomography ([11C]DPA-713 PET) data from former NFL players within 12 years of last participation in the NFL and elite noncollision sport athletes from across the US. Participants were enrolled between April 2018 and February 2023.Main outcomes and measuresRegional [11C]DPA-713 total distribution volume from [11C]DPA-713 PET that is a measure of regional brain TSPO; regional brain volumes on magnetic resonance imaging; neuropsychological performance, including attention, executive function, and memory domains.ResultsThis study included 27 former NFL players and 27 former elite, noncollision sport athletes. Regional TSPO levels were higher in former NFL players compared with former elite, noncollision sport athletes (unstandardized β coefficient, 1.08; SE, 0.22; 95% CI, 0.65 to 1.52; P < .001). The magnitude of the group difference depended on region, with largest group differences in TSPO in cingulate and frontal cortices as well as hippocampus. Compared with noncollision sport athletes, former NFL players performed worse in learning (mean difference [MD], -0.70; 95% CI, -1.14 to -0.25; P = .003) and memory (MD, -0.77; 95% CI, -1.24 to -0.30; P = .002), with no correlation between total gray matter TSPO and these cognitive domains.Conclusions and relevanceIn this cross-sectional study using [11C]DPA-713 PET, higher brain TSPO was found in former NFL players compared with noncollision sport athletes. This finding is consistent with neuroimmune activation even after cessation of NFL play. Future longitudinal [11C]DPA-713 PET and neuropsychological testing promises to inform whether neuroimmune-modulating therapy may be warranted.

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:ImportanceRepetitive subconcussive head impacts in sports have emerged as a complex public health issue. Most of these head impacts remain asymptomatic yet have the potential to cause insidious neurological deficit if sustained repetitively. Near point of convergence (NPC) values have shown to reflect subclinical neuronal damage; however, the longitudinal pattern of NPC changes in association with subconcussive head impacts remains unclear.ObjectivesTo examine the NPC response to recurring subconcussive head impacts in a single high school football season through a series of repeated measurements.Design, setting, and participantsThis prospective case-series study of US varsity high school football players included baseline measurements of NPC, measurements at pregame and postgame points from 6 in-season games, and postseason follow-up measurements (a total of 14 points). An accelerometer-embedded mouthguard measured head impact frequency and magnitude from all practices and games. During the 6 games, players wore chest-strap heart rate monitors to record heart rate and estimate their excess postexercise oxygen consumption, accounting for possible physical exertion effects on NPC values.ExposuresPlayers participated in practices and games with no restriction.Main outcomes and measuresNear point of convergence.ResultsThe 12 included players were all boys, with a mean (SD) age of 16.4 (0.5) years. A total of 8009 head impacts, 177 907 g of peak linear acceleration, and 16 123 371 rad/s2 of peak rotational acceleration were recorded from the players in a single football season. There was a significant increase in NPC over time until the middle of the season (mean [SD] NPC: baseline, 5.25 [1.49] cm; pregame 3, 6.42 [1.93] cm; P = .01), which was significantly associated with subconcussive head impact frequency and magnitude (0.02 cm per 100 g of peak linear acceleration [SE, 0.0108; 95% CI, 0.0436-0.004]; P = .01; 0.023 cm per 10 000 rad/s2 of peak rotational acceleration [SE, 0.009; 95% CI, 0.041-0.0105]; P = .02). However, NPC values began to normalize toward baseline level from midseason (mean [SD] NPC: baseline, 5.25 [1.49] cm; pregame 6, 5.75 [2.23] cm; P = .32), as supported by a significant quadratic trend (β [SE], -0.002 [0.001] cm/d; P = .003), while participants continued to incur subconcussive head impacts.Conclusions and relevanceThis longitudinal case series study suggests that NPC can be perturbed over the long term by subconcussive head impacts but may normalize over time. The oculomotor system may have an adaptational capacity to subclinical head impacts, yet the mechanism for such remains an open question and warrants further investigation.

Dataset Information

Cumulative Head Impact Exposure Predicts Later-Life Depression, Apathy, Executive Dysfunction, and Cognitive Impairment in Former High School and College Football Players.

Publications

Cumulative Head Impact Exposure Predicts Later-Life Depression, Apathy, Executive Dysfunction, and Cognitive Impairment in Former High School and College Football Players.

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