Association Between Antemortem FLAIR White Matter Hyperintensities and Neuropathology in Brain Donors Exposed to Repetitive Head Impacts

Uretsky, Madeline; Bouix, Sylvain; Killiany, Ronald; Tripodis, Yorghos; Martin, Brett; Palmisano, Joseph; Mian, Asim; Buch, Karen; Farris, Chad; Daneshvar, Daniel H.; Dwyer, Brigid; Goldstein, Lee E.; Katz, Douglas I.; Nowinski, Christopher J.; Cantu, Robert C.; Kowall, Neil W.; Huber, Bertrand R.; Stern, Robert; Alvarez, Victor E.; Stein, Thor D.; McKee, Ann C.; Mez, Jesse; Alosco, Michael L.

doi:10.1212/wnl.0000000000013012

Cited by 18 publications

(21 citation statements)

References 49 publications

(128 reference statements)

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“… In order to improve the stability of analysis, the Fourier series method should be used to reduce the interference of equipment, personnel, and other nonresistant factors. The calculation process is represented as

where P is the anti-interference ability in the process of data acquisition, t is the data acquisition time, y is the degree of data encryption, z is the transmission distance, and ξ is the interference coefficient [ 18 ]. …”

Section: Literature Reviewmentioning

confidence: 99%

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[Retracted] A Study on the Impact of Basketball on the Physical Fitness and Health of Adolescents Based on the Method of Correlation Analysis

Shao¹,

Yu-wei

2022

Journal of Environmental and Public Health

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Basketball can improve physical fitness, keep healthy, and become the main form of modern sports. However, basketball generally has the problem of unreasonable sports schemes and even reduces physical fitness. Therefore, finding an effective basketball program is an urgent problem to be solved at present. In order to improve the level of public health, this paper proposes a correlation analysis method to study the impact of basketball on teenagers’ health. The correlation analysis method is used to analyze the health data of adolescents, combined with the influence of basketball on fitness and the characteristics of basketball itself. Previous studies on basketball neglected comprehensive analysis and lack of correlation analysis of basketball indexes, resulting in unsatisfactory analysis results. The correlation analysis method can adjust the technical method, intensity, and program of basketball in combination with the physical development of teenagers. MATLAB simulation shows that the correlation analysis method can accurately analyze the impact of basketball on teenagers’ health, with an accuracy of 95%. Therefore, the correlation analysis method constructed in this paper can provide guidance for basketball and improve the health level of teenagers.

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Section: Literature Reviewmentioning

confidence: 99%

“…where P is the anti-interference ability in the process of data acquisition, t is the data acquisition time, y is the degree of data encryption, z is the transmission distance, and ξ is the interference coefficient [ 18 ].…”

Section: Literature Reviewmentioning

confidence: 99%

[Retracted] A Study on the Impact of Basketball on the Physical Fitness and Health of Adolescents Based on the Method of Correlation Analysis

Shao¹,

Yu-wei

2022

Journal of Environmental and Public Health

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“…This study contributes to the body of literature examining the chronic effects of high-contact sports, leveraging a multi-year study duration, advanced metrics, and tract-specificity. Future longitudinal studies that include more sports will complement our knowledge about brain changes due to head impacts in sports, while combined prospective imaging and histopathology studies in animals or even humans 63,64 might elucidate the pathological correlates of imaging changes.…”

Section: Discussionmentioning

confidence: 99%

Microstructural alterations in tract development in college football: a longitudinal diffusion MRI study

Goubran

Mills

Georgiadis

et al. 2022

Preprint

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Background and Objectives: Repeated concussive and sub-concussive impacts in high-contact sports can affect microstructure of the brain, which can be studied using diffusion MRI. Most prior imaging studies, however, employ a cross-sectional design, do not include low-contact players as controls, or use traditional diffusion tensor imaging without investigating novel tract-specific microstructural metrics. Methods: We examined brain microstructure in 63 high-contact (American football) and 34 low-contact (volleyball) collegiate athletes with up to 4 years of follow-up (315 total scans) using advanced diffusion MRI, a comprehensive set of multi-compartment models, and automated fiber quantification tools. We investigated diffusion metrics along the length of tracts using nested linear mixed-effects models to ascertain the acute and chronic effects of sub-concussive and concussive impacts, as well as associations between diffusion changes with clinical, behavioral, and sports-related measures. Results: Significant longitudinal increases in fractional anisotropy and axonal water fraction were detected in volleyball players, but not in football players, along with decreases in radial and mean diffusivity as well as orientation dispersion index (all findings absolute T-statistic > 3.5, p < .0001). This pattern was present in the callosum forceps minor, left superior longitudinal fasciculus, left thalamic radiation, and right cingulum hippocampus. Longitudinal group differences were more prominent and observed in a larger number of tracts in concussed (previously or in-study) football players (p < .0001), while smaller effects were noted in un-concussed players. An analysis of immediate-post concussion scans in football players demonstrated a transient localized increase in axial diffusivity, mean and radial kurtosis in the left uncinate and right cingulum hippocampus (p < .0001). Finally, football players with high position-based sub-concussive risk demonstrated increased orientation dispersion index over time (p < .0001). Discussion: The observed longitudinal changes in our volleyball cohort likely reflect normal development in this age range, while the relative attenuation of these effects seen in football, and especially concussed athletes, could possibly reveal diminished myelination, altered axonal calibers, or depressed pruning processes leading to a static, non-decreasing axonal dispersion. This prospective longitudinal study demonstrates significantly divergent tract-specific trajectories of brain microstructure, possibly reflecting a concussive and/or repeated sub-concussive impact-related alteration of normal white matter development in football athletes.

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“… 53 Additional research by our team that used samples of brain donors with autopsy-confirmed CTE directly linked greater years of American football play to more severe semi-quantitative ratings of white matter rarefaction 54 as well as to greater volumes of white matter hyperintensities on antemortem FLAIR magnetic resonance imaging. 55 These white matter pathologies correlated with informant-reported cognitive symptoms. 54 , 55 Similar to what is observed in the context of Alzheimer’s disease, 56 white matter pathologies likely contribute to cognitive, mood and/or behavioural symptoms in people exposed to RHI.…”

Section: Introductionmentioning

confidence: 96%

“… 55 These white matter pathologies correlated with informant-reported cognitive symptoms. 54 , 55 Similar to what is observed in the context of Alzheimer’s disease, 56 white matter pathologies likely contribute to cognitive, mood and/or behavioural symptoms in people exposed to RHI.…”

Section: Introductionmentioning

confidence: 96%

Decreased myelin proteins in brain donors exposed to football-related repetitive head impacts

Alosco

Mosaheb

et al. 2023

Brain Communications

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American football players and other individuals exposed to repetitive head impacts can exhibit a constellation of later-life cognitive and neuropsychiatric symptoms. While tau-based diseases such as chronic traumatic encephalopathy can underpin certain symptoms, contributions from non-tau pathologies from repetitive head impacts are increasingly recognized. We examined cross-sectional associations between myelin integrity using immunoassays for myelin-associated glycoprotein and proteolipid protein 1 with risk factors and clinical outcomes in brain donors exposed to repetitive head impacts from American football. Immunoassays for myelin-associated glycoprotein and proteolipid protein 1 were conducted on dorsolateral frontal white matter tissue samples of 205 male brain donors. Proxies of exposure to repetitive head impacts included years of exposure and age of first exposure to American football play. Informants completed the Functional Activities Questionnaire, Behavior Rating Inventory of Executive Function-Adult Version (Behavioral Regulation Index), and Barratt Impulsiveness Scale-11. Associations between myelin-associated glycoprotein and proteolipid protein 1 with exposure proxies and clinical scales were tested. Of the 205 male brain donors who played amateur and professional football, the mean age was 67.17 (SD = 16.78), and 75.9% (n = 126) were reported by informants to be functionally impaired prior to death. Myelin-associated glycoprotein and proteolipid protein 1 correlated with the ischaemic injury scale score, a global indicator of cerebrovascular disease (r = −0.23 and −0.20, respectively, Ps < 0.01). Chronic traumatic encephalopathy was the most common neurodegenerative disease (n = 151, 73.7%). Myelin-associated glycoprotein and proteolipid protein 1 were not associated with chronic traumatic encephalopathy status, but lower proteolipid protein 1 was associated with more severe chronic traumatic encephalopathy (P = 0.03). Myelin-associated glycoprotein and proteolipid protein 1 were not associated with other neurodegenerative disease pathologies. More years of football play was associated with lower proteolipid protein 1 [beta = −2.45, 95% confidence interval (CI) [−4.52, −0.38]] and compared with those who played <11 years of football (n = 78), those who played 11 or more years (n = 128) had lower myelin-associated glycoprotein (mean difference = 46.00, 95% CI [5.32, 86.69]) and proteolipid protein 1 (mean difference = 24.72, 95% CI [2.40, 47.05]). Younger age of first exposure corresponded to lower proteolipid protein 1 (beta = 4.35, 95% CI [0.25, 8.45]). Among brain donors who were aged 50 or older (n = 144), lower proteolipid protein 1 (beta = −0.02, 95% CI [−0.047, −0.001]) and myelin-associated glycoprotein (beta = −0.01, 95% CI [−0.03, −0.002]) were associated with higher Functional Activities Questionnaire scores. Lower myelin-associated glycoprotein correlated with higher Barratt Impulsiveness Scale-11 scores (beta = −0.02, 95% CI [−0.04, −0.0003]). Results suggest that decreased myelin may represent a late effect of repetitive head impacts that contributes to the manifestation of cognitive symptoms and impulsivity. Clinical–pathological correlation studies with prospective objective clinical assessments are needed to confirm our findings.

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Association Between Antemortem FLAIR White Matter Hyperintensities and Neuropathology in Brain Donors Exposed to Repetitive Head Impacts

Cited by 18 publications

References 49 publications

[Retracted] A Study on the Impact of Basketball on the Physical Fitness and Health of Adolescents Based on the Method of Correlation Analysis

[Retracted] A Study on the Impact of Basketball on the Physical Fitness and Health of Adolescents Based on the Method of Correlation Analysis

Microstructural alterations in tract development in college football: a longitudinal diffusion MRI study

Decreased myelin proteins in brain donors exposed to football-related repetitive head impacts

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