Lack of Influence of Apolipoprotein E Status on Cognition or Brain Structure in Professional Fighters

Banks, Sarah J.; Miller, Justin B.; Rissman, Robert A.; Bernick, Charles

doi:10.1089/neu.2016.4453

Cited by 14 publications

(12 citation statements)

References 12 publications

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“…Confounds that may affect an athlete’s CTE etiology include high body mass index and acquired systemic conditions (e.g., diabetes and hypertension) [89], which are general health factors associated with cognitive decline seen in non-CTE age-related dementias such as AD [82]. Although there is a higher incidence of neuropsychiatric disorders in athletes with CTE lesions [66, 96], similar behavioral conditions and brain pathology are seen in subjects without a diagnosis of CTE [8, 12, 37, 104, 108] making it difficult to discern the pathophysiological etiology of these ailments. This conundrum also applies to military veterans with post-traumatic stress disorder that present with neuropsychiatric conditions (e.g., depression) and brain structural abnormalities (e.g., decreased hippocampal volume) similar to CTE [34, 40, 91, 92, 102, 106].…”

Section: Discussionmentioning

confidence: 99%

Tau pathology in the medial temporal lobe of athletes with chronic traumatic encephalopathy: a chronic effects of neurotrauma consortium study

Kelley

Perez

Mufson

2019

acta neuropathol commun

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Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative condition associated with repetitive traumatic brain injury (rTBI) seen in contact-sport athletes and military personnel. The medial temporal lobe (MTL; i.e., hippocampus, subiculum, and entorhinal and perirhinal cortices) memory circuit displays tau lesions during the pathological progression of CTE. We examined MTL tissue obtained from 40 male Caucasian and African American athletes who received a postmortem CTE neuropathological diagnosis defined as stage II, III, or IV. Sections were immunolabeled using an early (AT8) or a late (TauC3) marker for pathological tau and for amyloid beta (Aβ) species (6E10, Aβ1–42 and thioflavin S). Stereological analysis revealed that stage III had significantly less AT8-positive neurons and dystrophic neurites than stage IV in all MTL regions except hippocampal subfield CA3, whereas significantly more AT8-positive neurons, dystrophic neurites, and neurite clusters were found in the perirhinal cortex, entorhinal cortex, hippocampal CA1, and subiculum of CTE stage III compared with stage II. TauC3-positive pathology was significantly higher in the perirhinal and subicular cortex of stage IV compared to stage III and the perirhinal cortex of stage III compared to stage II. AT8-positive neurite clusters were observed in stages III and IV, but virtually absent in stage II. When observed, Aβ pathology appeared as amyloid precursor protein (APP)/Aβ (6E10)-positive diffuse plaques independent of region. Thioflavine S labeling, did not reveal evidence for fibril or neuritic pathology associated with plaques, confirming a diffuse, non-cored plaque phenotype in CTE. Total number of AT8-positive profiles correlated with age at death, age at symptom onset, and time from retirement to death. There was no association between AT8-positive tau pathology and age sport began, years played, or retirement age, and no difference between CTE stage and the highest level of sport played. In summary, our findings demonstrate different tau profiles in the MTL across CTE stages, proffering CA3 tau pathology and MTL dystrophic neurite clusters as possible markers for the transition between early (II) and late (III/IV) stages, while highlighting CTE as a progressive noncommunicative tauopathy.

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Section: Discussionmentioning

confidence: 99%

Tau pathology in the medial temporal lobe of athletes with chronic traumatic encephalopathy: a chronic effects of neurotrauma consortium study

Kelley

Perez

Mufson

2019

acta neuropathol commun

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“…In fighters, thalamic volume decreased by 0.4% (right) and 0.3% (left) with each fight. 24 In a more recent study from the same group, Banks and colleagues 59 continued to find a statistically significant relationship between greater exposure and smaller thalamic volume. Moreover, apolipoprotein E genotype status did not impact this relationship.…”

Section: Thalamic Volume and Exposure To Rhimentioning

confidence: 93%

Age at First Exposure to Repetitive Head Impacts Is Associated with Smaller Thalamic Volumes in Former Professional American Football Players

Schultz

Stern

Tripodis

et al. 2018

Journal of Neurotrauma

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Thalamic atrophy has been associated with exposure to repetitive head impacts (RHI) in professional fighters. The aim of this study is to investigate whether or not age at first exposure (AFE) to RHI is associated with thalamic volume in symptomatic former National Football League (NFL) players at risk for chronic traumatic encephalopathy (CTE). Eighty-six symptomatic former NFL players (mean age = 54.9 ± 7.9 years) were included. T1-weighted data were acquired on a 3T magnetic resonance imager, and thalamic volumes were derived using FreeSurfer. Mood and behavior, psychomotor speed, and visual and verbal memory were assessed. The association between thalamic volume and AFE to playing football and to number of years playing was calculated. Decreased thalamic volume was associated with more years of play (left: p = 0.03; right: p = 0.03). Younger AFE was associated with decreased right thalamic volume (p = 0.014). This association remained significant after adjusting for total years of play. Decreased left thalamic volume was associated with worse visual memory (p = 0.014), whereas increased right thalamic volume was associated with fewer mood and behavior symptoms (p = 0.003). In our sample of symptomatic former NFL players at risk for CTE, total years of play and AFE were associated with decreased thalamic volume. The effect of AFE on right thalamic volume was almost twice as strong as the effect of total years of play. Our findings confirm previous reports of an association between thalamic volume and exposure to RHI. They suggest further that younger AFE may result in smaller thalamic volume later in life.

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“…The ε4 allele has also been linked to worse cognitive outcomes following TBI with some studies finding the allele associated with worse memory, processing speed, and overall increased cognitive impairment (144)(145)(146). However, not all studies have found an association with worse cognitive outcome and so further work is needed (147)(148)(149). Currently, the association of the APOE ε4 allele with poor outcomes is thought to be mediated by abnormal lysing of its protein product resulting in neurotoxic byproducts that worsen secondary injury and impair recovery (28).…”

Section: Candidate Gene Studies and Genome-wide Association Workmentioning

confidence: 99%

Integrative Neuroinformatics for Precision Prognostication and Personalized Therapeutics in Moderate and Severe Traumatic Brain Injury

et al. 2021

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Despite changes in guideline-based management of moderate/severe traumatic brain injury (TBI) over the preceding decades, little impact on mortality and morbidity have been seen. This argues against the “one-treatment fits all” approach to such management strategies. With this, some preliminary advances in the area of personalized medicine in TBI care have displayed promising results. However, to continue transitioning toward individually-tailored care, we require integration of complex “-omics” data sets. The past few decades have seen dramatic increases in the volume of complex multi-modal data in moderate and severe TBI care. Such data includes serial high-fidelity multi-modal characterization of the cerebral physiome, serum/cerebrospinal fluid proteomics, admission genetic profiles, and serial advanced neuroimaging modalities. Integrating these complex and serially obtained data sets, with patient baseline demographics, treatment information and clinical outcomes over time, can be a daunting task for the treating clinician. Within this review, we highlight the current status of such multi-modal omics data sets in moderate/severe TBI, current limitations to the utilization of such data, and a potential path forward through employing integrative neuroinformatic approaches, which are applied in other neuropathologies. Such advances are positioned to facilitate the transition to precision prognostication and inform a top-down approach to the development of personalized therapeutics in moderate/severe TBI.

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Lack of Influence of Apolipoprotein E Status on Cognition or Brain Structure in Professional Fighters

Cited by 14 publications

References 12 publications

Tau pathology in the medial temporal lobe of athletes with chronic traumatic encephalopathy: a chronic effects of neurotrauma consortium study

Tau pathology in the medial temporal lobe of athletes with chronic traumatic encephalopathy: a chronic effects of neurotrauma consortium study

Age at First Exposure to Repetitive Head Impacts Is Associated with Smaller Thalamic Volumes in Former Professional American Football Players

Integrative Neuroinformatics for Precision Prognostication and Personalized Therapeutics in Moderate and Severe Traumatic Brain Injury

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