Associations of Apolipoprotein E ε4 Genotype and Ball Heading With Verbal Memory in Amateur Soccer Players

Hunter, Liane E.; Freudenberg-Hua, Yun; Davies, Peter; Kim, Mimi; Lipton, Richard B.; Stewart, Walter F.; Srinivasan, Priyanka; Hu, Shiping; Lipton, Michael L.

doi:10.1001/jamaneurol.2019.4828

Cited by 20 publications

(21 citation statements)

References 33 publications

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“…Our findings concur with previous studies highlighting impaired cognition in male football players 18,19 . Importantly, our study extends these findings providing mechanistic insight into the underlying mechanisms that may predispose to an accelerated trajectory toward neurodegeneration 2 5 and neurogenerative 6 disease.…”

Section: Discussionsupporting

confidence: 92%

“…Football players are at increased risk of neurodegeneration including dementia in later life, 1 the likely consequence of repetitive mechanical trauma caused by heading the ball 2 . While research has traditionally focused on structural abnormalities, 3 there has been less attention focused on potential impairments in cerebral blood flow (CBF) regulation to which cerebrovascular reactivity to carbon dioxide (CVR CO2 ) is a primary determinant.…”

Section: Introductionmentioning

confidence: 99%

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Impaired cerebral blood flow regulation and cognition in male football players

Marley

Owens

Tsukamoto

et al. 2021

Scandinavian Med Sci Sports

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Football players are at increased risk of neurodegeneration, the likely consequence of repetitive mechanical trauma caused by heading the ball. However, to what extent a history of heading the ball affects cerebral blood flow (CBF) regulation and its potential relationship to cognitive impairment is unknown. To address this, we recruited 16 concussion‐free male amateur football players (age: 25 ± 6 y) with a history of heading the ball (18 ± 6 y) and 18 sex, age, education, and activity‐matched controls with no prior history of contact sport participation or concussion. Cerebral perfusion was measured at rest and in response to both hyper/hypocapnia to determine cerebrovascular reactivity to carbon dioxide (CVRCO2HYPER/HYPO) using transcranial Doppler ultrasound and capnography, with the sum reflecting the cerebral vasomotor range. Cognition and visuomotor coordination were assessed using the Montreal cognitive assessment (MoCA) and the Grooved Pegboard Dexterity Test (GPD), respectively. While no differences in cerebral perfusion were observed (p = 0.938), CVRCO2HYPER/HYPO (p = 0.038/p = 0.025), cerebral vasomotor range (p = 0.002), MoCA (p = 0.027), and GPD performance (dominant hand, P ≤ 0.001) were consistently lower in the players compared to controls. These findings are the first to demonstrate that CBF regulation and cognition are collectively impaired in male football players with history of heading the ball, which may contribute to neurodegeneration.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Impaired cerebral blood flow regulation and cognition in male football players

Marley

Owens

Tsukamoto

et al. 2021

Scandinavian Med Sci Sports

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“…The trajectory results show that the maximal decliner group is associated with both being female and worse outcomes, which may seem counterintuitive. These findings may perhaps be a function of the presence of APOE ε4 allele, given its interaction with tau pathogenesis and association with outcome after SRC (11,36,37). Future work should evaluate the genetic drivers of biomarker profile and cognitive impairment after SRC in a sex-specific manner to identify novel pathways of risk and promote safer sports play.…”

Section: Discussionmentioning

confidence: 99%

Sex Differences in Circulating T-Tau Trajectories After Sports-Concussion and Correlation With Outcome

et al. 2020

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Sex differences in molecular biomarkers after sports-related concussion (SRC) could steadily advance our understanding of injury heterogeneity and complexity, and help capture phenotypic characteristics, by unveiling sex-dependent pathobiological processes and disease mechanisms. Such knowledge will help improve diagnosis, clinical management, and prognosis. Total-tau (t-tau) has recently emerged as a promising blood marker showing sex-associated differences in neurodegenerative diseases. Nonetheless, to date, little is known about the potential influence of sex on its injury-related concentration and dynamics after SRC. We hypothesized that measurements of circulating levels of t-tau over time would reflect a differential vulnerability signature, providing insights into the sex-related phenotypes and their relationship with clinical outcomes. To test this hypothesis, plasma levels of t-tau were measured using an ultrasensitive immunoassay up to 7 days after injury, in 46 concussed athletes (20 males, 26 females). We used trajectory analysis to generate two distinct temporal profiles of t-tau, which were then compared with gender and return to play (RTP). The majority of subjects (∼63%) started with low t-tau concentrations that further declined within the first 48 h; while the remaining ("maximal decliners") started with concentrations comparable to the baseline levels that also fell over time, but persisting markedly higher compared with the first profile. The maximal decliner group was primarily composed of female subjects (p = 0.007) and was significantly associated with poor outcome (RTP ≥ 10 days after concussion) (p = 0.011). Taken together, our data provide evidence for the existence of sex-related biosignatures following sports-related concussions, possibly indicating a differential effect as a result of distinct brain vulnerability and inherent injury response. Future studies will be required to further elucidate underlying sex-based biological and pathophysiological mechanisms, and determine the value of t-tau signatures for management and therapeutic decision-making in sports-related concussions.

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“…Furthermore, the use of caregivers as controls could have led to some mitigation of the real association between environmental risk factors and disease risk in our study, because most of the caregivers were family members and may have shared lifestyle habits with EOD cases, thus reducing the strength of the associations we estimated. Finally, we have no availability of genetic status for the referent population, thus precluding the possibility of assessing their role in disease risk [71,72].…”

Section: Discussionmentioning

confidence: 99%

Environmental Risk Factors for Early-Onset Alzheimer’s Dementia and Frontotemporal Dementia: A Case-Control Study in Northern Italy

Adani

Filippini

Garuti

et al. 2020

IJERPH

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Background: Early-onset dementia (EOD) is defined as dementia with symptom onset before 65 years. The role of environmental risk factors in the etiology of EOD is still undefined. We aimed at assessing the role of environmental risk factors in EOD etiology, taking into account its different clinical types. Methods: Using a case-control study, we recruited all EOD cases referred to Modena hospitals from 2016 to 2019, while the referent population was drawn from cases’ caregivers. We investigated residential history, occupational and environmental exposures to chemicals and lifestyle behaviors through a self-administered questionnaire. We computed the odds ratios of EOD risk (overall and restricting to the Alzheimer’s dementia (AD) or frontotemporal dementia (FTD) diagnoses) and the corresponding 95% confidence intervals using an unconditional logistic regression model. Results: Fifty-eight EOD patients (19 FTD and 32 AD) and 54 controls agreed to participate. Most of the investigated exposures, such as occupational exposure to aluminum, pesticides, dyes, paints or thinners, were associated with an increased odds ratio (OR) for FTD but not for AD. Long-term use of selenium-containing dietary supplements was associated with increased OR for EOD and, particularly, for FTD. For both EOD forms, smoking and playing football showed an increased odds ratio, while cycling was associated with increased risk only in FTD. Overall sports practice appeared to be a protective factor for both types. Conclusions: Our results suggest a role of environmental and behavioral risk factors such as some chemical exposures and professional sports in EOD etiology, in particular with reference to FTD. Overall sports practice may be associated with a reduced EOD risk.

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Associations of Apolipoprotein E ε4 Genotype and Ball Heading With Verbal Memory in Amateur Soccer Players

Cited by 20 publications

References 33 publications

Impaired cerebral blood flow regulation and cognition in male football players

Impaired cerebral blood flow regulation and cognition in male football players

Sex Differences in Circulating T-Tau Trajectories After Sports-Concussion and Correlation With Outcome

Environmental Risk Factors for Early-Onset Alzheimer’s Dementia and Frontotemporal Dementia: A Case-Control Study in Northern Italy

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