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  1. Article ; Online: New Insights Into the APOE ε4-Soccer Heading Interaction: Handle With Care.

    Banks, Sarah J / Mez, Jesse

    JAMA neurology

    2020  Volume 77, Issue 4, Page(s) 417–418

    MeSH term(s) Apolipoprotein E4/genetics ; Athletes ; Brain Concussion ; Genotype ; Humans ; Soccer
    Chemical Substances Apolipoprotein E4
    Language English
    Publishing date 2020-01-23
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 2702023-X
    ISSN 2168-6157 ; 2168-6149
    ISSN (online) 2168-6157
    ISSN 2168-6149
    DOI 10.1001/jamaneurol.2019.4451
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Chronic traumatic encephalopathy and aging-related tau astrogliopathy in community-dwelling older persons with and without moderate-to-severe traumatic brain injury.

    Agrawal, Sonal / Leurgans, Sue E / Barnes, Lisa L / Dams-O'Connor, Kristen / Mez, Jesse / Bennett, David A / Schneider, Julie A

    Journal of neuropathology and experimental neurology

    2024  Volume 83, Issue 3, Page(s) 181–193

    Abstract: This study examined the frequency of chronic traumatic encephalopathy-neuropathologic change (CTE-NC) and aging-related tau astrogliopathy (ARTAG) in community-dwelling older adults and tested the hypothesis that these tau pathologies are associated with ...

    Abstract This study examined the frequency of chronic traumatic encephalopathy-neuropathologic change (CTE-NC) and aging-related tau astrogliopathy (ARTAG) in community-dwelling older adults and tested the hypothesis that these tau pathologies are associated with a history of moderate-to-severe traumatic brain injury (msTBI), defined as a TBI with loss of consciousness >30 minutes. We evaluated CTE-NC, ARTAG, and Alzheimer disease pathologies in 94 participants with msTBI and 94 participants without TBI matched by age, sex, education, and dementia status TBI from the Rush community-based cohorts. Six (3%) of brains showed the pathognomonic lesion of CTE-NC; only 3 of these had a history of msTBI. In contrast, ARTAG was common in older brains (gray matter ARTAG = 77%; white matter ARTAG = 54%; subpial ARTAG = 51%); there were no differences in severity, type, or distribution of ARTAG pathology with respect to history of msTBI. Furthermore, those with msTBI did not have higher levels of PHF-tau tangles density but had higher levels of amyloid-β load (Estimate = 0.339, SE = 0.164, p = 0.040). These findings suggest that CTE-NC is infrequent while ARTAG is common in the community and that both pathologies are unrelated to msTBI. The association of msTBI with amyloid-β, rather than with tauopathies suggests differential mechanisms of neurodegeneration in msTBI.
    MeSH term(s) Humans ; Aged ; Aged, 80 and over ; Chronic Traumatic Encephalopathy/pathology ; Independent Living ; Astrocytes/pathology ; tau Proteins/metabolism ; Aging/pathology ; Brain/pathology ; Brain Injuries, Traumatic/complications ; Brain Injuries, Traumatic/pathology ; Alzheimer Disease/pathology ; Amyloid beta-Peptides
    Chemical Substances tau Proteins ; Amyloid beta-Peptides
    Language English
    Publishing date 2024-02-01
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 3088-0
    ISSN 1554-6578 ; 0022-3069
    ISSN (online) 1554-6578
    ISSN 0022-3069
    DOI 10.1093/jnen/nlae007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Neuroimaging Biomarkers of Chronic Traumatic Encephalopathy: Targets for the Academic Memory Disorders Clinic.

    Alosco, Michael L / Culhane, Julia / Mez, Jesse

    Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics

    2021  Volume 18, Issue 2, Page(s) 772–791

    Abstract: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts, such as those from contact sports. The pathognomonic lesion for CTE is the perivascular accumulation of hyper-phosphorylated tau in ...

    Abstract Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts, such as those from contact sports. The pathognomonic lesion for CTE is the perivascular accumulation of hyper-phosphorylated tau in neurons and other cell process at the depths of sulci. CTE cannot be diagnosed during life at this time, limiting research on risk factors, mechanisms, epidemiology, and treatment. There is an urgent need for in vivo biomarkers that can accurately detect CTE and differentiate it from other neurological disorders. Neuroimaging is an integral component of the clinical evaluation of neurodegenerative diseases and will likely aid in diagnosing CTE during life. In this qualitative review, we present the current evidence on neuroimaging biomarkers for CTE with a focus on molecular, structural, and functional modalities routinely used as part of a dementia evaluation. Supporting imaging-pathological correlation studies are also presented. We targeted neuroimaging studies of living participants at high risk for CTE (e.g., aging former elite American football players, fighters). We conclude that an optimal tau PET radiotracer with high affinity for the 3R/4R neurofibrillary tangles in CTE has not yet been identified. Amyloid PET scans have tended to be negative. Converging structural and functional imaging evidence together with neuropathological evidence show frontotemporal and medial temporal lobe neurodegeneration, and increased likelihood for a cavum septum pellucidum. The literature offers promising neuroimaging biomarker targets of CTE, but it is limited by cross-sectional studies of small samples where the presence of underlying CTE is unknown. Imaging-pathological correlation studies will be important for the development and validation of neuroimaging biomarkers of CTE.
    MeSH term(s) Academic Medical Centers/trends ; Biomarkers/metabolism ; Chronic Traumatic Encephalopathy/diagnostic imaging ; Chronic Traumatic Encephalopathy/metabolism ; Chronic Traumatic Encephalopathy/therapy ; Humans ; Magnetic Resonance Imaging/methods ; Magnetic Resonance Imaging/trends ; Memory Disorders/diagnostic imaging ; Memory Disorders/metabolism ; Memory Disorders/therapy ; Neuroimaging/methods ; Neuroimaging/trends ; Positron-Emission Tomography/methods ; Positron-Emission Tomography/trends ; tau Proteins/metabolism
    Chemical Substances Biomarkers ; MAPT protein, human ; tau Proteins
    Language English
    Publishing date 2021-04-13
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 2316693-9
    ISSN 1878-7479 ; 1933-7213
    ISSN (online) 1878-7479
    ISSN 1933-7213
    DOI 10.1007/s13311-021-01028-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Chronic Traumatic Encephalopathy.

    Mez, Jesse / Stern, Robert A / McKee, Ann C

    Seminars in neurology

    2020  Volume 40, Issue 4, Page(s) 351–352

    MeSH term(s) Chronic Traumatic Encephalopathy/diagnosis ; Chronic Traumatic Encephalopathy/etiology ; Chronic Traumatic Encephalopathy/history ; History, 20th Century ; History, 21st Century ; Humans
    Language English
    Publishing date 2020-09-09
    Publishing country United States
    Document type Editorial ; Historical Article ; Introductory Journal Article
    ZDB-ID 603165-1
    ISSN 1098-9021 ; 0271-8235
    ISSN (online) 1098-9021
    ISSN 0271-8235
    DOI 10.1055/s-0040-1715824
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Genetics of Chronic Traumatic Encephalopathy.

    Abdolmohammadi, Bobak / Dupre, Alicia / Evers, Laney / Mez, Jesse

    Seminars in neurology

    2020  Volume 40, Issue 4, Page(s) 420–429

    Abstract: Although chronic traumatic encephalopathy (CTE) garners substantial attention in the media and there have been marked scientific advances in the last few years, much remains unclear about the role of genetic risk in CTE. Two athletes with comparable ... ...

    Abstract Although chronic traumatic encephalopathy (CTE) garners substantial attention in the media and there have been marked scientific advances in the last few years, much remains unclear about the role of genetic risk in CTE. Two athletes with comparable contact-sport exposure may have varying amounts of CTE neuropathology, suggesting that other factors, including genetics, may contribute to CTE risk and severity. In this review, we explore reasons why genetics may be important for CTE, concepts in genetic study design for CTE (including choosing controls, endophenotypes, gene by environment interaction, and epigenetics), implicated genes in CTE (including
    MeSH term(s) Apolipoproteins E/genetics ; Chronic Traumatic Encephalopathy/diagnosis ; Chronic Traumatic Encephalopathy/genetics ; Humans ; Membrane Proteins/genetics ; Nerve Tissue Proteins/genetics ; tau Proteins/genetics
    Chemical Substances ApoE protein, human ; Apolipoproteins E ; MAPT protein, human ; Membrane Proteins ; Nerve Tissue Proteins ; TMEM106B protein, human ; tau Proteins
    Language English
    Publishing date 2020-07-26
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 603165-1
    ISSN 1098-9021 ; 0271-8235
    ISSN (online) 1098-9021
    ISSN 0271-8235
    DOI 10.1055/s-0040-1713631
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Inflammation and neuronal gene expression changes differ in early versus late chronic traumatic encephalopathy brain.

    Labadorf, Adam / Agus, Filisia / Aytan, Nurgul / Cherry, Jonathan / Mez, Jesse / McKee, Ann / Stein, Thor D

    BMC medical genomics

    2023  Volume 16, Issue 1, Page(s) 49

    Abstract: Background: Our understanding of the molecular underpinnings of chronic traumatic encephalopathy (CTE) and its associated pathology in post-mortem brain is incomplete. Factors including years of play and genetic risk variants influence the extent of tau ...

    Abstract Background: Our understanding of the molecular underpinnings of chronic traumatic encephalopathy (CTE) and its associated pathology in post-mortem brain is incomplete. Factors including years of play and genetic risk variants influence the extent of tau pathology associated with disease expression, but how these factors affect gene expression, and whether those effects are consistent across the development of disease, is unknown.
    Methods: To address these questions, we conducted an analysis of the largest post-mortem brain CTE mRNASeq whole-transcriptome dataset available to date. We examined the genes and biological processes associated with disease by comparing individuals with CTE with control individuals with a history of repetitive head impacts that lack CTE pathology. We then identified genes and biological processes associated with total years of play as a measure of exposure, amount of tau pathology present at time of death, and the presence of APOE and TMEM106B risk variants. Samples were stratified into low and high pathology groups based on McKee CTE staging criteria to model early versus late changes in response to exposure, and the relative effects associated with these factors were compared between these groups.
    Results: Substantial gene expression changes were associated with severe disease for most of these factors, primarily implicating diverse, strongly involved neuroinflammatory and neuroimmune processes. In contrast, low pathology groups had many fewer genes and processes implicated and show striking differences for some factors when compared with severe disease. Specifically, gene expression associated with amount of tau pathology showed a nearly perfect inverse relationship when compared between these two groups.
    Conclusions: Together, these results suggest the early CTE disease process may be mechanistically different than what occurs in late stages, that total years of play and tau pathology influence disease expression differently, and that related pathology-modifying risk variants may do so via distinct biological pathways.
    MeSH term(s) Humans ; Chronic Traumatic Encephalopathy/genetics ; Chronic Traumatic Encephalopathy/metabolism ; Chronic Traumatic Encephalopathy/pathology ; tau Proteins/genetics ; tau Proteins/metabolism ; Brain/metabolism ; Inflammation/metabolism ; Transcriptome ; Membrane Proteins/genetics ; Nerve Tissue Proteins/genetics
    Chemical Substances tau Proteins ; TMEM106B protein, human ; Membrane Proteins ; Nerve Tissue Proteins
    Language English
    Publishing date 2023-03-09
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2411865-5
    ISSN 1755-8794 ; 1755-8794
    ISSN (online) 1755-8794
    ISSN 1755-8794
    DOI 10.1186/s12920-023-01471-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Clinical Presentation of Chronic Traumatic Encephalopathy.

    Mariani, Megan / Alosco, Michael L / Mez, Jesse / Stern, Robert A

    Seminars in neurology

    2020  Volume 40, Issue 4, Page(s) 370–383

    Abstract: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive head impacts (RHI), such as those received in contact/collision sports, blast injury in military veterans, and domestic violence. Currently, CTE can only be ... ...

    Abstract Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive head impacts (RHI), such as those received in contact/collision sports, blast injury in military veterans, and domestic violence. Currently, CTE can only be diagnosed following death. Although the clinical features of former boxers have been described for almost a century, and there is increasing evidence of long-term cognitive and neuropsychiatric impairments in living former American football players, the specific clinical presentation associated with underlying CTE neuropathology remains unclear. These features include diverse and nonspecific changes in cognition, mood, behavior, and motor functioning. Currently, there are no validated and widely accepted clinical diagnostic criteria. Proposed criteria are primarily based on retrospective telephonic interviews with the next of kin of individuals who were diagnosed with CTE postmortem. Prospective studies involving individuals presumably at high risk for CTE are underway; these will hopefully clarify the clinical features and course of CTE, allow the diagnostic criteria to be refined, and lead to the development and validation of in vivo biomarkers. This article reviews what is currently known about the clinical presentation of CTE and describes the evolution of this knowledge from early case reports of "punch drunk" boxers through larger case series of neuropathologically confirmed CTE. This article concludes with a discussion of gaps in research and future directions to address these areas.
    MeSH term(s) Athletic Injuries/complications ; Athletic Injuries/diagnosis ; Athletic Injuries/physiopathology ; Behavioral Symptoms/diagnosis ; Behavioral Symptoms/etiology ; Behavioral Symptoms/physiopathology ; Chronic Traumatic Encephalopathy/complications ; Chronic Traumatic Encephalopathy/diagnosis ; Chronic Traumatic Encephalopathy/physiopathology ; Cognitive Dysfunction/diagnosis ; Cognitive Dysfunction/etiology ; Cognitive Dysfunction/physiopathology ; Humans
    Language English
    Publishing date 2020-08-02
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 603165-1
    ISSN 1098-9021 ; 0271-8235
    ISSN (online) 1098-9021
    ISSN 0271-8235
    DOI 10.1055/s-0040-1713624
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Risk Factors for Chronic Traumatic Encephalopathy: A Proposed Framework.

    Phelps, Alyssa / Mez, Jesse / Stern, Robert A / Alosco, Michael L

    Seminars in neurology

    2020  Volume 40, Issue 4, Page(s) 439–449

    Abstract: Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that has been neuropathologically diagnosed in contact and collision sport athletes, military veterans, and others with a history of exposure to repetitive head impacts ( ... ...

    Abstract Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that has been neuropathologically diagnosed in contact and collision sport athletes, military veterans, and others with a history of exposure to repetitive head impacts (RHI). Identifying methods to diagnose and prevent CTE during life is a high priority. Timely diagnosis and implementation of treatment and preventative strategies for neurodegenerative diseases, including CTE, partially hinge upon early and accurate risk characterization. Here, we propose a framework of risk factors that influence the neuropathological development of CTE. We provide an up-to-date review of the literature examining cumulative exposure to RHI as the environmental trigger for CTE. Because not all individuals exposed to RHI develop CTE, the direct and/or indirect influence of nonhead trauma exposure characteristics (e.g., age, sex, race, genetics) on the pathological development of CTE is reviewed. We conclude with recommendations for future directions, as well as opinions for preventative strategies that could mitigate risk.
    MeSH term(s) Brain Concussion/complications ; Chronic Traumatic Encephalopathy/etiology ; Humans ; Risk Factors
    Language English
    Publishing date 2020-07-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 603165-1
    ISSN 1098-9021 ; 0271-8235
    ISSN (online) 1098-9021
    ISSN 0271-8235
    DOI 10.1055/s-0040-1713633
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Reader Response: Association of Position Played and Career Duration and Chronic Traumatic Encephalopathy at Autopsy in Elite Football and Hockey Players.

    Mez, Jesse / Alosco, Michael L / Nowinski, Christopher J / McKee, Ann C / Tripodis, Yorghos

    Neurology

    2021  Volume 97, Issue 6, Page(s) 297–298

    MeSH term(s) Athletes ; Autopsy ; Chronic Traumatic Encephalopathy ; Football ; Hockey ; Humans ; Soccer
    Language English
    Publishing date 2021-08-10
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 207147-2
    ISSN 1526-632X ; 0028-3878
    ISSN (online) 1526-632X
    ISSN 0028-3878
    DOI 10.1212/WNL.0000000000012381
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Association of Playing College American Football With Long-term Health Outcomes and Mortality.

    Phelps, Alyssa / Alosco, Michael L / Baucom, Zachary / Hartlage, Kaitlin / Palmisano, Joseph N / Weuve, Jennifer / Mez, Jesse / Tripodis, Yorghos / Stern, Robert A

    JAMA network open

    2022  Volume 5, Issue 4, Page(s) e228775

    Abstract: Importance: Exposure to repetitive head impacts from playing American football (including impacts resulting in symptomatic concussions and subconcussive trauma) is associated with increased risk for later-life health problems, including cognitive and ... ...

    Abstract Importance: Exposure to repetitive head impacts from playing American football (including impacts resulting in symptomatic concussions and subconcussive trauma) is associated with increased risk for later-life health problems, including cognitive and neuropsychiatric decline and neurodegenerative disease. Most research on long-term health consequences of playing football has focused on former professional athletes, with limited studies of former college players.
    Objectives: To estimate the prevalence of self-reported health conditions among former college football players compared with a sample of men in the general population as well as standardized mortality ratios (SMRs) among former college football players.
    Design, setting, and participants: This cohort study included data from 447 former University of Notre Dame (ND) football players aged 59 to 75 years who were seniors on the rosters from 1964 to 1980. A health outcomes survey was distributed to living players and next of kin of deceased players for whom contact information was available. The survey was completed from December 2018 to May 2019.
    Exposure: Participation in football at ND.
    Main outcomes and measures: Prevalence of health outcomes was compared between living former players who completed the survey and propensity score-matched participants in the Health and Retirement Study (HRS). Standardized mortality ratios of all causes and specific causes of death among all former players were compared with those among men in the general US population.
    Results: A total of 216 living players completed the health survey (median age, 67 years; IQR, 63-70 years) and were compared with 638 participants in the HRS (median age, 66 years; IQR, 63-70 years). Former players reported a higher prevalence of cognitive impairment (10 [5%] vs 8 [1%]; P = .02), headaches (22 [10%] vs 22 [4%]; P = .001), cardiovascular disease (70 [33%] vs 128 [20%]; P = .001), hypercholesterolemia (111 [52%] vs 182 [29%]; P = .001), and alcohol use (185 [86%] vs 489 [77%]; P = .02) and a lower prevalence of diabetes (24 [11%] vs 146 [23%]; P = .001). All-cause mortality (SMR, 0.54; 95% CI, 0.42-0.67) and mortality from heart (SMR, 0.64; 95% CI, 0.39-0.99), circulatory (SMR, 0.23; 95% CI, 0.03-0.83), respiratory (SMR, 0.13; 95% CI, 0.00-0.70), and digestive system (SMR, 0.13; 95% CI, 0.00-0.74) disorders; lung cancer (SMR, 0.26; 95% CI, 0.05-0.77); and violence (SMR, 0.10; 95% CI, 0.00-0.58) were significantly lower in the ND cohort than in the general population. Mortality from brain and other nervous system cancers was significantly higher in the ND cohort (SMR, 3.82; 95% CI, 1.04-9.77). Whereas point estimates were greater for all neurodegenerative causes (SMR, 1.42; 95% CI, 0.29-4.18), amyotrophic lateral sclerosis (SMR, 2.93; 95% CI, 0.36-10.59), and Parkinson disease (SMR, 2.07; 95% CI, 0.05-11.55), the difference did not reach statistical significance.
    Conclusions and relevance: In this cohort study of former college football players, both positive and negative health outcomes were observed. With more than 800 000 former college players living in the US, additional research appears to be needed to provide stakeholders with guidance to maximize factors that improve health outcomes and minimize factors that may increase risk for later-life morbidity and mortality.
    MeSH term(s) Aged ; Brain Concussion/complications ; Brain Concussion/epidemiology ; Cohort Studies ; Female ; Football/injuries ; Humans ; Male ; Neurodegenerative Diseases ; Outcome Assessment, Health Care
    Language English
    Publishing date 2022-04-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2574-3805
    ISSN (online) 2574-3805
    DOI 10.1001/jamanetworkopen.2022.8775
    Database MEDical Literature Analysis and Retrieval System OnLINE

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