Publications by authors named "Jesse Mez"

Chronic traumatic encephalopathy (CTE) is a progressive brain disease linked to repetitive head impacts (RHI), often incurred from contact sports, and can lead to dementia. Here, we investigated the association between RHI and white matter/vascular neuropathologies and their relative contribution to dementia status in deceased men 50 + years old with and without exposure to RHI from various types of contact and collision sports. Our sample included two RHI groups from the UNITE brain bank: (1) American Football players (RHI-AF, n = 79), and (2) non-AF contact and collision sport athletes (e.

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Objective: The Cantu Concussion Summit aimed to gather clinicians and researchers to share findings and identify research gaps in brain injury and long-term cognitive disorders in athletes.

Design: The conference concluded with a discussion of ways to best mitigate the risk of concussion and repetitive traumatic brain injury (RTBI).

Setting And Participants: The summit was supported by an unrestricted educational grant from the National Football League and featured a diverse group of experts from multiple disciplines.

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Background: Molecular biomarkers of chronic traumatic encephalopathy (CTE) are lacking. We evaluated F-MK-6240 tau PET as a biomarker for CTE. Two studies were done: (1) H-MK-6240 autoradiography and an in-vitro brain homogenate binding studies on postmortem CTE tissue, (2) an in-vivo F-MK-6240 tau PET study in former American football players.

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Background: Genome-wide association studies (GWAS) have identified over 1,000 blood pressure (BP) loci and over 80 loci for Alzheimer's disease (AD). Considering BP is an AD risk factor, identifying pleiotropy in BP and cognitive performance measures may indicate mechanistic links between BP and AD.

Methods: Genome-wide scans for pleiotropy in BP variables-systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse pressure (PP)-and co-calibrated scores for cognitive domains (executive function, language, and memory) were performed using generalized linear mixed models and 116,075 longitudinal measures from 25,726 participants of clinic-based and prospective cohorts.

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Exposure to repetitive head impacts (RHI), such as those experienced in American football, is linked to cognitive dysfunction later in life. Traumatic encephalopathy syndrome (TES) is a proposed clinical syndrome thought to be linked to neuropath-ology of chronic traumatic encephalopathy (CTE), a condition associated with RHI from football. Cognitive intra-individual variability (d-CIIV) measures test-score dispersion, indicating cognitive dysfunction.

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 Cognitive impairment is a core feature of traumatic encephalopathy syndrome (TES), the putative clinical syndrome of chronic traumatic encephalopathy-a neuropathological disease associated with repetitive head impacts (RHI). Careful operationalization of cognitive impairment is essential to improving the diagnostic specificity and accuracy of TES criteria. We compared single- versus two-test criteria for cognitive impairment in their associations with CSF and imaging biomarkers in male former American football players.

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Importance: "SuperAgers" are oldest-old adults (ages 80+) whose memory performance resembles that of adults in their 50s to mid-60s. Factors underlying their exemplary memory are underexplored in large, racially diverse cohorts.

Objective: To determine the frequency of genotypes in non-Hispanic Black and non-Hispanic White SuperAgers compared to middle-aged (ages 50-64), old (ages 65-79), and oldest-old (ages 80+) controls and Alzheimer's disease (AD) dementia cases.

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Introduction: Accurately assessing temporal order of cognitive decline across multiple domains is critical in Alzheimer's disease (AD). Existing literature presented controversial conclusions likely due to the use of a single cohort and different analytical strategies.

Methods: Harmonized composite cognitive measures in memory, language and executive functions from 13 cohorts in the ADSP-PHC data are used.

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Introduction: Alzheimer's disease (AD), primary age-related tauopathy (PART), and chronic traumatic encephalopathy (CTE) all feature hyperphosphorylated tau (p-tau)-immunoreactive neurofibrillary degeneration, but differ in neuroanatomical distribution and progression of neurofibrillary degeneration and amyloid beta (Aβ) deposition.

Methods: We used Nanostring GeoMx Digital Spatial Profiling to compare the expression of 70 proteins in neurofibrillary tangle (NFT)-bearing and non-NFT-bearing neurons in hippocampal CA1, CA2, and CA4 subregions and entorhinal cortex of cases with autopsy-confirmed AD (n = 8), PART (n = 7), and CTE (n = 5).

Results: There were numerous subregion-specific differences related to Aβ processing, autophagy/proteostasis, inflammation, gliosis, oxidative stress, neuronal/synaptic integrity, and p-tau epitopes among these different disorders.

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Former American football players are at risk for developing traumatic encephalopathy syndrome (TES), the clinical disorder associated with neuropathologically diagnosed chronic traumatic encephalopathy (CTE). The objective of this study was to determine whether hyposmia is present in traumatic encephalopathy syndrome. The study included 119 former professional American football players, 60 former college football players, and 58 same-age asymptomatic unexposed men from the DIAGNOSE CTE Research Project.

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Neurodegeneration is a seminal feature of many neurological disorders. Chronic traumatic encephalopathy (CTE) is caused by repetitive head impacts (RHI) and is characterized by sulcal tau pathology. However, quantitative assessments of regional neurodegeneration in CTE have not been described.

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Importance: Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with repetitive head impacts (RHIs). Prior research suggests a dose-response association between American football play duration and CTE risk and severity, but this association has not been studied for ice hockey.

Objective: To investigate associations of duration of ice hockey play with CTE diagnosis and severity, functional status, and dementia.

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Article Synopsis
  • Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to frequent head injuries, often seen in athletes and military personnel, with a focus on its relationship with aggression and family mental health history.
  • The study analyzed data from deceased male brain donors with CTE, aiming to determine if the presence of CTE affects the relationship between first-degree family history of mental illness (1°FHMI) and aggression, using structured assessments and various demographic controls.
  • Results indicated that 1°FHMI was significantly correlated with aggression scores in individuals with CTE, suggesting that CTE pathology may influence aggression differently than previously understood, while no such association was found in those without CTE.
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  • Limited research has examined how cardiovascular risk and amyloid levels influence cognitive decline in East Asians, specifically in a study involving 526 participants from the Korean Brain Aging Study.
  • Results showed that cognitively normal individuals without amyloid (Aβ-) but with high cardiovascular risk scores had significantly lower cognitive performance than their low-risk counterparts.
  • Ultimately, while managing vascular risk is important for early cognitive preservation in Aβ- individuals, amyloid pathology was found to be the main factor driving cognitive decline in both cognitively normal and mild cognitive impairment groups, regardless of vascular risk status.
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Background And Objectives: CSF biomarkers of Aβ42 and phosphorylated tau (p-tau181) are used clinically for the detection of Alzheimer disease (AD) pathology during life. CSF biomarker validation studies have largely used clinical diagnoses and/or amyloid PET imaging as the reference standard. The few existing CSF-to-autopsy studies have been restricted to late-stage AD.

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Article Synopsis
  • The study investigates how cardiovascular risk factors relate to the risk of developing all-cause dementia and Alzheimer's disease, with a focus on sex differences.
  • Data from the Framingham Heart Study involving over 4,000 participants showed that high Framingham Stroke Risk Profile (FSRP) scores significantly increase the risk of dementia and Alzheimer's, especially in women.
  • The findings highlight the need for sex-specific interventions and further research to understand the mechanisms behind these associations.
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Article Synopsis
  • - Blood-based biomarkers are being explored to detect brain injuries from repetitive head impacts, specifically in former football players, by analyzing plasma levels of various proteins like tau and amyloid.
  • - A study involving 180 former football players and 60 control participants found that specific biomarkers (p-tau181 and p-tau231) were significantly elevated in the football players, indicating potential brain damage linked to their sport.
  • - The findings suggest that certain plasma proteins (p-tau, GFAP, NfL) could help in understanding and identifying neurological issues related to head impacts, with younger players showing more severe biomarker changes.
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Background: Former professional collision sport (CS) athletes, particularly American football players, are at risk of developing chronic health conditions; however, little is known about the health outcomes of amateur athletes.

Methods: A 60-item health survey examined self-reported symptoms and diagnoses among former Division 1 Collegiate CS athletes and non- or limited-contact sport (non-CS) athletes. Binary logistic regressions tested the association between playing CS and health outcomes.

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Introduction: Brain magnetic resonance imaging (MRI) and inflammatory biomarkers are crucial for investigating preclinical neurocognitive disorders. Current investigations focus on a few inflammatory markers. The study aims to investigate the associations between inflammatory biomarkers and MRI measures and to examine sex differences among the associations in the Framingham Heart Study.

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Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy more frequently found in deceased former football players. CTE has heterogeneous clinical presentations with multifactorial causes. Previous literature has shown substance use (alcohol/drug) can contribute to Alzheimer's disease and related tauopathies pathologically and clinically.

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Article Synopsis
  • Some sports and repeated head injuries (like playing football) might lead to brain problems later in life, especially conditions like Frontotemporal Dementia (FTD) and Primary Progressive Aphasia (PPA).
  • Researchers compared people with FTD/PPA to healthy ones to see how many had Traumatic Brain Injuries (TBI) and head impacts.
  • They found that people with FTD/PPA had more sports experience causing head impacts, and those with a history of head injuries had symptoms show up earlier than those without.
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  • The study investigates the relationship between perivascular space (PVS) volume in the brain and lifetime exposure to repetitive head impacts (RHI) in individuals at risk for neurodegenerative diseases, particularly focusing on former American football players.
  • Conducted across four US study sites from 2016 to 2020, the research involved 224 participants, including 170 former football players and 54 control participants, with analyses exploring how PVS volume correlates with cognitive impairment.
  • Results showed that former football players exhibited larger PVS volumes compared to the control group, suggesting that RHI exposure could contribute to changes in brain structure associated with neurodegeneration.
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Background: Cerebral microbleeds (CMB) increase the risk for Alzheimer disease. Current neuroimaging methods that are used to detect CMB are costly and not always accessible.

Objective: This study aimed to explore whether the digital clock-drawing test (DCT) may provide a behavioral indicator of CMB.

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  • Parkinsonism is often linked to chronic traumatic encephalopathy (CTE) caused by repetitive head injuries, but the exact causes of parkinsonism in CTE patients are not fully understood.
  • This study examined brain donors diagnosed with CTE to determine how often parkinsonism occurs and its relationship with brain damage due to past sports-related injuries.
  • Results indicated that 24.7% of CTE participants experienced parkinsonism, which was associated with older age, higher dementia rates, and more severe stages of CTE, suggesting a significant connection between the severity of CTE and parkinsonism.
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Background: Neuropsychiatric symptoms (NPS) can be an early manifestation of Alzheimer's disease (AD). However, the associations among NPS, cognition, and AD biomarkers across the disease spectrum are unclear.

Objective: We analyzed cross-sectional mediation pathways between cerebrospinal fluid (CSF) biomarkers of AD (Aβ1-42, p-tau181), cognitive function, and NPS.

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