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  • 1
    Online Resource
    Online Resource
    Neuropsychological test performance of former American football players
    Springer Science and Business Media LLC ; 2023
    In:  Alzheimer's Research & Therapy Vol. 15, No. 1 ( 2023-01-03)
    Details
    In: Alzheimer's Research & Therapy, Springer Science and Business Media LLC, Vol. 15, No. 1 ( 2023-01-03)
    Abstract: Patterns of cognitive impairment in former American football players are uncertain because objective neuropsychological data are lacking. This study characterized the neuropsychological test performance of former college and professional football players. Methods One hundred seventy male former football players ( n =111 professional, n =59 college; 45–74 years) completed a neuropsychological test battery. Raw scores were converted to T -scores using age, sex, and education-adjusted normative data. A T -score ≤ 35 defined impairment. A domain was impaired if 2+ scores fell in the impaired range except for the language and visuospatial domains due to the limited number of tests. Results Most football players had subjective cognitive concerns. On testing, rates of impairments were greatest for memory (21.2% two tests impaired), especially for recall of unstructured (44.7%) versus structured verbal stimuli (18.8%); 51.8% had one test impaired. 7.1% evidenced impaired executive functions; however, 20.6% had impaired Trail Making Test B. 12.1% evidenced impairments in the attention, visual scanning, and psychomotor speed domain with frequent impairments on Trail Making Test A (18.8%). Other common impairments were on measures of language (i.e., Multilingual Naming Test [21.2%], Animal Fluency [17.1%] ) and working memory (Number Span Backward [14.7%]). Impairments on our tasks of visuospatial functions were infrequent. Conclusions In this sample of former football players (most of whom had subjective cognitive concerns), there were diffuse impairments on neuropsychological testing with verbal memory being the most frequently impaired domain.
    Type of Medium: Online Resource
    ISSN: 1758-9193
    URL: Article
    DOI: 10.1186/s13195-022-01147-9
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2506521-X
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  • 2
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    Online Resource
    Amyloid PET across the cognitive spectrum in former professional and college American football players: findings from the DIAGNOSE CTE Research Project
    Springer Science and Business Media LLC ; 2023
    In:  Alzheimer's Research & Therapy Vol. 15, No. 1 ( 2023-10-05)
    Details
    In: Alzheimer's Research & Therapy, Springer Science and Business Media LLC, Vol. 15, No. 1 ( 2023-10-05)
    Abstract: Exposure to repetitive head impacts (RHI) in American football players can lead to cognitive impairment and dementia due to neurodegenerative disease, particularly chronic traumatic encephalopathy (CTE). The pathognomonic lesion of CTE consists of perivascular aggregates of hyper-phosphorylated tau in neurons at the depths of cortical sulci. However, it is unclear whether exposure to RHI accelerates amyloid-β (Aβ) plaque formation and increases the risk for Alzheimer’s disease (AD). Although the Aβ neuritic plaques characteristic of AD are observed in a minority of later-stage CTE cases, diffuse plaques are more common. This study examined whether former professional and college American football players, including those with cognitive impairment and dementia, have elevated neuritic Aβ plaque density, as measured by florbetapir PET. Regardless of cognitive and functional status, elevated levels of florbetapir uptake were not expected. Methods We examined 237 men ages 45–74, including 119 former professional (PRO) and 60 former college (COL) football players, with and without cognitive impairment and dementia, and 58 same-age men without a history of contact sports or TBI (unexposed; UE) and who denied cognitive or behavioral symptoms at telephone screening. Former players were categorized into four diagnostic groups: normal cognition, subjective memory impairment, mild cognitive impairment, and dementia. Positive florbetapir PET was defined by cortical-cerebellar average SUVR of ≥ 1.10. Multivariable linear regression and analysis of covariance (ANCOVA) compared florbetapir average SUVR across diagnostic and exposure groups. Multivariable logistic regression compared florbetapir positivity. Race, education, age, and APOE4 were covariates. Results There were no diagnostic group differences either in florbetapir average SUVR or the proportion of elevated florbetapir uptake. Average SUVR means also did not differ between exposure groups: PRO-COL ( p  = 0.94, 95% C.I. = [− 0.033, 0.025]), PRO-UE ( p  = 0.40, 95% C.I. = [− 0.010, 0.029]), COL-UE ( p  = 0.36, 95% CI = [0.0004, 0.039]). Florbetapir was not significantly associated with years of football exposure, cognition, or daily functioning. Conclusions Cognitive impairment in former American football players is not associated with PET imaging of neuritic Aβ plaque deposition. These findings are inconsistent with a neuropathological diagnosis of AD in individuals with substantial RHI exposure and have both clinical and medico-legal implications. Trial registration NCT02798185.
    Type of Medium: Online Resource
    ISSN: 1758-9193
    URL: Article
    DOI: 10.1186/s13195-023-01315-5
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2506521-X
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  • 3
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    Online Resource
    Associations between near end-of-life flortaucipir PET and postmortem CTE-related tau neuropathology in six former American football players
    Springer Science and Business Media LLC ; 2023
    In:  European Journal of Nuclear Medicine and Molecular Imaging Vol. 50, No. 2 ( 2023-01), p. 435-452
    Details
    In: European Journal of Nuclear Medicine and Molecular Imaging, Springer Science and Business Media LLC, Vol. 50, No. 2 ( 2023-01), p. 435-452
    Abstract: Flourine-18-flortaucipir tau positron emission tomography (PET) was developed for the detection for Alzheimer’s disease. Human imaging studies have begun to investigate its use in chronic traumatic encephalopathy (CTE). Flortaucipir-PET to autopsy correlation studies in CTE are needed for diagnostic validation. We examined the association between end-of-life flortaucipir PET and postmortem neuropathological measurements of CTE-related tau in six former American football players. Methods Three former National Football League players and three former college football players who were part of the DIAGNOSE CTE Research Project died and agreed to have their brains donated. The six players had flortaucipir (tau) and florbetapir (amyloid) PET prior to death. All brains from the deceased participants were neuropathologically evaluated for the presence of CTE. On average, the participants were 59.0 (SD = 9.32) years of age at time of PET. PET scans were acquired 20.33 (SD = 13.08) months before their death. Using Spearman correlation analyses, we compared flortaucipir standard uptake value ratios (SUVRs) to digital slide-based AT8 phosphorylated tau (p-tau) density in a priori selected composite cortical, composite limbic, and thalamic regions-of-interest (ROIs). Results Four brain donors had autopsy-confirmed CTE, all with high stage disease ( n  = 3 stage III, n  = 1 stage IV). Three of these four met criteria for the clinical syndrome of CTE, known as traumatic encephalopathy syndrome (TES). Two did not have CTE at autopsy and one of these met criteria for TES. Concomitant pathology was only present in one of the non-CTE cases (Lewy body) and one of the CTE cases (motor neuron disease). There was a strong association between flortaucipir SUVRs and p-tau density in the composite cortical ( ρ  = 0.71) and limbic ( ρ  = 0.77) ROIs. Although there was a strong association in the thalamic ROI ( ρ  = 0.83), this is a region with known off-target binding. SUVRs were modest and CTE and non-CTE cases had overlapping SUVRs and discordant p-tau density for some regions. Conclusions Flortaucipir-PET could be useful for detecting high stage CTE neuropathology, but specificity to CTE p-tau is uncertain. Off-target flortaucipir binding in the hippocampus and thalamus complicates interpretation of these associations. In vivo biomarkers that can detect the specific p-tau of CTE across the disease continuum are needed.
    Type of Medium: Online Resource
    ISSN: 1619-7070 , 1619-7089
    URL: Article
    DOI: 10.1007/s00259-022-05963-x
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2098375-X
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