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  • 1
    In: European Journal of Nuclear Medicine and Molecular Imaging, Springer Science and Business Media LLC, Vol. 50, No. 2 ( 2023-01), p. 435-452
    Kurzfassung: 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.
    Materialart: Online-Ressource
    ISSN: 1619-7070 , 1619-7089
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2023
    ZDB Id: 2098375-X
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  • 2
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    Oxford University Press (OUP) ; 2009
    In:  Archives of Clinical Neuropsychology Vol. 24, No. 5 ( 2009-08-01), p. 431-540
    In: Archives of Clinical Neuropsychology, Oxford University Press (OUP), Vol. 24, No. 5 ( 2009-08-01), p. 431-540
    Materialart: Online-Ressource
    ISSN: 0887-6177 , 1873-5843
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2009
    ZDB Id: 2003528-7
    SSG: 5,2
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  • 3
    Online-Ressource
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    Oxford University Press (OUP) ; 2010
    In:  Archives of Clinical Neuropsychology Vol. 25, No. 6 ( 2010-09-01), p. 475-583
    In: Archives of Clinical Neuropsychology, Oxford University Press (OUP), Vol. 25, No. 6 ( 2010-09-01), p. 475-583
    Materialart: Online-Ressource
    ISSN: 0887-6177 , 1873-5843
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2010
    ZDB Id: 2003528-7
    SSG: 5,2
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    In: Alzheimer's Research & Therapy, Springer Science and Business Media LLC, Vol. 15, No. 1 ( 2023-10-05)
    Kurzfassung: 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.
    Materialart: Online-Ressource
    ISSN: 1758-9193
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2023
    ZDB Id: 2506521-X
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    In: Alzheimer's Research & Therapy, Springer Science and Business Media LLC, Vol. 15, No. 1 ( 2023-01-03)
    Kurzfassung: 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.
    Materialart: Online-Ressource
    ISSN: 1758-9193
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2023
    ZDB Id: 2506521-X
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    Online-Ressource
    Online-Ressource
    Springer Science and Business Media LLC ; 2017
    In:  Translational Psychiatry Vol. 7, No. 9 ( 2017-09-19), p. e1236-e1236
    In: Translational Psychiatry, Springer Science and Business Media LLC, Vol. 7, No. 9 ( 2017-09-19), p. e1236-e1236
    Kurzfassung: Previous research suggests that age of first exposure (AFE) to football before age 12 may have long-term clinical implications; however, this relationship has only been examined in small samples of former professional football players. We examined the association between AFE to football and behavior, mood and cognition in a large cohort of former amateur and professional football players. The sample included 214 former football players without other contact sport history. Participants completed the Brief Test of Adult Cognition by Telephone (BTACT), and self-reported measures of executive function and behavioral regulation (Behavior Rating Inventory of Executive Function-Adult Version Metacognition Index (MI), Behavioral Regulation Index (BRI)), depression (Center for Epidemiologic Studies Depression Scale (CES-D)) and apathy (Apathy Evaluation Scale (AES)). Outcomes were continuous and dichotomized as clinically impaired. AFE was dichotomized into 〈 12 and ⩾12, and examined continuously. Multivariate mixed-effect regressions controlling for age, education and duration of play showed AFE to football before age 12 corresponded with 〉 2 × increased odds for clinically impaired scores on all measures but BTACT: (odds ratio (OR), 95% confidence interval (CI): BRI, 2.16,1.19–3.91; MI, 2.10,1.17–3.76; CES-D, 3.08,1.65–5.76; AES, 2.39,1.32–4.32). Younger AFE predicted increased odds for clinical impairment on the AES (OR, 95% CI: 0.86, 0.76–0.97) and CES-D (OR, 95% CI: 0.85, 0.74–0.97). There was no interaction between AFE and highest level of play. Younger AFE to football, before age 12 in particular, was associated with increased odds for impairment in self-reported neuropsychiatric and executive function in 214 former American football players. Longitudinal studies will inform youth football policy and safety decisions.
    Materialart: Online-Ressource
    ISSN: 2158-3188
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2017
    ZDB Id: 2609311-X
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  • 7
    Online-Ressource
    Online-Ressource
    Elsevier BV ; 1982
    In:  Human Immunology Vol. 5, No. 2 ( 1982-10), p. 158-
    In: Human Immunology, Elsevier BV, Vol. 5, No. 2 ( 1982-10), p. 158-
    Materialart: Online-Ressource
    ISSN: 0198-8859
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 1982
    ZDB Id: 2006465-2
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
    In: Transfusion, Wiley, Vol. 26, No. 5 ( 1986-09-10), p. 446-452
    Kurzfassung: Per procedure, plateletapheresis may remove 2×10 9 to 3×10 9 white cells from the peripheral blood of a normal donor. To investigate the effects of frequent and sustained plateletapheresis, multiple peripheral blood tests were performed on 25 volunteer donors undergoing plateletapheresis an average of 72 times over periods of up to 8 years, and results were compared with 25 age‐ and sex‐matched controls who had not undergone apheresis. In donors, significant decreases were observed in: 1) both absolute number and percentage of T4+ cells; 2) absolute number of both T8+ cells and LeU‐7+ cells; 3) T4/T8 ratio; 4) responses to both pokeweed mitogen and alloantigens; and 5) IgG levels. Significant increases were observed in percentages of both B cells and monocytes, and responses to both phytohemagglutinin and Concanavalin A. Plateletapheresis removes a large number of T4 and T8 cells, a moderate number of B cells, and a smaller number of monocytes and Leu‐7 cells. The results suggest that during vigorous plateletapheresis the replenishment to peripheral blood per month was less than 1.83×10 9 and 0.93×10 9 for T4 cells and T8 cells, respectively, greater than 0.27×10 9 and 0.62×10 9 for B cells and monocytes, respectively, and approximately 0.39×10 9 for Leu‐7 cells. Although no clinical effect was noted, these data suggest that frequent and sustained non‐lymphocyte sparing plateletapheresis is associated with changes in laboratory findings related to the immune system.
    Materialart: Online-Ressource
    ISSN: 0041-1132 , 1537-2995
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 1986
    ZDB Id: 2018415-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    In: Journal of Neurotrauma, Mary Ann Liebert Inc, Vol. 40, No. 3-4 ( 2023-02-01), p. 309-317
    Materialart: Online-Ressource
    ISSN: 0897-7151 , 1557-9042
    Sprache: Englisch
    Verlag: Mary Ann Liebert Inc
    Publikationsdatum: 2023
    ZDB Id: 2030888-7
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  • 10
    In: Brain, Oxford University Press (OUP), Vol. 145, No. 10 ( 2022-10-21), p. 3546-3557
    Kurzfassung: Blood-based biomarkers such as tau phosphorylated at threonine 181 (phosphorylated-tau181) represent an accessible, cost-effective and scalable approach for the in vivo detection of Alzheimer’s disease pathophysiology. Plasma-pathological correlation studies are needed to validate plasma phosphorylated-tau181 as an accurate and reliable biomarker of Alzheimer’s disease neuropathological changes. This plasma-to-autopsy correlation study included participants from the Boston University Alzheimer’s Disease Research Center who had a plasma sample analysed for phosphorylated-tau181 between 2008 and 2018 and donated their brain for neuropathological examination. Plasma phosphorelated-tau181 was measured with single molecule array technology. Of 103 participants, 62 (60.2%) had autopsy-confirmed Alzheimer’s disease. Average time between blood draw and death was 5.6 years (standard deviation = 3.1 years). Multivariable analyses showed higher plasma phosphorylated-tau181 concentrations were associated with increased odds for having autopsy-confirmed Alzheimer’s disease [AUC = 0.82, OR = 1.07, 95% CI = 1.03–1.11, P & lt; 0.01; phosphorylated-tau standardized (z-transformed): OR = 2.98, 95% CI = 1.50–5.93, P & lt; 0.01]. Higher plasma phosphorylated-tau181 levels were associated with increased odds for having a higher Braak stage (OR = 1.06, 95% CI = 1.02–1.09, P & lt; 0.01) and more severe phosphorylated-tau across six cortical and subcortical brain regions (ORs = 1.03–1.06, P & lt; 0.05). The association between plasma phosphorylated-tau181 and Alzheimer’s disease was strongest in those who were demented at time of blood draw (OR = 1.25, 95%CI = 1.02–1.53), but an effect existed among the non-demented (OR = 1.05, 95% CI = 1.01–1.10). There was higher discrimination accuracy for Alzheimer’s disease when blood draw occurred in years closer to death; however, higher plasma phosphorylated-tau181 levels were associated with Alzheimer’s disease even when blood draw occurred & gt;5 years from death. Ante-mortem plasma phosphorylated-tau181 concentrations were associated with Alzheimer’s disease neuropathology and accurately differentiated brain donors with and without autopsy-confirmed Alzheimer’s disease. These findings support plasma phosphorylated-tau181 as a scalable biomarker for the detection of Alzheimer’s disease.
    Materialart: Online-Ressource
    ISSN: 0006-8950 , 1460-2156
    RVK:
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2022
    ZDB Id: 1474117-9
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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