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  • 1
    In: Alzheimer's Research & Therapy, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2021-12)
    Abstract: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that has been neuropathologically diagnosed in brain donors exposed to repetitive head impacts, including boxers and American football, soccer, ice hockey, and rugby players. CTE cannot yet be diagnosed during life. In December 2015, the National Institute of Neurological Disorders and Stroke awarded a seven-year grant (U01NS093334) to fund the “Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy (DIAGNOSE CTE) Research Project.” The objectives of this multicenter project are to: develop in vivo fluid and neuroimaging biomarkers for CTE; characterize its clinical presentation; refine and validate clinical research diagnostic criteria (i.e., traumatic encephalopathy syndrome [TES]); examine repetitive head impact exposure, genetic, and other risk factors; and provide shared resources of anonymized data and biological samples to the research community. In this paper, we provide a detailed overview of the rationale, design, and methods for the DIAGNOSE CTE Research Project. Methods The targeted sample and sample size was 240 male participants, ages 45–74, including 120 former professional football players, 60 former collegiate football players, and 60 asymptomatic participants without a history of head trauma or participation in organized contact sports. Participants were evaluated at one of four U.S. sites and underwent the following baseline procedures: neurological and neuropsychological examinations; tau and amyloid positron emission tomography; magnetic resonance imaging and spectroscopy; lumbar puncture; blood and saliva collection; and standardized self-report measures of neuropsychiatric, cognitive, and daily functioning. Study partners completed similar informant-report measures. Follow-up evaluations were intended to be in-person and at 3 years post-baseline. Multidisciplinary diagnostic consensus conferences are held, and the reliability and validity of TES diagnostic criteria are examined. Results Participant enrollment and all baseline evaluations were completed in February 2020. Three-year follow-up evaluations began in October 2019 . However, in-person evaluation ceased with the COVID-19 pandemic, and resumed as remote, 4-year follow-up evaluations (including telephone-, online-, and videoconference-based cognitive, neuropsychiatric, and neurologic examinations, as well as in-home blood draw) in February 2021. Conclusions Findings from the DIAGNOSE CTE Research Project should facilitate detection and diagnosis of CTE during life, and thereby accelerate research on risk factors, mechanisms, epidemiology, treatment, and prevention of CTE. Trial registration NCT02798185
    Type of Medium: Online Resource
    ISSN: 1758-9193
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2506521-X
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  • 2
    In: eBioMedicine, Elsevier BV, Vol. 97 ( 2023-11), p. 104820-
    Type of Medium: Online Resource
    ISSN: 2352-3964
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2799017-5
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  • 3
    In: BMC Medical Genetics, Springer Science and Business Media LLC, Vol. 8, No. S1 ( 2007-9)
    Type of Medium: Online Resource
    ISSN: 1471-2350
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2007
    detail.hit.zdb_id: 2041359-2
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  • 4
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2006
    In:  Stroke Vol. 37, No. 2 ( 2006-02), p. 345-350
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 37, No. 2 ( 2006-02), p. 345-350
    Abstract: Background and Purpose— The lifetime risk (LTR) of stroke has not been reported for the United States population; such data would assist public education and health planning. Methods— Framingham Original cohort participants (n=4897) who were stroke- and dementia-free at 55 years of age were followed biennially for up to 51 years (115 146 person years). We estimated the sex-specific 10-, 20-, and 30-year risks and LTR of developing a stroke by baseline age and blood pressure (BP) and compared it with the risk of developing Alzheimer disease (AD). Results— A total of 875 participants (522 women) developed a first-ever stroke; 749 (448 women) had an ischemic stroke. LTR of stroke was high and remained similar at ages 55, 65, and 75 years, approximating 1 in 5 for women and 1 in 6 for men. Participants with a normal BP ( 〈 120/80 mm Hg) had approximately half the LTR of stroke compared with those with high BP (≥140/90 mm Hg). The LTR of AD at age 65 (292 participants; 211 women) approximated 1 in 5 for women and 1 in 10 for men. The LTR of developing either stroke or dementia approximated 1 in 3 in both sexes. Conclusion— The LTR of stroke in middle-aged adults is 1 in 6 or more, which is equal to or greater than the LTR of AD. Women had a higher risk because of longer life expectancy. BP is a significant determinant of the LTR of stroke, and promotion of normal BP levels in the community might be expected to substantially reduce this risk.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2006
    detail.hit.zdb_id: 1467823-8
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  • 5
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 41, No. 4 ( 2010-04), p. 600-606
    Abstract: Background and Purpose— White matter hyperintensities and MRI-defined brain infarcts (BIs) have individually been related to stroke, dementia, and mortality in population-based studies, mainly in older people. Their significance in middle-aged community-dwelling persons and the relative importance of these associations remain unclear. We simultaneously assessed the relation of white matter hyperintensities and BI with incident stroke, mild cognitive impairment, dementia, and mortality in a middle-aged community-based cohort. Methods— A total of 2229 Framingham Offspring Study participants aged 62±9 years underwent volumetric brain MRI and neuropsychological testing (1999 to 2005). Incident stroke, dementia, and mortality were prospectively ascertained and for 1694 participants in whom a second neuropsychological assessment was performed (2005 to 2007), incident mild cognitive impairment was evaluated. All outcomes were related to white matter hyperintensities volume (WMHV), age-specific extensive WMHV and BI adjusting for age and gender. Results— Extensive WMHV and BI were associated with an increased risk of stroke (hazard ratio [HR]=2.28, 95% CI: 1.02 to 5.13; HR=2.84, 95% CI: 1.32 to 6.10). WMHV, extensive WMHV, and BI were associated with an increased risk of dementia (HR=2.22, 95% CI: 1.32 to 3.72; HR=3.97, 95% CI: 1.10 to 14.30; HR=6.12, 95% CI: 1.82 to 20.54) independently of vascular risk factors and interim stroke. WMHV and extensive WMHV were associated with incident amnestic mild cognitive impairment in participants aged ≥60 years only (OR=2.47, 95% CI: 1.31 to 4.66 and OR=1.49, 95% CI: 1.14 to 1.97). WMHV and extensive WMHV were associated with an increased risk of death (HR=1.38, 95% CI: 1.13 to 1.69; HR=2.27, 95% CI: 1.41 to 3.65) independent of vascular risk factors and of interim stroke and dementia. Conclusions— In a large community-based sample of middle-aged adults, BI predicted an increased risk of stroke and dementia independent of vascular risk factors. White matter hyperintensities portended an increased risk of stroke, amnestic mild cognitive impairment, dementia, and death independent of vascular risk factors and interim vascular events.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2010
    detail.hit.zdb_id: 1467823-8
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  • 6
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2004
    In:  Stroke Vol. 35, No. 6 ( 2004-06), p. 1264-1268
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 35, No. 6 ( 2004-06), p. 1264-1268
    Abstract: Background and Purpose— Identification of risk factors for dementia after stroke is best performed in comparison with stroke-free controls, because older subjects at high risk for stroke also have a substantial risk of dementia in the absence of stroke. Previous case-control studies were hospital-based. We used a nested case-control design to prospectively evaluate these risk factors in the community-based Framingham Study cohort. Methods— We compared 212 subjects who were free of dementia in January 1982 and sustained a first stroke after this date, with 1060 age- and sex-matched, stroke- and dementia-free controls. We calculated 10-year risks of dementia (by Diagnostic and Statistical Manual of Mental Disorders , Volume IV criteria) developing in cases and controls and also estimated the hazard ratios within subgroups defined by exposure to various demographic factors (age, gender, education), stroke-related features (right or left hemisphere, stroke type, second stroke), stroke risk factors (hypertension, diabetes, atrial fibrillation, smoking) and apolipoprotein E genotype. Results— Dementia developed in 19.3% of cases and 11.0% of controls. Baseline stroke doubled the risk of dementia (hazard ratio [HR]: 2.0; 95% confidence interval [CI] : 1.5 to 3.1) and adjustment for age, sex, education, and exposure to individual stroke risk factors did not diminish the risk (HR: 2.4; 95% CI: 1.6 to 3.7). The HR was higher in younger subjects (age younger than 80 years [HR: 2.6; 95% CI: 1.5 to 4.5]), apolipoprotein E 3/3 homozygotes (HR: 3.4; 95% CI: 2.0 to 5.8), and high school graduates (HR: 2.4; 95% CI: 1.5 to 3.9). Conclusion— Stroke increases a subject’s risk of dementia as compared with age- and sex-matched controls. Primary and secondary prevention of stroke should significantly decrease the risk of all dementia.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2004
    detail.hit.zdb_id: 1467823-8
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  • 7
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 43, No. suppl_1 ( 2012-02)
    Abstract: Objectives- Parental stroke is related to an increased risk of stroke among the offspring. Vascular related brain changes, however, often occur before clinical stroke and the association of parental history of stroke and structural brain measures and cognition has not been fully explored. We hypothesized that prospectively verified parental stroke will be associated with increased vascular brain injury and poorer cognitive performance. Methods- A total of 1,297 Framingham offspring (mean age: 61 ± 9 years, 54% women) were studied. Of these, 9.9% had prospectively identified stroke in one or both parents before age 65. Volumetric brain MRI measures of total cerebral brain volume (TCBV), regional brain volumes, white matter hyperintensity volume (WMHV), and covert brain infarcts (CBI) and performance on tests of verbal memory, abstract reasoning, verbal learning and visuospatial memory (VRd) were compared for offspring with and without parental history of stroke. All measures were assessed cross-sectionally and longitudinally (mean duration of follow-up was 6.1±1.2 years). We used models adjusted only for age, sex, education and also additionally adjusted for vascular risk factors and for WMHV as an index of subclinical vascular brain injury. GEE models were used to adjust for sibling relationships among offspring. Results- Higher WMHV (β±SE=0.17±0.08;p=0.027) and lower VRd scores (β±SE=-0.80±0.34; p=0.017) at baseline were found in offspring with parental history of stroke. In addition, participants with parental stroke by age 65 years were more likely to be in the highest quintile of increase in WMHV (OR=1.87;p=0.04) as well as worsening executive function (Trails B-A) (OR:1.81;p=0.03). Parental stroke was not associated with total and regional brain volumes or with memory, abstract reasoning and verbal learning. Conclusions- In our community-based sample of middle-aged asymptomatic subjects, the occurrence of parental stroke by age 65 years is associated with higher baseline WMHV and with a more rapid increase in WMHV. Further, parental stroke is also associated with poorer performance on VRd and a decline in executive function. The effects on baseline WMH and VRd were substantial equivalent to 2.8 and 7 years of brain aging, respectively.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
    detail.hit.zdb_id: 1467823-8
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  • 8
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2001
    In:  Stroke Vol. 32, No. suppl_1 ( 2001-01), p. 362-362
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 32, No. suppl_1 ( 2001-01), p. 362-362
    Abstract: P131 Background: MRI Abnormalities of cerebral white matter (WMH) are associated with multiple cerebral vascular risk factors, such as hypertension. The association between WMH and risk for stroke, however, has been investigated only in a limited fashion. The Framingham stroke risk profile (FSRP), based on information from the original Framingham Study Cohort (FHS), has been shown to estimate age- and gender specific probability of stroke in a number of populations. To test the utility of WMH to predict future stroke, we related the FSRP to WMH in 909 offspring of the original FHS (FHS o ) who were free of clinical stroke. Methods: Quantification of MRI WMH was performed in the years 1999–2000 on 919 individuals of the FHS o who had taken Exam 5 during 1991–95 when they were ages 35–74 (mean age 55 ±9 years). None were demented. Data from 10 individuals with prior stroke were excluded. FSRP was computed using Exam 5 risk factor data. Using linear regression, age-related differences in WMH volume, corrected for differences in head size, were computed. WMH volumes 〉 1 sd above the age-predicted mean were considered large. Analyses employed T-test comparison according to WMH category (large vs normal) as well as multiple logistic regression analysis to predict category. Results: 43 individuals (4.7%) were identified as having large volumes of WMH. These individuals had significantly higher SBP (132 ±19 mmHg vs 124 ±18 mmHg; p=0.003) and significantly higher FSRP (0.070 ±0.057 versus 0.040 ±0.043; p=0.002) at Exam 5. Using logistic regression, the odds of having large WMH volumes increased by 1.26 (95% CL 1.08–1.48; p=0.004) for each 10mmHg increase of SBP and 1.09 (95% CL 1.05–1.14; p=0.001) for each 1% increase in FSRP. Analysis by gender showed a similar pattern although SBP did not reach statistical significance for WMH in women (128.4 +19.1 versus 121.7 +18.7, p=0.068). Conclusion: Large WMH are seen in men and women with previously measured, significantly increased predicted stroke risk. Further prospective evaluation will be important to determine if the extent of WMH is a predictor of risk for stroke as suggested by the increased values of FSRP amongst those with large WMH.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2001
    detail.hit.zdb_id: 1467823-8
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  • 9
    Online Resource
    Online Resource
    Elsevier BV ; 2020
    In:  The American Journal of Geriatric Psychiatry Vol. 28, No. 6 ( 2020-06), p. 591-596
    In: The American Journal of Geriatric Psychiatry, Elsevier BV, Vol. 28, No. 6 ( 2020-06), p. 591-596
    Type of Medium: Online Resource
    ISSN: 1064-7481
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 1474415-6
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  • 10
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2013
    In:  Stroke Vol. 44, No. 10 ( 2013-10), p. 2787-2794
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 44, No. 10 ( 2013-10), p. 2787-2794
    Abstract: Exposure to vascular risk factors has a gradual deleterious effect on brain MRI and cognitive measures. We explored whether a pattern of these measures exists that predicts stroke and Alzheimer disease (AD) risk. Methods— A cognitive battery was administered to 1679 dementia and stroke-free Framingham offspring (age, 〉 55 years; mean, 65.7±7.0) between 1999 and 2004; participants were also free of other neurological conditions that could affect cognition and 〉 90% also had brain MRI examination. We related cognitive and MRI measures to risks of incident stroke and AD ≤10 years of follow-up. As a secondary analysis, we explored these associations in The Framingham Heart Study original cohort (mean age, 67.5±7.3 and 84.8±3.3 years at the cognitive assessment and MRI examination, respectively). Results— A total of 55 Offspring participants sustained strokes and 31 developed AD. Offspring who scored 〈 1.5 SD below predicted mean scores, for age and education, on an executive function test, had a higher risk of future stroke (hazard ratio [HR], 2.27; 95% confidence interval [CI] , 1.06–4.85) and AD (HR, 3.60; 95% CI, 1.52–8.52); additional cognitive tests also predicted AD. Participants with low ( 〈 20 percentile) total brain volume and high ( 〉 20 percentile) white matter hyperintensity volume had a higher risk of stroke (HR, 1.97; 95% CI, 1.03–3.77 and HR, 2.74; 95% CI, 1.51–5.00, respectively) but not AD. Hippocampal volume at the bottom quintile predicted AD in the offspring and original cohorts (HR, 4.41; 95% CI, 2.00–9.72 and HR, 2.37; 95% CI, 1.12–5.00, respectively). A stepwise increase in stroke risk was apparent with increasing numbers of these cognitive and imaging markers. Conclusions— Specific patterns of cognitive and brain structural measures observed even in early aging predict stroke risk and may serve as biomarkers for risk prediction.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
    detail.hit.zdb_id: 1467823-8
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