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- Sweeney, M. D., et al.
(author)
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Vascular dysfunction-The disregarded partner of Alzheimer's disease
- 2019
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In: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 15:1, s. 158-167
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Journal article (peer-reviewed)abstract
- Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging-Alzheimer's Association describes a biomarker-based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology. Next, we examined various imaging sequences that could be easily implemented to evaluate different types of vascular dysfunction associated with, and/or contributing to, AD pathophysiology, including changes in blood-brain barrier integrity and cerebral blood flow. Vascular imaging biomarkers of small vessel disease of the brain, which is responsible for >50% of dementia worldwide, including AD, are already established, well characterized, and easy to recognize. We suggest that these vascular biomarkers should be incorporated into the AD Research Framework to gain a better understanding of AD pathophysiology and aid in treatment efforts. (C) 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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| 3. |
- Taal, H. Rob, et al.
(author)
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Common variants at 12q15 and 12q24 are associated with infant head circumference
- 2012
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:5, s. 532-538
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Journal article (peer-reviewed)abstract
- To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
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| 4. |
- Ikram, M. Arfan, et al.
(author)
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Common variants at 6q22 and 17q21 are associated with intracranial volume
- 2012
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:5, s. 539-544
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Journal article (peer-reviewed)abstract
- During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study (GWAS) in 8,175 community-dwelling elderly persons did not reveal any associations at genome-wide significance (P < 5 x 10(-8)) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (P = 3.4 x 10(-11)), a known height-associated locus on chromosome 6q22, and rs9915547 (P = 1.5 x 10(-12)), localized to the inversion on chromosome 17q21. We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 elderly persons (P = 1.1 x 10(-3) for 6q22 and 1.2 x 10(-3) for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age of 14.5 months). Our data identify two loci associated with head size, with the inversion at 17q21 also likely to be involved in attaining maximal brain size.
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| 5. |
- Düzel, E., et al.
(author)
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European Ultrahigh-Field Imaging Network for Neurodegenerative Diseases (EUFIND)
- 2019
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In: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - : Wiley. - 2352-8729. ; 11, s. 538-549
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Journal article (peer-reviewed)abstract
- Introduction: The goal of European Ultrahigh-Field Imaging Network in Neurodegenerative Diseases (EUFIND) is to identify opportunities and challenges of 7 Tesla (7T) MRI for clinical and research applications in neurodegeneration. EUFIND comprises 22 European and one US site, including over 50 MRI and dementia experts as well as neuroscientists. Methods: EUFIND combined consensus workshops and data sharing for multisite analysis, focusing on 7 core topics: clinical applications/clinical research, highest resolution anatomy, functional imaging, vascular systems/vascular pathology, iron mapping and neuropathology detection, spectroscopy, and quality assurance. Across these topics, EUFIND considered standard operating procedures, safety, and multivendor harmonization. Results: The clinical and research opportunities and challenges of 7T MRI in each subtopic are set out as a roadmap. Specific MRI sequences for each subtopic were implemented in a pilot study presented in this report. Results show that a large multisite 7T imaging network with highly advanced and harmonized imaging sequences is feasible and may enable future multicentre ultrahigh-field MRI studies and clinical trials. Discussion: The EUFIND network can be a major driver for advancing clinical neuroimaging research using 7T and for identifying use-cases for clinical applications in neurodegeneration. © 2018 The Authors
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| 6. |
- Qiu, C, et al.
(author)
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Cerebral microbleeds, retinopathy, and dementia : the AGES-Reykjavik Study
- 2010
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In: Neurology. - 0028-3878 .- 1526-632X. ; 75:24, s. 2221-8
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To determine whether microvascular damage, indicated by cerebral microbleeds (CMBs) and retinal microvascular signs, is associated with cognitive function and dementia in older persons.METHODS: This is a cross-sectional study of 3,906 participants (mean age 76 years; 58% women) in the AGES-Reykjavik Study (2002-2006). We assessed CMBs on MRI and retinal microvascular signs on digital retinal images. Composite Z scores of memory, processing speed, and executive function were derived from a battery of neurocognitive tests. Dementia and subtypes were diagnosed following international criteria. Regression models were used to relate cognitive Z scores and dementia to CMBs and retinal microvascular signs, adjusting for demographics, cardiovascular factors, and brain ischemic lesions.RESULTS: People with multiple (≥ 2) CMBs had lower Z scores on tests of processing speed (β-coefficient -0.16; 95% confidence interval -0.26 to -0.05) and executive function (-0.14; -0.24 to -0.04); results were strongest for having multiple CMBs located in the deep hemispheric or infratentorial areas. The odds ratio of vascular dementia was 2.32 (95% confidence interval 1.02 to 5.25) for multiple CMBs and 1.95 (1.04 to 3.62) for retinopathy. Having both CMBs and retinopathy, compared to having neither, was significantly associated with markedly slower processing speed (-0.25; -0.37 to -0.12), poorer executive function (-0.19; -0.31 to -0.07), and an increased odds ratio of vascular dementia (3.10; 1.11 to 8.62).CONCLUSION: Having multiple CMBs or concomitant CMBs and retinopathy is associated with a profile of vascular cognitive impairment. These findings suggest that microvascular damage, as indicated by CMBs and retinopathy lesions, has functional consequences in older men and women living in the community.
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| 9. |
- Huybrighs, H. L. F., et al.
(author)
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Energetic Proton Losses Reveal Io's Extended and Longitudinally Asymmetrical Atmosphere
- 2024
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In: Journal of Geophysical Research - Space Physics. - : American Geophysical Union (AGU). - 2169-9380 .- 2169-9402. ; 129:7
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Journal article (peer-reviewed)abstract
- Along the I24, I27, and I31 flybys of Io (1999-2001), the Energetic Particle Detector (EPD) onboard the Galileo spacecraft observed localized regions of energetic protons losses (155-1,250 keV). Using back-tracking particle simulations combined with a prescribed atmospheric distribution and a magnetohydrodynamics (MHD) model of the plasma/atmosphere interaction, we investigate the possible causes of these depletions. We focus on a limited region within two Io radii, which is dominated by Io's SO2 atmosphere. Our results show that charge exchange of protons with the SO2 atmosphere, absorption by the surface and the configuration of the electromagnetic field contribute to the observed proton depletion along the Galileo flybys. In the 155-240 keV energy range, charge exchange is either a major or the dominant loss process, depending on the flyby altitude. In the 540-1,250 keV range, as the charge exchange cross sections are small, the observed decrease of the proton flux is attributed to absorption by the surface and the perturbed electromagnetic fields, which divert the protons away from the detector. From a comparison between the modeled losses and the data we find indications of an extended atmosphere on the day/downstream side of Io, a lack of atmospheric collapse on the night/upstream side as well as a more global extended atmospheric component (>1 Io radius). Our results demonstrate that observations and modeling of proton depletion around the moon constitute an important tool to constrain the electromagnetic field configuration around Io and the radial and longitudinal atmospheric distribution, which is still poorly understood.
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