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Grey and white matter abnormalities in treated HIV-disease and their relationship to cognitive function.

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Structural brain changes in treated HIV CID resub clean.docxAccepted version111.82 kBMicrosoft WordView/Open
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Title: Grey and white matter abnormalities in treated HIV-disease and their relationship to cognitive function.
Authors: Underwood, J
Cole, JH
Caan, M
De Francesco, D
Leech, R
Van Zoest, RA
Su, T
Geurtsen, GJ
Schmand, BA
Portegies, P
Prins, M
Wit, FW
Sabin, CA
Majoie, C
Reiss, P
Winston, A
Sharp, DJ
Co-morBidity in Relation to Aids (COBRA) Collaboration
Item Type: Journal Article
Abstract: Background: Long-term comorbidities such as cognitive impairment remain prevalent in otherwise effectively treated people-living-with-HIV. We investigate the relationship between cognitive impairment and brain structure in successfully treated patients using multi-modal neuroimaging from the Co-morBidity in Relation to AIDS (COBRA) cohort. Methods: Cognitive function, brain tissue volumes and white matter microstructure were assessed in 134 HIV-positive patients and 79 controls. All patients had suppressed plasma HIV RNA at cohort entry. In addition to comprehensive voxelwise analyses of volumetric and diffusion tensor imaging, we used an unsupervised machine learning approach to combine cognitive, diffusion and volumetric data, taking advantage of the complementary information they provide. Results: Compared to the highly comparable control group, cognitive function was impaired in four out of the six cognitive domains tested (median global T-scores: 50.8 vs. 54.2, p<0.001). Patients had lower grey but not white matter volumes, observed principally in regions where structure generally did not correlate with cognitive function. Widespread abnormalities in white matter microstructure were also seen, including reduced fractional anisotropy with increased mean and radial diffusivity. In contrast to the grey matter, these diffusion abnormalities correlated with cognitive function. Multivariate neuroimaging analysis identified a neuroimaging phenotype associated with poorer cognitive function, HIV-infection and systemic immune activation. Conclusions: Cognitive impairment, lower grey matter volume and white matter microstructural abnormalities were evident in HIV-positive individuals despite fully suppressive antiretroviral therapy. White matter abnormalities appear to be a particularly important determinant of cognitive dysfunction seen in well-treated HIV-positive individuals.
Issue Date: 6-Apr-2017
Date of Acceptance: 29-Mar-2017
URI: http://hdl.handle.net/10044/1/48213
DOI: https://dx.doi.org/10.1093/cid/cix301
ISSN: 1537-6591
Publisher: Oxford University Press (OUP)
Start Page: 422
End Page: 432
Journal / Book Title: Clinical Infectious Diseases
Volume: 65
Issue: 3
Copyright Statement: © 2017 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. This is a pre-copy-editing, author-produced version of an article accepted for publication in Clinical Infectious Diseases following peer review. The definitive publisher-authenticated version Jonathan Underwood, James H. Cole, Matthan Caan, Davide De Francesco, Robert Leech, Rosan A. van Zoest, Tanja Su, Gert J. Geurtsen, Ben A. Schmand, Peter Portegies, Maria Prins, Ferdinand W. N. M. Wit, Caroline A. Sabin, Charles Majoie, Peter Reiss, Alan Winston, David J. Sharp, for the Comorbidity in Relation to AIDS (COBRA) Collaboration; Gray and White Matter Abnormalities in Treated Human Immunodeficiency Virus Disease and Their Relationship to Cognitive Function. Clin Infect Dis 2017 cix301. doi: 10.1093/cid/cix301 is available online at: https://dx.doi.org/10.1093/cid/cix301
Sponsor/Funder: Commission of the European Communities
National Institute for Health Research
Imperial College Healthcare NHS Trust- BRC Funding
Funder's Grant Number: 305522
NIHR-RP-011-048
RDC04 79560
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
Infectious Diseases
Microbiology
HIV
cognitive impairment
neuroimaging
diffusion tensor imaging
voxel-based morphometry
NEUROCOGNITIVE DISORDERS
HIV-INFECTION
ANTIRETROVIRAL THERAPY
IMPAIRMENT
BRAIN
INDIVIDUALS
COHORT
REGISTRATION
PREVALENCE
INTEGRITY
Comorbidity in Relation to AIDS (COBRA) Collaboration
06 Biological Sciences
11 Medical And Health Sciences
Publication Status: Published
Appears in Collections:Department of Medicine (up to 2019)