eprintid: 1549665 rev_number: 42 eprint_status: archive userid: 608 dir: disk0/01/54/96/65 datestamp: 2017-04-26 13:40:27 lastmod: 2021-12-13 01:28:17 status_changed: 2018-01-22 12:29:36 type: article metadata_visibility: show creators_name: Underwood, J creators_name: Cole, JH creators_name: Caan, M creators_name: De Francesco, D creators_name: Leech, R creators_name: van Zoest, RA creators_name: Su, T creators_name: Geurtsen, GJ creators_name: Schmand, BA creators_name: Portegies, P creators_name: Prins, M creators_name: Wit, FWNM creators_name: Sabin, CA creators_name: Majoie, C creators_name: Reiss, P creators_name: Winston, A creators_name: Sharp, DJ creators_name: Co-morBidity in Relation to Aids (COBRA) Collaboration, . title: Grey and white matter abnormalities in treated HIV-disease and their relationship to cognitive function ispublished: pub divisions: UCL divisions: B02 divisions: D01 divisions: G16 divisions: B04 divisions: C05 divisions: F48 keywords: HIV, cognitive impairment, diffusion tensor imaging, neuroimaging, voxel-based morphometry note: © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. 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. date: 2017-04-06 date_type: published official_url: http://doi.org/10.1093/cid/cix301 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green article_type_text: Journal Article verified: verified_manual elements_id: 1285980 doi: 10.1093/cid/cix301 pii: 3106456 lyricists_name: Cole, James lyricists_name: De Francesco, Davide lyricists_name: Sabin, Caroline lyricists_id: JCOLE07 lyricists_id: DDEFR91 lyricists_id: CASAB15 actors_name: Sabin, Caroline actors_name: Laslett, David actors_id: CASAB15 actors_id: DLASL34 actors_role: owner actors_role: impersonator full_text_status: public publication: Clinical Infectious Diseases volume: 65 number: 3 pagerange: 422-432 event_location: United States issn: 1537-6591 citation: Underwood, J; Cole, JH; Caan, M; De Francesco, D; Leech, R; van Zoest, RA; Su, T; ... Co-morBidity in Relation to Aids (COBRA) Collaboration, .; + view all <#> 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, FWNM; Sabin, CA; Majoie, C; Reiss, P; Winston, A; Sharp, DJ; Co-morBidity in Relation to Aids (COBRA) Collaboration, .; - view fewer <#> (2017) Grey and white matter abnormalities in treated HIV-disease and their relationship to cognitive function. Clinical Infectious Diseases , 65 (3) pp. 422-432. 10.1093/cid/cix301 <https://doi.org/10.1093/cid%2Fcix301>. Green open access document_url: https://discovery-pp.ucl.ac.uk/id/eprint/1549665/1/Sabin_Structural%20brain%20changes%20in%20treated%20HIV%20CID%20resub%20clean.pdf