title: Gray and White Matter Abnormalities in Treated Human Immunodeficiency Virus Disease and Their Relationship to Cognitive Function.
abstract: BACKGROUND
  Long-term comorbidities such as cognitive impairment remain prevalent in otherwise effectively treated people living with human immunodeficiency virus (HIV). We investigate the relationship between cognitive impairment and brain structure in successfully treated patients using multimodal neuroimaging from the Comorbidity in Relation to AIDS (COBRA) cohort.
  
  
  METHODS
  Cognitive function, brain tissue volumes, and white matter microstructure were assessed in 134 HIV-infected 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 4 of the 6 cognitive domains tested (median global T-scores: 50.8 vs 54.2; P < .001). Patients had lower gray 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 gray 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 gray matter volume, and white matter microstructural abnormalities were evident in HIV-infected individuals despite fully suppressive antiretroviral therapy. White matter abnormalities appear to be a particularly important determinant of cognitive dysfunction seen in well-treated HIV-infected individuals.
authors.affiliation: Divisions of Infectious Diseases.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Underwood
authors.affiliation: Brain Sciences, Imperial College London, United Kingdom.
authors.forename: James H
authors.initials: JH
authors.lastname: Cole
authors.affiliation: Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Matthan
authors.initials: M
authors.lastname: Caan
authors.affiliation: Department of Infection and Population Health, University College London, United Kingdom.
authors.forename: Davide
authors.initials: D
authors.lastname: De Francesco
authors.affiliation: Brain Sciences, Imperial College London, United Kingdom.
authors.forename: Robert
authors.initials: R
authors.lastname: Leech
authors.affiliation: Department of Global Health, Academic Medical Center, and Amsterdam Institute for Global Health and Development.
authors.forename: Rosan A
authors.initials: RA
authors.lastname: van Zoest
authors.affiliation: Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Tanja
authors.initials: T
authors.lastname: Su
authors.affiliation: Department of Medical Psychology.
authors.forename: Gert J
authors.initials: GJ
authors.lastname: Geurtsen
authors.affiliation: Department of Medical Psychology.
authors.forename: Ben A
authors.initials: BA
authors.lastname: Schmand
authors.affiliation: Department of Neurology, Academic Medical Center.
authors.forename: Peter
authors.initials: P
authors.lastname: Portegies
authors.affiliation: Public Health Service Amsterdam.
authors.forename: Maria
authors.initials: M
authors.lastname: Prins
authors.affiliation: Department of Global Health, Academic Medical Center, and Amsterdam Institute for Global Health and Development.|HIV Monitoring Foundation.|Department of Internal Medicine, Division of Infectious Diseases, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Ferdinand W N M
authors.initials: FWNM
authors.lastname: Wit
authors.affiliation: Department of Infection and Population Health, University College London, United Kingdom.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Sabin
authors.affiliation: Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Charles
authors.initials: C
authors.lastname: Majoie
authors.affiliation: Department of Global Health, Academic Medical Center, and Amsterdam Institute for Global Health and Development.|HIV Monitoring Foundation.|Department of Internal Medicine, Division of Infectious Diseases, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.affiliation: Divisions of Infectious Diseases.
authors.forename: Alan
authors.initials: A
authors.lastname: Winston
authors.affiliation: Brain Sciences, Imperial College London, United Kingdom.
authors.forename: David J
authors.initials: DJ
authors.lastname: Sharp
mesh_terms: D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000209:etiology / Q000473:pathology; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000473:pathology*; D015658:HIV Infections / Q000150:complications / Q000000981:diagnostic imaging / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D066127:White Matter / Q000000981:diagnostic imaging / Q000473:pathology*
keywords: HIV; cognitive impairment; diffusion tensor imaging; neuroimaging; voxel-based morphometry