title: Increased brain-predicted aging in treated HIV disease.
abstract: OBJECTIVE
  To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters.
  
  
  METHODS
  A large sample of virologically suppressed HIV-positive adults (n = 162, age 45-82 years) and highly comparable HIV-negative controls (n = 105) were recruited as part of the Comorbidity in Relation to AIDS (COBRA) collaboration. Using T1-weighted MRI scans, a machine-learning model of healthy brain aging was defined in an independent cohort (n = 2,001, aged 18-90 years). Neuroimaging data from HIV-positive and HIV-negative individuals were then used to estimate brain-predicted age; then brain-predicted age difference (brain-PAD = brain-predicted brain age - chronological age) scores were calculated. Neuropsychological and clinical assessments were also carried out.
  
  
  RESULTS
  HIV-positive individuals had greater brain-PAD score (mean ± SD 2.15 ± 7.79 years) compared to HIV-negative individuals (-0.87 ± 8.40 years;b= 3.48,p< 0.01). Increased brain-PAD score was associated with decreased performance in multiple cognitive domains (information processing speed, executive function, memory) and general cognitive performance across all participants. Brain-PAD score was not associated with age, duration of HIV infection, or other HIV-related measures.
  
  
  CONCLUSIONS
  Increased apparent brain aging, predicted using neuroimaging, was observed in HIV-positive adults, despite effective viral suppression. Furthermore, the magnitude of increased apparent brain aging related to cognitive deficits. However, predicted brain age difference did not correlate with chronological age or duration of HIV infection, suggesting that HIV disease may accentuate rather than accelerate brain aging.
authors.affiliation: From the Computational, Cognitive & Clinical Neuroimaging Laboratory, Division of Brain Sciences, Department of Medicine (J.H.C., R.L., D.J.S.), and Division of Infectious Diseases (J.U., A.W.), Imperial College London, UK; Departments of Radiology (M.W.A.C., C.B.L.M.M.), Global Health, Amsterdam Institute for Global Health and Development (AIGHD) (R.A.v.Z., F.W.N.M.W., P.R.), Neurology (P.P., B.A.S.), and Medical Psychology (G.J.G., B.A.S.), Academic Medical Center, Amsterdam, the Netherlands; Department of Infection & Population Health (D.D.F., C.A.S.), University College London, UK; Dutch HIV Monitoring Foundation (F.W.N.M.W., P.R.); Department of Neurology (P.P.), OLVG Hospital; Public Health Service of Amsterdam (M.F.S.v.d.L.), the Netherlands; and Alma Mater Studiorum (C.F.), University of Bologna, Italy. james.cole@imperial.ac.uk.
authors.forename: James H
authors.initials: JH
authors.lastname: Cole
authors.affiliation: From the Computational, Cognitive & Clinical Neuroimaging Laboratory, Division of Brain Sciences, Department of Medicine (J.H.C., R.L., D.J.S.), and Division of Infectious Diseases (J.U., A.W.), Imperial College London, UK; Departments of Radiology (M.W.A.C., C.B.L.M.M.), Global Health, Amsterdam Institute for Global Health and Development (AIGHD) (R.A.v.Z., F.W.N.M.W., P.R.), Neurology (P.P., B.A.S.), and Medical Psychology (G.J.G., B.A.S.), Academic Medical Center, Amsterdam, the Netherlands; Department of Infection & Population Health (D.D.F., C.A.S.), University College London, UK; Dutch HIV Monitoring Foundation (F.W.N.M.W., P.R.); Department of Neurology (P.P.), OLVG Hospital; Public Health Service of Amsterdam (M.F.S.v.d.L.), the Netherlands; and Alma Mater Studiorum (C.F.), University of Bologna, Italy.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Underwood
authors.affiliation: From the Computational, Cognitive & Clinical Neuroimaging Laboratory, Division of Brain Sciences, Department of Medicine (J.H.C., R.L., D.J.S.), and Division of Infectious Diseases (J.U., A.W.), Imperial College London, UK; Departments of Radiology (M.W.A.C., C.B.L.M.M.), Global Health, Amsterdam Institute for Global Health and Development (AIGHD) (R.A.v.Z., F.W.N.M.W., P.R.), Neurology (P.P., B.A.S.), and Medical Psychology (G.J.G., B.A.S.), Academic Medical Center, Amsterdam, the Netherlands; Department of Infection & Population Health (D.D.F., C.A.S.), University College London, UK; Dutch HIV Monitoring Foundation (F.W.N.M.W., P.R.); Department of Neurology (P.P.), OLVG Hospital; Public Health Service of Amsterdam (M.F.S.v.d.L.), the Netherlands; and Alma Mater Studiorum (C.F.), University of Bologna, Italy.
authors.forename: Matthan W A
authors.initials: MW
authors.lastname: Caan
authors.affiliation: From the Computational, Cognitive & Clinical Neuroimaging Laboratory, Division of Brain Sciences, Department of Medicine (J.H.C., R.L., D.J.S.), and Division of Infectious Diseases (J.U., A.W.), Imperial College London, UK; Departments of Radiology (M.W.A.C., C.B.L.M.M.), Global Health, Amsterdam Institute for Global Health and Development (AIGHD) (R.A.v.Z., F.W.N.M.W., P.R.), Neurology (P.P., B.A.S.), and Medical Psychology (G.J.G., B.A.S.), Academic Medical Center, Amsterdam, the Netherlands; Department of Infection & Population Health (D.D.F., C.A.S.), University College London, UK; Dutch HIV Monitoring Foundation (F.W.N.M.W., P.R.); Department of Neurology (P.P.), OLVG Hospital; Public Health Service of Amsterdam (M.F.S.v.d.L.), the Netherlands; and Alma Mater Studiorum (C.F.), University of Bologna, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: De Francesco
authors.affiliation: From the Computational, Cognitive & Clinical Neuroimaging Laboratory, Division of Brain Sciences, Department of Medicine (J.H.C., R.L., D.J.S.), and Division of Infectious Diseases (J.U., A.W.), Imperial College London, UK; Departments of Radiology (M.W.A.C., C.B.L.M.M.), Global Health, Amsterdam Institute for Global Health and Development (AIGHD) (R.A.v.Z., F.W.N.M.W., P.R.), Neurology (P.P., B.A.S.), and Medical Psychology (G.J.G., B.A.S.), Academic Medical Center, Amsterdam, the Netherlands; Department of Infection & Population Health (D.D.F., C.A.S.), University College London, UK; Dutch HIV Monitoring Foundation (F.W.N.M.W., P.R.); Department of Neurology (P.P.), OLVG Hospital; Public Health Service of Amsterdam (M.F.S.v.d.L.), the Netherlands; and Alma Mater Studiorum (C.F.), University of Bologna, Italy.
authors.forename: Rosan A
authors.initials: RA
authors.lastname: van Zoest
authors.affiliation: From the Computational, Cognitive & Clinical Neuroimaging Laboratory, Division of Brain Sciences, Department of Medicine (J.H.C., R.L., D.J.S.), and Division of Infectious Diseases (J.U., A.W.), Imperial College London, UK; Departments of Radiology (M.W.A.C., C.B.L.M.M.), Global Health, Amsterdam Institute for Global Health and Development (AIGHD) (R.A.v.Z., F.W.N.M.W., P.R.), Neurology (P.P., B.A.S.), and Medical Psychology (G.J.G., B.A.S.), Academic Medical Center, Amsterdam, the Netherlands; Department of Infection & Population Health (D.D.F., C.A.S.), University College London, UK; Dutch HIV Monitoring Foundation (F.W.N.M.W., P.R.); Department of Neurology (P.P.), OLVG Hospital; Public Health Service of Amsterdam (M.F.S.v.d.L.), the Netherlands; and Alma Mater Studiorum (C.F.), University of Bologna, Italy.
authors.forename: Robert
authors.initials: R
authors.lastname: Leech
authors.affiliation: From the Computational, Cognitive & Clinical Neuroimaging Laboratory, Division of Brain Sciences, Department of Medicine (J.H.C., R.L., D.J.S.), and Division of Infectious Diseases (J.U., A.W.), Imperial College London, UK; Departments of Radiology (M.W.A.C., C.B.L.M.M.), Global Health, Amsterdam Institute for Global Health and Development (AIGHD) (R.A.v.Z., F.W.N.M.W., P.R.), Neurology (P.P., B.A.S.), and Medical Psychology (G.J.G., B.A.S.), Academic Medical Center, Amsterdam, the Netherlands; Department of Infection & Population Health (D.D.F., C.A.S.), University College London, UK; Dutch HIV Monitoring Foundation (F.W.N.M.W., P.R.); Department of Neurology (P.P.), OLVG Hospital; Public Health Service of Amsterdam (M.F.S.v.d.L.), the Netherlands; and Alma Mater Studiorum (C.F.), University of Bologna, Italy.
authors.forename: Ferdinand W N M
authors.initials: FW
authors.lastname: Wit
authors.affiliation: From the Computational, Cognitive & Clinical Neuroimaging Laboratory, Division of Brain Sciences, Department of Medicine (J.H.C., R.L., D.J.S.), and Division of Infectious Diseases (J.U., A.W.), Imperial College London, UK; Departments of Radiology (M.W.A.C., C.B.L.M.M.), Global Health, Amsterdam Institute for Global Health and Development (AIGHD) (R.A.v.Z., F.W.N.M.W., P.R.), Neurology (P.P., B.A.S.), and Medical Psychology (G.J.G., B.A.S.), Academic Medical Center, Amsterdam, the Netherlands; Department of Infection & Population Health (D.D.F., C.A.S.), University College London, UK; Dutch HIV Monitoring Foundation (F.W.N.M.W., P.R.); Department of Neurology (P.P.), OLVG Hospital; Public Health Service of Amsterdam (M.F.S.v.d.L.), the Netherlands; and Alma Mater Studiorum (C.F.), University of Bologna, Italy.
authors.forename: Peter
authors.initials: P
authors.lastname: Portegies
authors.affiliation: From the Computational, Cognitive & Clinical Neuroimaging Laboratory, Division of Brain Sciences, Department of Medicine (J.H.C., R.L., D.J.S.), and Division of Infectious Diseases (J.U., A.W.), Imperial College London, UK; Departments of Radiology (M.W.A.C., C.B.L.M.M.), Global Health, Amsterdam Institute for Global Health and Development (AIGHD) (R.A.v.Z., F.W.N.M.W., P.R.), Neurology (P.P., B.A.S.), and Medical Psychology (G.J.G., B.A.S.), Academic Medical Center, Amsterdam, the Netherlands; Department of Infection & Population Health (D.D.F., C.A.S.), University College London, UK; Dutch HIV Monitoring Foundation (F.W.N.M.W., P.R.); Department of Neurology (P.P.), OLVG Hospital; Public Health Service of Amsterdam (M.F.S.v.d.L.), the Netherlands; and Alma Mater Studiorum (C.F.), University of Bologna, Italy.
authors.forename: Gert J
authors.initials: GJ
authors.lastname: Geurtsen
authors.affiliation: From the Computational, Cognitive & Clinical Neuroimaging Laboratory, Division of Brain Sciences, Department of Medicine (J.H.C., R.L., D.J.S.), and Division of Infectious Diseases (J.U., A.W.), Imperial College London, UK; Departments of Radiology (M.W.A.C., C.B.L.M.M.), Global Health, Amsterdam Institute for Global Health and Development (AIGHD) (R.A.v.Z., F.W.N.M.W., P.R.), Neurology (P.P., B.A.S.), and Medical Psychology (G.J.G., B.A.S.), Academic Medical Center, Amsterdam, the Netherlands; Department of Infection & Population Health (D.D.F., C.A.S.), University College London, UK; Dutch HIV Monitoring Foundation (F.W.N.M.W., P.R.); Department of Neurology (P.P.), OLVG Hospital; Public Health Service of Amsterdam (M.F.S.v.d.L.), the Netherlands; and Alma Mater Studiorum (C.F.), University of Bologna, Italy.
authors.forename: Ben A
authors.initials: BA
authors.lastname: Schmand
authors.affiliation: From the Computational, Cognitive & Clinical Neuroimaging Laboratory, Division of Brain Sciences, Department of Medicine (J.H.C., R.L., D.J.S.), and Division of Infectious Diseases (J.U., A.W.), Imperial College London, UK; Departments of Radiology (M.W.A.C., C.B.L.M.M.), Global Health, Amsterdam Institute for Global Health and Development (AIGHD) (R.A.v.Z., F.W.N.M.W., P.R.), Neurology (P.P., B.A.S.), and Medical Psychology (G.J.G., B.A.S.), Academic Medical Center, Amsterdam, the Netherlands; Department of Infection & Population Health (D.D.F., C.A.S.), University College London, UK; Dutch HIV Monitoring Foundation (F.W.N.M.W., P.R.); Department of Neurology (P.P.), OLVG Hospital; Public Health Service of Amsterdam (M.F.S.v.d.L.), the Netherlands; and Alma Mater Studiorum (C.F.), University of Bologna, Italy.
authors.forename: Maarten F
authors.initials: MF
authors.lastname: Schim van der Loeff
authors.affiliation: From the Computational, Cognitive & Clinical Neuroimaging Laboratory, Division of Brain Sciences, Department of Medicine (J.H.C., R.L., D.J.S.), and Division of Infectious Diseases (J.U., A.W.), Imperial College London, UK; Departments of Radiology (M.W.A.C., C.B.L.M.M.), Global Health, Amsterdam Institute for Global Health and Development (AIGHD) (R.A.v.Z., F.W.N.M.W., P.R.), Neurology (P.P., B.A.S.), and Medical Psychology (G.J.G., B.A.S.), Academic Medical Center, Amsterdam, the Netherlands; Department of Infection & Population Health (D.D.F., C.A.S.), University College London, UK; Dutch HIV Monitoring Foundation (F.W.N.M.W., P.R.); Department of Neurology (P.P.), OLVG Hospital; Public Health Service of Amsterdam (M.F.S.v.d.L.), the Netherlands; and Alma Mater Studiorum (C.F.), University of Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
authors.affiliation: From the Computational, Cognitive & Clinical Neuroimaging Laboratory, Division of Brain Sciences, Department of Medicine (J.H.C., R.L., D.J.S.), and Division of Infectious Diseases (J.U., A.W.), Imperial College London, UK; Departments of Radiology (M.W.A.C., C.B.L.M.M.), Global Health, Amsterdam Institute for Global Health and Development (AIGHD) (R.A.v.Z., F.W.N.M.W., P.R.), Neurology (P.P., B.A.S.), and Medical Psychology (G.J.G., B.A.S.), Academic Medical Center, Amsterdam, the Netherlands; Department of Infection & Population Health (D.D.F., C.A.S.), University College London, UK; Dutch HIV Monitoring Foundation (F.W.N.M.W., P.R.); Department of Neurology (P.P.), OLVG Hospital; Public Health Service of Amsterdam (M.F.S.v.d.L.), the Netherlands; and Alma Mater Studiorum (C.F.), University of Bologna, Italy.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Sabin
authors.affiliation: From the Computational, Cognitive & Clinical Neuroimaging Laboratory, Division of Brain Sciences, Department of Medicine (J.H.C., R.L., D.J.S.), and Division of Infectious Diseases (J.U., A.W.), Imperial College London, UK; Departments of Radiology (M.W.A.C., C.B.L.M.M.), Global Health, Amsterdam Institute for Global Health and Development (AIGHD) (R.A.v.Z., F.W.N.M.W., P.R.), Neurology (P.P., B.A.S.), and Medical Psychology (G.J.G., B.A.S.), Academic Medical Center, Amsterdam, the Netherlands; Department of Infection & Population Health (D.D.F., C.A.S.), University College London, UK; Dutch HIV Monitoring Foundation (F.W.N.M.W., P.R.); Department of Neurology (P.P.), OLVG Hospital; Public Health Service of Amsterdam (M.F.S.v.d.L.), the Netherlands; and Alma Mater Studiorum (C.F.), University of Bologna, Italy.
authors.forename: Charles B L M
authors.initials: CB
authors.lastname: Majoie
authors.affiliation: From the Computational, Cognitive & Clinical Neuroimaging Laboratory, Division of Brain Sciences, Department of Medicine (J.H.C., R.L., D.J.S.), and Division of Infectious Diseases (J.U., A.W.), Imperial College London, UK; Departments of Radiology (M.W.A.C., C.B.L.M.M.), Global Health, Amsterdam Institute for Global Health and Development (AIGHD) (R.A.v.Z., F.W.N.M.W., P.R.), Neurology (P.P., B.A.S.), and Medical Psychology (G.J.G., B.A.S.), Academic Medical Center, Amsterdam, the Netherlands; Department of Infection & Population Health (D.D.F., C.A.S.), University College London, UK; Dutch HIV Monitoring Foundation (F.W.N.M.W., P.R.); Department of Neurology (P.P.), OLVG Hospital; Public Health Service of Amsterdam (M.F.S.v.d.L.), the Netherlands; and Alma Mater Studiorum (C.F.), University of Bologna, Italy.
authors.forename: Alan
authors.initials: A
authors.lastname: Winston
authors.affiliation: From the Computational, Cognitive & Clinical Neuroimaging Laboratory, Division of Brain Sciences, Department of Medicine (J.H.C., R.L., D.J.S.), and Division of Infectious Diseases (J.U., A.W.), Imperial College London, UK; Departments of Radiology (M.W.A.C., C.B.L.M.M.), Global Health, Amsterdam Institute for Global Health and Development (AIGHD) (R.A.v.Z., F.W.N.M.W., P.R.), Neurology (P.P., B.A.S.), and Medical Psychology (G.J.G., B.A.S.), Academic Medical Center, Amsterdam, the Netherlands; Department of Infection & Population Health (D.D.F., C.A.S.), University College London, UK; Dutch HIV Monitoring Foundation (F.W.N.M.W., P.R.); Department of Neurology (P.P.), OLVG Hospital; Public Health Service of Amsterdam (M.F.S.v.d.L.), the Netherlands; and Alma Mater Studiorum (C.F.), University of Bologna, Italy.
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.affiliation: From the Computational, Cognitive & Clinical Neuroimaging Laboratory, Division of Brain Sciences, Department of Medicine (J.H.C., R.L., D.J.S.), and Division of Infectious Diseases (J.U., A.W.), Imperial College London, UK; Departments of Radiology (M.W.A.C., C.B.L.M.M.), Global Health, Amsterdam Institute for Global Health and Development (AIGHD) (R.A.v.Z., F.W.N.M.W., P.R.), Neurology (P.P., B.A.S.), and Medical Psychology (G.J.G., B.A.S.), Academic Medical Center, Amsterdam, the Netherlands; Department of Infection & Population Health (D.D.F., C.A.S.), University College London, UK; Dutch HIV Monitoring Foundation (F.W.N.M.W., P.R.); Department of Neurology (P.P.), OLVG Hospital; Public Health Service of Amsterdam (M.F.S.v.d.L.), the Netherlands; and Alma Mater Studiorum (C.F.), University of Bologna, Italy.
authors.forename: David J
authors.initials: DJ
authors.lastname: Sharp
mesh_terms: D000375:Aging; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology* / Q000821:virology; D003072:Cognition Disorders / Q000209:etiology*; D005260:Female; D006678:HIV / Q000235:genetics; D015658:HIV Infections / Q000097:blood / Q000150:complications* / Q000000981:diagnostic imaging; D006801:Humans; D021621:Imaging, Three-Dimensional; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D012313:RNA / Q000302:isolation & purification
chemical_list: D012313:RNA