title: Independent effects of HIV, aging, and HAART on brain volumetric measures.
abstract: BACKGROUND
  Neurocognitive impairment remains prevalent in HIV-infected (HIV+) individuals despite highly active antiretroviral therapy (HAART). We assessed the impact of HIV, HAART, and aging using structural neuroimaging.
  
  
  METHODS
  Seventy-eight participants [HIV- (n = 26), HIV+ on stable HAART (HIV+/HAART+; n = 26), HIV+ naive to HAART (HIV+/HAART-; n = 26)] completed neuroimaging and neuropsychological testing. A subset of HIV+ subjects (n = 12) performed longitudinal assessments before and after initiating HAART. Neuropsychological tests evaluated memory, psychomotor speed, and executive function, and a composite neuropsychological score was calculated based on normalized performances (neuropsychological summary Z score, NPZ-4). Volumetrics were evaluated for the amygdala, caudate, thalamus, hippocampus, putamen, corpus callosum, and cerebral gray and white matter. A 3-group 1-way analysis of variance assessed differences in neuroimaging and neuropsychological indices. Correlations were examined between NPZ-4 and volumetrics. Exploratory testing using a broken-stick regression model evaluated self-reported duration of HIV infection on brain structure.
  
  
  RESULTS
  HIV+ individuals had significant reductions in brain volumetrics within select subcortical regions (amygdala, caudate, and corpus callosum) compared with HIV- participants. However, HAART did not affect brain structure as regional volumes were similar for HIV+/HAART- and HIV+/HAART+. No association existed between NPZ-4 and volumetrics. HIV and aging were independently associated with volumetric reductions. Exploratory analyses suggest caudate atrophy due to HIV slowly occurs after self-reported seroconversion.
  
  
  CONCLUSIONS
  HIV associated volumetric reductions within the amygdala, caudate, and corpus callosum occurs despite HAART. A gradual decline in caudate volume occurs after self-reported seroconversion. HIV and aging independently increase brain vulnerability. Additional longitudinal structural magnetic resonance imaging studies, especially within older HIV+ participants, are required.
authors.affiliation: Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA. bances@wustl.edu
authors.forename: Beau M
authors.initials: BM
authors.lastname: Ances
authors.forename: Mario
authors.initials: M
authors.lastname: Ortega
authors.forename: Florin
authors.initials: F
authors.lastname: Vaida
authors.forename: Jodi
authors.initials: J
authors.lastname: Heaps
authors.forename: Robert
authors.initials: R
authors.lastname: Paul
mesh_terms: D000328:Adult; D000375:Aging / Q000502:physiology*; D000704:Analysis of Variance; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D001284:Atrophy / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D056344:Executive Function / Q000187:drug effects / Q000502:physiology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D009483:Neuropsychological Tests; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology