title: Apolipoprotein-E genotype and human immunodeficiency virus-associated neurocognitive disorder: the modulating effects of older age and disease severity.
abstract: BACKGROUND
  The apolipoprotein-E (APOE) ε4 allele is a risk factor for vascular dementia and Alzheimer's disease. Recent studies are equivocal with regards to whether or not the ε4 allele confers increased risk for the development of human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND), but suggest that age and/or disease severity may be modulating factors. The aim of this study was to assess the interactions and contributions of APOE genotype, age, and HIV disease severity as risk factors for HAND in HIV-infected adults.
  
  
  METHODS
  Participants were 259 HIV-positive individuals who underwent APOE genotyping, a standardized neurological evaluation, a comprehensive neuropsychological evaluation, and laboratory testing.
  
  
  RESULTS
  Older ε4 carriers showed a higher frequency of HAND compared with age-matched non-ε4 carriers. Analysis by discrete neurocognitive domain revealed that advanced age modulated the effect of the ε4 allele, such that older ε4 allele carriers showed reduced executive functioning and information processing speed. Exploratory analyses assessing the relationship between ε4 and disease severity in the overall sample revealed that disease severity modulated the effect of the ε4 allele on cognition. Lower absolute CD4+ cell count among ε4 allele carriers was associated with poorer working memory ability.
  
  
  CONCLUSIONS
  Advancing age and degree of immunosuppression may influence the association between APOE ε4 allele status and HAND. These two factors need to be taken into account in future research.
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, David Geffen School of Medicine ; VA Greater Los Angeles Healthcare System.
authors.forename: Stella E
authors.initials: SE
authors.lastname: Panos
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, David Geffen School of Medicine ; VA Greater Los Angeles Healthcare System.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Hinkin
authors.affiliation: National Neurological AIDS Bank, UCLA Department of Neurology.
authors.forename: Elyse J
authors.initials: EJ
authors.lastname: Singer
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, David Geffen School of Medicine ; VA Greater Los Angeles Healthcare System.
authors.forename: April D
authors.initials: AD
authors.lastname: Thames
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, David Geffen School of Medicine ; VA Greater Los Angeles Healthcare System.
authors.forename: Sapna M
authors.initials: SM
authors.lastname: Patel
authors.affiliation: Departments of Biomathematics and Human Genetics, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, CA.
authors.forename: Janet S
authors.initials: JS
authors.lastname: Sinsheimer
authors.affiliation: Department of Psychiatry, Stanford University, Menlo Park, CA.
authors.forename: A C
authors.initials: AC
authors.lastname: Del Re
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, TX.
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Gelman
authors.affiliation: Departments of Neurology, Neuroscience, and Pathology, The Mount Sinai School of Medicine, New York, NY.
authors.forename: Susan
authors.initials: S
authors.lastname: Morgello
authors.affiliation: Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Moore
authors.affiliation: National Neurological AIDS Bank, UCLA Department of Neurology.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Levine
keywords: aging; apolipoprotein-E; human immunodeficiency virus; neurocognition