title: ApoE ε4 Is Associated With Cognition, Brain Integrity, and Atrophy in HIV Over Age 60.
abstract: BACKGROUND
  There are contradicting reports on the associations between Apolipoprotein E4 (ApoE ε4) and brain outcomes in HIV with some evidence that relationships may be greatest in older age groups.
  
  
  METHODS
  We assessed cognition in 76 clinically stable HIV-infected participants over age 60 and genotyped ApoE. Sixty-one of these subjects underwent structural brain magnetic resonance imaging and diffusion tensor imaging.
  
  
  RESULTS
  The median age of the participants was 64 years (range: 60-84) and the median estimated duration of HIV infection was 22 years. Apo ε4 carriers (n = 19) were similar to noncarriers (n = 57) in sex (95% vs. 96% male), and education (16.0 vs. 16.2 years) ApoE ε4 carriers demonstrated greater deficits in cognitive performance in the executive domain (P = 0.045) and had reduced fractional anisotropy and increased mean diffusivity throughout large white matter tracts within the brain compared with noncarriers. Tensor-based morphometry analyses revealed ventricular expansion and atrophy in the posterior corpus callosum, thalamus, and brainstem among HIV-infected ApoE ε4 carriers compared with ε4 noncarriers.
  
  
  CONCLUSIONS
  In this sample of older HIV-infected individuals, having at least 1 ApoE ε4 allele was associated with decreased cognitive performance in the executive functioning domain, reduced brain white matter integrity, and brain atrophy. Brain atrophy was most prominent in the posterior corpus callosum, thalamus, and brainstem. This pattern of cognitive deficit, atrophy, and damage to white matter integrity was similar to that described in HIV, suggesting an exacerbation of HIV-related pathology; although emergence of other age-associated neurodegenerative disorders cannot be excluded.
authors.affiliation: *Department of Neurology, Memory and Aging Center, University of California, San Francisco, CA; †Imaging Genetics Center, Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA; ‡Department of Epidemiology and Biostatistics, University of California, San Francisco, CA; and §Departments of Psychiatry and Neurology, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Wendelken
authors.forename: Neda
authors.initials: N
authors.lastname: Jahanshad
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Rosen
authors.forename: Edgar
authors.initials: E
authors.lastname: Busovaca
authors.forename: Isabel
authors.initials: I
authors.lastname: Allen
authors.forename: Giovanni
authors.initials: G
authors.lastname: Coppola
authors.forename: Collin
authors.initials: C
authors.lastname: Adams
authors.forename: Katherine P
authors.initials: KP
authors.lastname: Rankin
authors.forename: Benedetta
authors.initials: B
authors.lastname: Milanini
authors.forename: Katherine
authors.initials: K
authors.lastname: Clifford
authors.forename: Kevin
authors.initials: K
authors.lastname: Wojta
authors.forename: Talia M
authors.initials: TM
authors.lastname: Nir
authors.forename: Boris A
authors.initials: BA
authors.lastname: Gutman
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
authors.forename: Victor
authors.initials: V
authors.lastname: Valcour
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D001284:Atrophy / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D001927:Brain Diseases / Q000378:metabolism / Q000473:pathology*; D003071:Cognition / Q000502:physiology*; D005786:Gene Expression Regulation; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009483:Neuropsychological Tests
chemical_list: C000612345:ApoE protein, human; D001057:Apolipoproteins E