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Neurobehav HIV Med. 2013;5:11-22. doi: 10.2147/NBHIV.S39573. Epub 2013 Jun 19.

Apolipoprotein-E genotype and human immunodeficiency virus-associated neurocognitive disorder: the modulating effects of older age and disease severity.

Neurobehavioral HIV medicine

Stella E Panos, Charles H Hinkin, Elyse J Singer, April D Thames, Sapna M Patel, Janet S Sinsheimer, A C Del Re, Benjamin B Gelman, Susan Morgello, David J Moore, Andrew J Levine

Affiliations

  1. Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, David Geffen School of Medicine ; VA Greater Los Angeles Healthcare System.
  2. National Neurological AIDS Bank, UCLA Department of Neurology.
  3. Departments of Biomathematics and Human Genetics, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, CA.
  4. Department of Psychiatry, Stanford University, Menlo Park, CA.
  5. Department of Pathology, University of Texas Medical Branch, Galveston, TX.
  6. Departments of Neurology, Neuroscience, and Pathology, The Mount Sinai School of Medicine, New York, NY.
  7. Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA, USA.

PMID: 26617462 PMCID: PMC4659385 DOI: 10.2147/NBHIV.S39573

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.

CONCLUSION: 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.

Keywords: aging; apolipoprotein-E; human immunodeficiency virus; neurocognition

References

  1. Psychopharmacology (Berl). 2008 Nov;201(1):125-35 - PubMed
  2. J Neural Transm (Vienna). 2012 Mar;119(3):387-94 - PubMed
  3. JAMA. 1997 Oct 22-29;278(16):1349-56 - PubMed
  4. J Exp Psychol. 1948 Aug;38(4):404-11 - PubMed
  5. Brain. 2005 Nov;128(Pt 11):2556-61 - PubMed
  6. Genet Epidemiol. 1994;11(4):375-84 - PubMed
  7. N Engl J Med. 2009 Jul 16;361(3):255-63 - PubMed
  8. Int J Alzheimers Dis. 2011 Feb 24;2011:726197 - PubMed
  9. Am J Geriatr Psychiatry. 2009 Apr;17(4):281-90 - PubMed
  10. Nat Med. 1998 Oct;4(10):1182-4 - PubMed
  11. Neurobiol Aging. 2010 Oct;31(10):1831-3 - PubMed
  12. Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):E87 - PubMed
  13. Sex Transm Infect. 2008 Dec;84(7):516-7 - PubMed
  14. Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):E66; author reply E67-8 - PubMed
  15. Neurology. 2004 Sep 14;63(5):822-7 - PubMed
  16. J Neuroimmune Pharmacol. 2011 Sep;6(3):389-98 - PubMed
  17. Rejuvenation Res. 2013 Feb;16(1):28-34 - PubMed
  18. BMC Med Genet. 2011 Mar 24;12:43 - PubMed
  19. Clin Neuropsychol. 1999 Aug;13(3):348-58 - PubMed
  20. Neurosci Lett. 2000 Nov 24;294(3):179-81 - PubMed
  21. Neurology. 2002 Dec 24;59(12):1944-50 - PubMed
  22. Exp Eye Res. 2007 May;84(5):801-11 - PubMed
  23. Dement Geriatr Cogn Disord. 2010;29(3):248-53 - PubMed
  24. Neurology. 1991 Jun;41(6):778-85 - PubMed
  25. J Neuroimmunol. 2004 Dec;157(1-2):197-202 - PubMed
  26. Am J Psychiatry. 1996 Sep;153(9):1195-201 - PubMed
  27. J Neurovirol. 2002 Dec;8 Suppl 2:115-21 - PubMed
  28. J Neurovirol. 2010 Oct;16(5):377-83 - PubMed
  29. Alzheimer Dis Assoc Disord. 2008 Jan-Mar;22(1):6-20 - PubMed
  30. Pediatr Res. 2003 Dec;54(6):819-25 - PubMed
  31. Aging Cell. 2011 Jun;10(3):533-41 - PubMed
  32. Mol Nutr Food Res. 2008 Jan;52(1):131-45 - PubMed
  33. Lipids Health Dis. 2010 Jan 28;9:8 - PubMed
  34. Neuropathol Appl Neurobiol. 2001 Aug;27(4):326-35 - PubMed
  35. Proc Natl Acad Sci U S A. 2008 Jun 24;105(25):8718-23 - PubMed
  36. Alzheimer Dis Assoc Disord. 2006 Jul-Sep;20(3 Suppl 2):S69-74 - PubMed
  37. Lancet. 1997 Oct 11;350(9084):1069-71 - PubMed
  38. Neuroimage. 2011 Oct 15;58(4):1017-27 - PubMed
  39. HIV Med. 2008 Oct;9(8):677-80 - PubMed
  40. Ageing Res Rev. 2002 Jun;1(3):345-65 - PubMed
  41. AIDS. 2005 Mar 24;19(6):634-5 - PubMed
  42. Neurology. 2010 Dec 7;75(23):2087-96 - PubMed
  43. J Clin Exp Neuropsychol. 1997 Aug;19(4):473-83 - PubMed
  44. AIDS. 2010 Jun 19;24(10):1471-9 - PubMed
  45. J Neurovirol. 2010 Mar;16(2):115-24 - PubMed
  46. Neurobiol Aging. 2009 Sep;30(9):1350-60 - PubMed
  47. PLoS One. 2010 Apr 02;5(4):e10022 - PubMed
  48. J Acquir Immune Defic Syndr. 1993 May;6(5):503-11 - PubMed
  49. Arch Neurol. 2000 Nov;57(11):1561-5 - PubMed
  50. Oncology. 2004;66(2):79-93 - PubMed
  51. Neurology. 2007 Oct 30;69(18):1789-99 - PubMed
  52. JAMA. 1998 Nov 4;280(17):1497-503 - PubMed
  53. J Clin Exp Neuropsychol. 2012;34(1):78-91 - PubMed

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