Journal of NeuroVirology

, Volume 18, Issue 4, pp 256–263

Impact of HIV and aging on neuropsychological function

Article

Abstract

Cognitive efficiency decreases with age, and advancing age is the leading risk factor for most neurodegenerative disorders that result in dementia. In HIV infection, risk for cognitive impairment is consistently linked to advancing chronological age. As the HIV epidemic enters its fourth decade in the USA, extended life expectancy will likely result in an increased prevalence of cognitive disorders by virtue of these factors. However, it is less clear if HIV potentiates or accelerates the risk for cognitive impairment given that most reports are mixed or demonstrate only a small interaction effect. More critically, it is unclear if HIV will modulate the neuropathology associated with non-HIV cognitive disorders in a manner that will increase risk for diseases such as cerebrovascular and Alzheimer’s disease. In the coming years, with increasing numbers of HIV+ patients entering their 60s and 70s, background risk for neurodegenerative disorders will be sufficiently high as to inform this issue on clinical grounds. This review summarizes knowledge of cognition in HIV as it relates to age and presents some emerging controversies.

Keywords

HIV Dementia Cognition Aging 

References

  1. Alisky JM (2007) The coming problem of HIV-associated Alzheimer’s disease. Med Hypotheses 69:1140–1143PubMedCrossRefGoogle Scholar
  2. Ances BM, Ellis RJ (2007) Dementia and neurocognitive disorders due to HIV-1 infection. Semin Neurol 27:86–92PubMedCrossRefGoogle Scholar
  3. Anthony IC, Ramage SN, Carnie FW, Simmonds P, Bell JE (2006) Accelerated Tau deposition in the brains of individuals infected with human immunodeficiency virus-1 before and after the advent of highly active anti-retroviral therapy. Acta Neuropathol 111:529–538PubMedCrossRefGoogle Scholar
  4. Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M, Clifford DB, Cinque P, Epstein LG, Goodkin K, Gisslen M, Grant I, Heaton RK, Joseph J, Marder K, Marra CM, McArthur JC, Nunn M, Price RW, Pulliam L, Robertson KR, Sacktor N, Valcour V, Wojna VE (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69:1789–1799PubMedCrossRefGoogle Scholar
  5. Becker JT, Lopez OL, Dew MA, Aizenstein HJ (2004) Prevalence of cognitive disorders differs as a function of age in HIV virus infection. AIDS 18(Suppl 1):S11–S18PubMedGoogle Scholar
  6. Becker JT, Kingsley L, Mullen J, Cohen B, Martin E, Miller EN, Ragin A, Sacktor N, Selnes OA, Visscher BR (2009) Vascular risk factors, HIV serostatus, and cognitive dysfunction in gay and bisexual men. Neurology 73:1292–1299PubMedCrossRefGoogle Scholar
  7. Bhaskaran K, Mussini C, Antinori A, Walker AS, Dorrucci M, Sabin C, Phillips A, Porter K (2008) Changes in the incidence and predictors of human immunodeficiency virus-associated dementia in the era of highly active antiretroviral therapy. Ann Neurol 63:213–221PubMedCrossRefGoogle Scholar
  8. Blackstone K, Moore DJ, Heaton RK, Franklin DR Jr, Woods SP, Clifford DB, Collier AC, Marra CM, Gelman BB, McArthur JC, Morgello S, Simpson DM, Rivera-Mindt M, Deutsch R, Ellis RJ, Hampton Atkinson J, Grant I (2012) Diagnosing symptomatic HIV-associated neurocognitive disorders: self-report versus performance-based assessment of everyday functioning. J Int Neuropsychol Soc 18:79–88PubMedCrossRefGoogle Scholar
  9. Castilla J, Sobrino P, De La Fuente L, Noguer I, Guerra L, Parras F (2002) Late diagnosis of HIV infection in the era of highly active antiretroviral therapy: consequences for AIDS incidence. AIDS 16:1945–1951PubMedCrossRefGoogle Scholar
  10. CDC (2009) Centers for Disease Control and Prevention. HIV Surveillance Report, vol. 21. http://www.cdc.gov/hiv/topics/surveillance/resources/reports/#surveillance; Published February 2011. Accessed Aug 2011
  11. Cherner M, Ellis RJ, Lazzaretto D, Young C, Mindt MR, Atkinson JH, Grant I, Heaton RK (2004) Effects of HIV-1 infection and aging on neurobehavioral functioning: preliminary findings. AIDS 18(Suppl 1):S27–S34PubMedGoogle Scholar
  12. Chiesi A, Vella S, Dally LG, Pedersen C, Danner S, Johnson AM, Schwander S, Goebel FD, Glauser M, Antunes F et al (1996) Epidemiology of AIDS dementia complex in Europe. AIDS in Europe Study Group. J Acquir Immune Defic Syndr Hum Retrovirol 11:39–44PubMedCrossRefGoogle Scholar
  13. Cysique LA, Maruff P, Bain MP, Wright E, Brew BJ (2011) HIV and age do not substantially interact in HIV-associated neurocognitive impairment. J Neuropsychiatry Clin Neurosci 23:83–89PubMedCrossRefGoogle Scholar
  14. Ferro S, Salit IE (1992) HIV infection in patients over 55 years of age. J Acquir Immune Defic Syndr 5:348–353PubMedGoogle Scholar
  15. Gandhi NS, Skolasky RL, Peters KB, Moxley RTT, Creighton J, Roosa HV, Selnes OA, McArthur J, Sacktor N (2011) A comparison of performance-based measures of function in HIV-associated neurocognitive disorders. J Neurovirol 17:159–165PubMedCrossRefGoogle Scholar
  16. Goodkin K, Wilkie FL, Concha M, Hinkin CH, Symes S, Baldewicz TT, Asthana D, Fujimura RK, Lee D, van Zuilen MH, Khamis I, Shapshak P, Eisdorfer C (2001) Aging and neuro-AIDS conditions and the changing spectrum of HIV-1-associated morbidity and mortality. J Clin Epidemiol 54(Suppl 1):S35–S43PubMedCrossRefGoogle Scholar
  17. Green DA, Masliah E, Vinters HV, Beizai P, Moore DJ, Achim CL (2005) Brain deposition of beta-amyloid is a common pathologic feature in HIV positive patients. AIDS 19:407–411PubMedCrossRefGoogle Scholar
  18. Grov C, Golub SA, Parsons JT, Brennan M, Karpiak SE (2010) Loneliness and HIV-related stigma explain depression among older HIV-positive adults. AIDS Care 22:630–639PubMedCrossRefGoogle Scholar
  19. Hardy J, Hinkin C, Satz P, Stenquist P, van Gorp W, Moore L (1999) Age differences and neurocognitive performance in HIV-infected adults. N Z J Psychol 28:94–101Google Scholar
  20. Heaton RK, Marcotte TD, Mindt MR, Sadek J, Moore DJ, Bentley H, McCutchan JA, Reicks C, Grant I (2004) The impact of HIV-associated neuropsychological impairment on everyday functioning. J Int Neuropsychol Soc 10:317–331PubMedCrossRefGoogle Scholar
  21. Heaton RK, Clifford DB, Franklin DR Jr, Woods SP, Ake C, Vaida F, Ellis RJ, Letendre SL, Marcotte TD, Atkinson JH, Rivera-Mindt M, Vigil OR, Taylor MJ, Collier AC, Marra CM, Gelman BB, McArthur JC, Morgello S, Simpson DM, McCutchan JA, Abramson I, Gamst A, Fennema-Notestine C, Jernigan TL, Wong J, Grant I (2010) HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology 75:2087–2096PubMedCrossRefGoogle Scholar
  22. Heaton RK, Franklin DR, Ellis RJ, McCutchan JA, Letendre SL, Leblanc S, Corkran SH, Duarte NA, Clifford DB, Woods SP, Collier AC, Marra CM, Morgello S, Mindt MR, Taylor MJ, Marcotte TD, Atkinson JH, Wolfson T, Gelman BB, McArthur JC, Simpson DM, Abramson I, Gamst A, Fennema-Notestine C, Jernigan TL, Wong J, Grant I (2011) HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirol 17:3–16PubMedCrossRefGoogle Scholar
  23. Janssen RS, Nwanyanwu OC, Selik RM, Stehr-Green JK (1992) Epidemiology of human immunodeficiency virus encephalopathy in the United States. Neurology 42:1472–1476PubMedCrossRefGoogle Scholar
  24. Kissel EC, Pukay-Martin ND, Bornstein RA (2005) The relationship between age and cognitive function in HIV-infected men. J Neuropsychiatry Clin Neurosci 17:180–184PubMedCrossRefGoogle Scholar
  25. Linsk NL (2000) HIV among older adults: age-specific issues in prevention and treatment. AIDS Read 10:430–440PubMedGoogle Scholar
  26. Mamary EM, Bahrs D, Martinez S (2002) Cigarette smoking and the desire to quit among individuals living with HIV. AIDS Patient Care STDS 16:39–42PubMedCrossRefGoogle Scholar
  27. Manfredi R (2004) HIV infection and advanced age emerging epidemiological, clinical, and management issues. Ageing Res Rev 3:31–54PubMedCrossRefGoogle Scholar
  28. McArthur JC, Hoover DR, Bacellar H, Miller EN, Cohen BA, Becker JT, Graham NM, McArthur JH, Selnes OA, Jacobson LP et al (1993) Dementia in AIDS patients: incidence and risk factors. Multicenter AIDS Cohort Study. Neurology 43:2245–2252PubMedCrossRefGoogle Scholar
  29. McArthur JC, Haughey N, Gartner S, Conant K, Pardo C, Nath A, Sacktor N (2003) Human immunodeficiency virus-associated dementia: an evolving disease. J Neurovirol 9:205–221PubMedGoogle Scholar
  30. McMurtray A, Clark DG, Christine D, Mendez MF (2006) Early-onset dementia: frequency and causes compared to late-onset dementia. Dement Geriatr Cogn Disord 21:59–64PubMedCrossRefGoogle Scholar
  31. Morgan EE, Woods SP, Delano-Wood L, Bondi MW, Grant I (2011) Intraindividual variability in HIV infection: evidence for greater neurocognitive dispersion in older HIV seropositive adults. Neuropsychology 25:645–654PubMedCrossRefGoogle Scholar
  32. Mugavero MJ, Castellano C, Edelman D, Hicks C (2007) Late diagnosis of HIV infection: the role of age and sex. Am J Med 120:370–373PubMedCrossRefGoogle Scholar
  33. Nogueras M, Navarro G, Anton E, Sala M, Cervantes M, Amengual M, Segura F (2006) Epidemiological and clinical features, response to HAART, and survival in HIV-infected patients diagnosed at the age of 50 or more. BMC Infect Dis 6:159PubMedCrossRefGoogle Scholar
  34. Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD (1998) Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 338:853–860PubMedCrossRefGoogle Scholar
  35. Sacktor N, Lyles RH, Skolasky R, Kleeberger C, Selnes OA, Miller EN, Becker JT, Cohen B, McArthur JC (2001) HIV-associated neurologic disease incidence changes: Multicenter AIDS Cohort Study, 1990–1998. Neurology 56:257–260PubMedCrossRefGoogle Scholar
  36. Sacktor N, Skolasky R, Selnes OA, Watters M, Poff P, Shiramizu B, Shikuma C, Valcour V (2007) Neuropsychological test profile differences between young and old human immunodeficiency virus-positive individuals. J Neurovirol 13:203–209PubMedCrossRefGoogle Scholar
  37. Sacktor N, Skolasky RL, Cox C, Selnes O, Becker JT, Cohen B, Martin E, Miller EN (2010) Longitudinal psychomotor speed performance in human immunodeficiency virus-seropositive individuals: impact of age and serostatus. J Neurovirol 16:335–341PubMedCrossRefGoogle Scholar
  38. Scott J, Woods S, Carey C, Weber E, Bondi M, Grant I; The HIV Neurobehavioral Research Center (HNRC) Group (2011) Neurocognitive Consequences of HIV Infection in Older Adults: An Evaluation of the “Cortical” Hypothesis. AIDS Behavior 15(6):1187–1196Google Scholar
  39. Schweinsburg BC, Taylor MJ, Alhassoon OM, Gonzalez R, Brown GG, Ellis RJ, Letendre S, Videen JS, McCutchan JA, Patterson TL, Grant I (2005) Brain mitochondrial injury in human immunodeficiency virus-seropositive (HIV+) individuals taking nucleoside reverse transcriptase inhibitors. J Neurovirol 11:356–364PubMedCrossRefGoogle Scholar
  40. Smola S, Justice AC, Wagner J, Rabeneck L, Weissman S, Rodriguez-Barradas M (2001) Veterans aging cohort three-site study (VACS 3): overview and description. J Clin Epidemiol 54(Suppl 1):S61–S76PubMedCrossRefGoogle Scholar
  41. Stoff DM, Khalsa JH, Monjan A, Portegies P (2004) Introduction: HIV/AIDS and aging. AIDS 18(Suppl 1):S1–S2PubMedGoogle Scholar
  42. Thames AD, Kim MS, Becker BW, Foley JM, Hines LJ, Singer EJ, Heaton RK, Castellon SA, Hinkin CH (2011) Medication and finance management among HIV-infected adults: the impact of age and cognition. J Clin Exp Neuropsychol 33:200–209PubMedCrossRefGoogle Scholar
  43. The Antiretroviral Therapy Cohort Collaboration (2008) Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies. Lancet 372:293–299CrossRefGoogle Scholar
  44. Valcour V, Shikuma C, Shiramizu B, Watters M, Poff P, Selnes O, Holck P, Grove J, Sacktor N (2004a) Higher frequency of dementia in older HIV-1 individuals: the Hawaii Aging with HIV-1 Cohort. Neurology 63:822–827PubMedCrossRefGoogle Scholar
  45. Valcour V, Shikuma C, Shiramizu B, Watters M, Poff P, Selnes OA, Grove J, Liu Y, Abdul-Majid KB, Gartner S, Sacktor N (2004b) Age, apolipoprotein E4, and the risk of HIV dementia: the Hawaii Aging with HIV Cohort. J Neuroimmunol 157:197–202PubMedCrossRefGoogle Scholar
  46. Valcour V, Shikuma C, Watters M, Sacktor N (2004c) Cognitive impairment in older HIV-1-seropositive individuals: prevalence and potential mechanisms. AIDS 18(Suppl 1):S79–S86PubMedGoogle Scholar
  47. Valcour V, Shikuma CM, Shiramizu BT, Williams AE, Watters MR, Poff PW, Grove JS, Selnes OA, Sacktor NC (2005) Diabetes, insulin resistance, and dementia among HIV-1-infected patients. J Acquir Immune Defic Syndr 38:31–36PubMedCrossRefGoogle Scholar
  48. Valcour V, Watters MR, Williams AE, Sacktor N, McMurtray A, Shikuma C (2008) Aging exacerbates extrapyramidal motor signs in the era of highly active antiretroviral therapy. J Neurovirol 14:362–367PubMedCrossRefGoogle Scholar
  49. Valcour V, Paul R, Neuhaus J, Shikuma C (2011) The effects of age and HIV on neuropsychological performance. J Int Neuropsychol Soc 17:190–195PubMedCrossRefGoogle Scholar
  50. Valcour V, Chiao S, Rosen HJ, Nicolas K, Wendelken LA, Alcantar O, Rankin KP, Nir TM, Thompson PM, Miller B (2012) Functional deficits identified in patients with asymptomatic neurocognitive impairment (ANI) track to changes in brain integrity and size. Presented at the 19th Conference on Retroviruses and Opportunistic Infections (CROI), Seattle, 5–8 March 2012Google Scholar
  51. van Gorp WG, Satz P, Hinkin C, Selnes O, Miller EN, McArthur J, Cohen B, Paz D (1991) Metacognition in HIV-1 seropositive asymptomatic individuals: self-ratings versus objective neuropsychological performance. Multicenter AIDS Cohort Study (MACS). J Clin Exp Neuropsychol 13:812–819PubMedCrossRefGoogle Scholar
  52. van Gorp WG, Miller EN, Marcotte TD, Dixon W, Paz D, Selnes O, Wesch J, Becker JT, Hinkin CH, Mitrushina M et al (1994) The relationship between age and cognitive impairment in HIV-1 infection: findings from the Multicenter AIDS Cohort Study and a clinical cohort. Neurology 44:929–935PubMedCrossRefGoogle Scholar
  53. Vance DE, Childs G, Moneyham L, McKie-Bell P (2009) Successful aging with HIV: a brief overview for nursing. J Gerontol Nurs 35:19–25, quiz 26–7PubMedCrossRefGoogle Scholar
  54. Wilkie FL, Goodkin K, Khamis I, van Zuilen MH, Lee D, Lecusay R, Concha M, Symes S, Suarez P, Eisdorfer C (2003) Cognitive functioning in younger and older HIV-1-infected adults. J Acquir Immune Defic Syndr 33(Suppl 2):S93–S105PubMedGoogle Scholar
  55. Wilkins JW, Robertson KR, Snyder CR, Robertson WK, van der Horst C, Hall CD (1991) Implications of self-reported cognitive and motor dysfunction in HIV-positive patients. Am J Psychiatry 148:641–643PubMedGoogle Scholar
  56. Woods SP, Moore DJ, Weber E, Grant I (2009) Cognitive neuropsychology of HIV-associated neurocognitive disorders. Neuropsychol Rev 19:152–168PubMedCrossRefGoogle Scholar
  57. Zablotsky D, Kennedy M (2003) Risk factors and HIV transmission to midlife and older women: knowledge, options, and the initiation of safer sexual practices. J Acquir Immune Defic Syndr 33(Suppl 2):S122–S130PubMedGoogle Scholar

Copyright information

© Journal of NeuroVirology, Inc. 2012

Authors and Affiliations

  1. 1.Memory and Aging Center, Department of NeurologyUCSFSan FranciscoUSA
  2. 2.Division of Geriatric Medicine, Department of MedicineUCSFSan FranciscoUSA

Personalised recommendations