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Mechanisms of Cognitive Aging in the HIV-Positive Adult

  • Geropsychiatry & Cognitive Disorders of Late Life (P Newhouse, Section Editor)
  • Published:
Current Behavioral Neuroscience Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

As of the year 2016, an estimated 50% of the US HIV-positive population is aged 50 years or older. Due to a combination of increased rates of infection in older adults, and successful anti-retroviral (ART) regimens allowing HIV-positive adults to survive for decades with the disease, we are now faced with a steadily graying HIV-positive population, with only limited knowledge of how the cognitive and physiological effects of aging intersect with those of chronic HIV infection.

Recent Findings

Age-related changes to mood, cognition, and neurological health may be experienced differently in those living with HIV, and research concerning quality of life, mental health, and cognitive aging needs to account for and explore these factors more carefully in the coming years.

Summary

This review will explore the topic of cognitive aging with HIV: (1) central nervous system (CNS) infection of HIV and how the virus affects brain integrity and function; (2) cognitive and behavioral symptoms of HIV-associated neurocognitive disorders (HAND); (3) neurobiological theories of cognitive aging and how these processes may be exacerbated by HIV infection; and (4) clinical implications and complications of aging with HIV and factors that may result in poorer cognitive outcomes.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Torian L, Chen M, Hall IH. HIV surveillance—United States, 1981–2008. Centers for DIsease Control and Prevention: Morbidity and Mortality Weekly Report. 2011;60(21):689–93.

    Google Scholar 

  2. Vance DE, McGuinness T, Musgrove K, Orel NA, Fazeli PL. Successful aging and the epidemiology of HIV. Clin Interv Aging. 2011;6:181–92.

    Article  PubMed  PubMed Central  Google Scholar 

  3. • Chan P, Brew BJ. HIV associated neurocognitive disorders in the modern antiviral treatment era: prevalence, characteristics, biomarkers, and effects of treatment. Current HIV/AIDS reports. 2014;11(3):317–24. Comprehensive review addressing the milder persistent cognitive impairments associated with HIV, despite effective anti-retroviral therapy.

    Article  PubMed  Google Scholar 

  4. Gonzalez-Scarano F, Martin-Garcia J. The neuropathogenesis of AIDS. Nat Rev Immunol. 2005;5(1):69–81.

    Article  CAS  PubMed  Google Scholar 

  5. Anthony IC, Ramage SN, Carnie FW, Simmonds P, Bell JE. Influence of HAART on HIV-related CNS disease and neuroinflammation. J Neuropathol Exp Neurol. 2005;64(6):529–36.

    Article  CAS  PubMed  Google Scholar 

  6. Crum-Cianflone NF, Moore DJ, Letendre S, Poehlman Roediger M, Eberly L, Weintrob A, et al. Low prevalence of neurocognitive impairment in early diagnosed and managed HIV-infected persons. Neurology. 2013;80(4):371–9.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Garden GA. Microglia in human immunodeficiency virus-associated neurodegeneration. Glia. 2002;40(2):240–51.

    Article  PubMed  Google Scholar 

  8. Kaul M, Lipton SA. Chemokines and activated macrophages in HIV gp120-induced neuronal apoptosis. Proc Natl Acad Sci U S A. 1999;96(14):8212–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Zauli G, Secchiero P, Rodella L, Gibellini D, Mirandola P, Mazzoni M, et al. HIV-1 Tat-mediated inhibition of the tyrosine hydroxylase gene expression in dopaminergic neuronal cells. J Biol Chem. 2000;275(6):4159–65.

    Article  CAS  PubMed  Google Scholar 

  10. Grant I. Neurocognitive disturbances in HIV. Int Rev Psychiatry. 2008;20(1):33–47.

    Article  PubMed  Google Scholar 

  11. Harezlak J, Buchthal S, Taylor M, Schifitto G, Zhong J, Daar E, et al. Persistence of HIV-associated cognitive impairment, inflammation, and neuronal injury in era of highly active antiretroviral treatment. AIDS. 2011;25(5):625–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. •• Pfefferbaum A, Rogosa DA, Rosenbloom MJ, Chu W, Sassoon SA, Kemper CA, et al. Accelerated aging of selective brain structures in human immunodeficiency virus infection: a controlled, longitudinal magnetic resonance imaging study. Neurobiol Aging. 2014;35(7):1755–68. Study examining the combined deleterious effects of HIV and aging on brain tissue volume, likely associated with more severe and premature cognitive impairments relative to HIV-negative older adults.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Melrose RJ, Tinaz S, Castelo JM, Courtney MG, Stern CE. Compromised fronto-striatal functioning in HIV: an fMRI investigation of semantic event sequencing. Behav Brain Res. 2008;188(2):337–47.

    Article  PubMed  Google Scholar 

  14. Ipser JC, Brown GG, Bischoff-Grethe A, Connolly CG, Ellis RJ, Heaton RK, et al. HIV infection is associated with attenuated frontostriatal intrinsic connectivity: a preliminary study. J Int Neuropsychol Soc. 2015;21(3):203–13.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Castelo JM, Sherman SJ, Courtney MG, Melrose RJ, Stern CE. Altered hippocampal-prefrontal activation in HIV patients during episodic memory encoding. Neurology. 2006;66(11):1688–95.

    Article  CAS  PubMed  Google Scholar 

  16. Sullivan EV, Rosenbloom MJ, Rohlfing T, Kemper CA, Deresinski S, Pfefferbaum A. Pontocerebellar contribution to postural instability and psychomotor slowing in HIV infection without dementia. Brain imaging and behavior. 2011;5(1):12–24.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Itoh K, Mehraein P, Weis S. Neuronal damage of the substantia nigra in HIV-1 infected brains. Acta Neuropathol. 2000;99(4):376–84.

    Article  CAS  PubMed  Google Scholar 

  18. Ernst T, Chang L, Jovicich J, Ames N, Arnold S. Abnormal brain activation on functional MRI in cognitively asymptomatic HIV patients. Neurology. 2002;59(9):1343–9.

    Article  CAS  PubMed  Google Scholar 

  19. Chang L, Wong V, Nakama H, Watters M, Ramones D, Miller EN, et al. Greater than age-related changes in brain diffusion of HIV patients after 1 year. J NeuroImmune Pharmacol. 2008;3(4):265–74.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Wang X, Foryt P, Ochs R, Chung JH, Wu Y, Parrish T, et al. Abnormalities in resting-state functional connectivity in early human immunodeficiency virus infection. Brain connectivity. 2011;1(3):207–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kallianpur KJ, Kirk GR, Sailasuta N, Valcour V, Shiramizu B, Nakamoto BK, et al. Regional cortical thinning associated with detectable levels of HIV DNA. Cereb Cortex. 2011;

  22. Thompson PM, Dutton RA, Hayashi KM, Toga AW, Lopez OL, Aizenstein HJ, et al. Thinning of the cerebral cortex visualized in HIV/AIDS reflects CD4+ T lymphocyte decline. Proc Natl Acad Sci U S A. 2005;102(43):15647–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. • Wendelken LA, Jahanshad N, Rosen HJ, Busovaca E, Allen I, Coppola G, et al. ApoE epsilon4 is associated with cognition, brain integrity, and atrophy in HIV over age 60. J Acquir Immune Defic Syndr. 2016;73(4):426–32. This study is one of the few associating the Alzheimer’s disease risk gene with higher incidence of cognitive deficits and increased white matter atrophy in the brains of HIV-positive older adults.

    Article  CAS  PubMed  Google Scholar 

  24. Valcour V, Shikuma C, Shiramizu B, Watters M, Poff P, Selnes OA, et al. Age, apolipoprotein E4, and the risk of HIV dementia: the Hawaii aging with HIV cohort. J Neuroimmunol. 2004;157(1–2):197–202.

    Article  CAS  PubMed  Google Scholar 

  25. Green DA, Masliah E, Vinters HV, Beizai P, Moore DJ, Achim CL. Brain deposition of beta-amyloid is a common pathologic feature in HIV positive patients. AIDS. 2005;19(4):407–11.

    Article  CAS  PubMed  Google Scholar 

  26. Ellis RJ, Badiee J, Vaida F, Letendre S, Heaton RK, Clifford D, et al. CD4 nadir is a predictor of HIV neurocognitive impairment in the era of combination antiretroviral therapy. AIDS. 2011;25(14):1747–51.

    Article  CAS  PubMed  Google Scholar 

  27. Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M, et al. Updated research nosology for HIV-associated neurocognitive disorders. Neurology. 2007;69(18):1789–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Baldewicz TT, Leserman J, Silva SG, Petitto JM, Golden RN, Perkins DO, et al. Changes in neuropsychological functioning with progression of HIV-1 infection: results of an 8-year longitudinal investigation. AIDS Behav. 2004;8(3):345–55.

    Article  PubMed  Google Scholar 

  29. Alexaki A, Liu Y, Wigdahl B. Cellular reservoirs of HIV-1 and their role in viral persistence. Curr HIV Res. 2008;6(5):388–400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Le Saux S, Weyand CM, Goronzy JJ. Mechanisms of immunosenescence: lessons from models of accelerated immune aging. Ann N Y Acad Sci. 2012;1247:69–82.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Woods SP, Moore DJ, Weber E, Grant I. Cognitive neuropsychology of HIV-associated neurocognitive disorders. Neuropsychol Rev. 2009;19(2):152–68.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Maruff P, Malone V, McArthur-Jackson C, Mulhall B, Benson E, Currie J. Abnormalities of visual spatial attention in HIV infection and the HIV-associated dementia complex. J Neuropsychiatry Clin Neurosci. 1995;7(3):325–33.

    Article  CAS  PubMed  Google Scholar 

  33. York MK, Franks JJ, Henry RR, Hamilton WJ. Verbal working memory storage and processing deficits in HIV-1 asymptomatic and symptomatic individuals. Psychol Med. 2001;31(7):1279–91.

    Article  CAS  PubMed  Google Scholar 

  34. Schiller A, Foley J, Burns W, Sellers AL, Golden C. Subcortical profile of memory compromise among HIV-1-infected individuals. The International journal of neuroscience. 2009;119(10):1779–803.

    Article  PubMed  Google Scholar 

  35. Towgood KJ, Pitkanen M, Kulasegaram R, Fradera A, Kumar A, Soni S, et al. Mapping the brain in younger and older asymptomatic HIV-1 men: frontal volume changes in the absence of other cortical or diffusion tensor abnormalities. Cortex. 2012;48(2):230–41.

    Article  PubMed  Google Scholar 

  36. Chang L, Holt JL, Yakupov R, Jiang CS, Ernst T. Lower cognitive reserve in the aging human immunodeficiency virus-infected brain. Neurobiol Aging. 2013;34(4):1240–53.

    Article  PubMed  Google Scholar 

  37. Becker JT, Lopez OL, Dew MA, Aizenstein HJ. Prevalence of cognitive disorders differs as a function of age in HIV virus infection. AIDS. 2004;18(Suppl 1):S11–8.

    Article  PubMed  Google Scholar 

  38. Iudicello JE, Woods SP, Deutsch R, Grant I, Group H. Combined effects of aging and HIV infection on semantic verbal fluency: a view of the cortical hypothesis through the lens of clustering and switching. J Clin Exp Neuropsychol. 2012;34(5):476–88.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Valcour V, Paul R, Neuhaus J, Shikuma C. The effects of age and HIV on neuropsychological performance. J Int Neuropsychol Soc. 2011;17(1):190–5.

    Article  PubMed  Google Scholar 

  40. Cysique LA, Maruff P, Bain MP, Wright E, Brew BJ. HIV and age do not substantially interact in HIV-associated neurocognitive impairment. J Neuropsychiatry Clin Neurosci. 2011;23(1):83–9.

    Article  PubMed  Google Scholar 

  41. Ances BM, Ellis RJ. Dementia and neurocognitive disorders due to HIV-1 infection. Semin Neurol. 2007;27(1):86–92.

    Article  PubMed  Google Scholar 

  42. Vidal-Pineiro D, Valls-Pedret C, Fernandez-Cabello S, Arenaza-Urquijo EM, Sala-Llonch R, Solana E, et al. Decreased default mode network connectivity correlates with age-associated structural and cognitive changes. Front Aging Neurosci. 2014;6:256.

    PubMed  PubMed Central  Google Scholar 

  43. Grady C. The cognitive neuroscience of ageing. Nat Rev Neurosci. 2012;13(7):491–505.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Young-Bernier M, Kamil Y, Tremblay F, Davidson PS. Associations between a neurophysiological marker of central cholinergic activity and cognitive functions in young and older adults. Behavioral and brain functions : BBF. 2012;8:17.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Betzel RF, Byrge L, He Y, Goni J, Zuo XN, Sporns O. Changes in structural and functional connectivity among resting-state networks across the human lifespan. NeuroImage. 2014;102(Pt 2):345–57.

    Article  PubMed  Google Scholar 

  46. Davis SW, Dennis NA, Daselaar SM, Fleck MS, Cabeza R. Que PASA? The posterior-anterior shift in aging. Cereb Cortex. 2008;18(5):1201–9.

    Article  PubMed  Google Scholar 

  47. Goh JO. Functional dedifferentiation and altered connectivity in older adults: neural accounts of cognitive aging. Aging and disease. 2011;2(1):30–48.

    PubMed  PubMed Central  Google Scholar 

  48. Freeman GB, Gibson GE. Dopamine, acetylcholine, and glutamate interactions in aging behavioral and neurochemical correlates. Ann N Y Acad Sci. 1988;515:191–202.

    Article  CAS  PubMed  Google Scholar 

  49. Warburton DM, Rusted JM. Cholinergic control of cognitive resources. Neuropsychobiology. 1993;28(1–2):43–6.

    CAS  PubMed  Google Scholar 

  50. Bartus RT, Dean RL 3rd, Beer B, Lippa AS. The cholinergic hypothesis of geriatric memory dysfunction. Science. 1982;217(4558):408–14.

    Article  CAS  PubMed  Google Scholar 

  51. Ellis JR, Ellis KA, Bartholomeusz CF, Harrison BJ, Wesnes KA, Erskine FF, et al. Muscarinic and nicotinic receptors synergistically modulate working memory and attention in humans. Int J Neuropsychopharmacol. 2006:175–89.

  52. Chau DT, Roth RM, Green AI. The neural circuitry of reward and its relevance to psychiatric disorders. Curr Psychiatry Rep. 2004;6(5):391–9.

    Article  PubMed  Google Scholar 

  53. Hollerman JR, Tremblay L, Schultz W. Involvement of basal ganglia and orbitofrontal cortex in goal-directed behavior. Prog Brain Res. 2000;126:193–215.

    Article  CAS  PubMed  Google Scholar 

  54. Owen AM, Iddon JL, Hodges JR, Summers BA, Robbins TW. Spatial and non-spatial working memory at different stages of Parkinson’s disease. Neuropsychologia. 1997;35(4):519–32.

    Article  CAS  PubMed  Google Scholar 

  55. Muller U, von Cramon DY, Pollmann S. D1- versus D2-receptor modulation of visuospatial working memory in humans. J Neurosci. 1998;18(7):2720–8.

    CAS  PubMed  Google Scholar 

  56. Marie RM, Barre L, Dupuy B, Viader F, Defer G, Baron JC. Relationships between striatal dopamine denervation and frontal executive tests in Parkinson’s disease. Neurosci Lett. 1999;260(2):77–80.

    Article  CAS  PubMed  Google Scholar 

  57. Volkow ND, Gur RC, Wang GJ, Fowler JS, Moberg PJ, Ding YS, et al. Association between decline in brain dopamine activity with age and cognitive and motor impairment in healthy individuals. Am J Psychiatry. 1998;155(3):344–9.

    CAS  PubMed  Google Scholar 

  58. Erixon-Lindroth N, Farde L, Wahlin TB, Sovago J, Halldin C, Backman L. The role of the striatal dopamine transporter in cognitive aging. Psychiatry Res. 2005;138(1):1–12.

    Article  CAS  PubMed  Google Scholar 

  59. Levin ED, Rose JE. Acute and chronic nicotinic interactions with dopamine systems and working memory performance. Ann N Y Acad Sci. 1995;757:245–52.

    Article  CAS  PubMed  Google Scholar 

  60. Dumas JA, Newhouse PA. The cholinergic hypothesis of cognitive aging revisited again: cholinergic functional compensation. Pharmacol Biochem Behav. 2011;99(2):254–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Anglade P, Vyas S, Hirsch EC, Agid Y. Apoptosis in dopaminergic neurons of the human substantia nigra during normal aging. Histol Histopathol. 1997;12(3):603–10.

    CAS  PubMed  Google Scholar 

  62. Newhouse PA, Potter A, Corwin J, Lenox R. Age-related effects of the nicotinic antagonist mecamylamine on cognition and behavior. Neuropsychopharmacology. 1994;10(2):93–107.

    Article  CAS  PubMed  Google Scholar 

  63. Vitiello B, Martin A, Hill J, Mack C, Molchan S, Martinez R, et al. Cognitive and behavioral effects of cholinergic, dopaminergic, and serotonergic blockade in humans. Neuropsychopharmacology. 1997;16(1):15–24.

    Article  CAS  PubMed  Google Scholar 

  64. Drachman DA, Noffsinger D, Sahakian BJ, Kurdziel S, Fleming P. Aging, memory, and the cholinergic system: a study of dichotic listening. Neurobiol Aging. 1980;1(1):39–43.

    Article  CAS  PubMed  Google Scholar 

  65. Schliebs R, Arendt T. The cholinergic system in aging and neuronal degeneration. Behav Brain Res. 2011;221(2):555–63.

    Article  CAS  PubMed  Google Scholar 

  66. Sunderland T, Tariot PN, Newhouse PA. Differential responsivity of mood, behavior, and cognition to cholinergic agents in elderly neuropsychiatric populations. Brain Res. 1988;472(4):371–89.

    Article  CAS  PubMed  Google Scholar 

  67. Mihailescu S, Drucker-Colin R. Nicotine, brain nicotinic receptors, and neuropsychiatric disorders. Arch Med Res. 2000;31(2):131–44.

    Article  CAS  PubMed  Google Scholar 

  68. Picciotto MR, Zoli M. Nicotinic receptors in aging and dementia. J Neurobiol. 2002;53(4):641–55.

    Article  CAS  PubMed  Google Scholar 

  69. Nieoullon A. Dopamine and the regulation of cognition and attention. Prog Neurobiol. 2002;67(1):53–83.

    Article  CAS  PubMed  Google Scholar 

  70. Vink M, Kleerekooper I, van den Wildenberg WP, Kahn RS. Impact of aging on frontostriatal reward processing. Hum Brain Mapp. 2015;36(6):2305–17.

    Article  PubMed  Google Scholar 

  71. Tsang J, Fullard JF, Giakoumaki SG, Katsel P, Katsel P, Karagiorga VE, et al. The relationship between dopamine receptor D1 and cognitive performance. NPJ schizophrenia. 2015;1:14002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Stelzel C, Fiebach CJ, Cools R, Tafazoli S, D’Esposito M. Dissociable fronto-striatal effects of dopamine D2 receptor stimulation on cognitive versus motor flexibility. Cortex. 2013;49(10):2799–811.

    Article  PubMed  Google Scholar 

  73. Bolton JL, Marioni RE, Deary IJ, Harris SE, Stewart MC, Murray GD, et al. Association between polymorphisms of the dopamine receptor D2 and catechol-o-methyl transferase genes and cognitive function. Behav Genet. 2010;40(5):630–8.

    Article  PubMed  Google Scholar 

  74. Nyberg L, Karalija N, Salami A, Andersson M, Wåhlin A, Kaboovand N, et al. Dopamine D2 receptor availability is linked to hippocampal–caudate functional connectivity and episodic memory. Proc Natl Acad Sci. 2016;113(28):7918–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Abdulrahman H, Fletcher PC, Bullmore E, Morcom AM. Dopamine and memory dedifferentiation in aging. Neuroimage. 2015;

  76. Guitart-Masip M, Salami A, Garrett D, Rieckmann A, Lindenberger U, Backman L. BOLD variability is related to dopaminergic neurotransmission and cognitive aging. Cereb Cortex. 2016;26(5):2074–83.

    Article  PubMed  Google Scholar 

  77. Zhang S, Hu S, Chao HH, Li CS. Resting-state functional connectivity of the locus coeruleus in humans: in comparison with the ventral tegmental area/substantia nigra pars compacta and the effects of age. Cereb Cortex. 2016;26(8):3413–27.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Papenberg G, Backman L, Nagel IE, Nietfeld W, Schroder J, Bertram L, et al. COMT polymorphism and memory dedifferentiation in old age. Psychol Aging. 2014;29(2):374–83.

    Article  PubMed  Google Scholar 

  79. Anderson BA, Kronemer SI, Rilee JJ, Sacktor N, Marvel CL. Reward, attention, and HIV-related risk in HIV+ individuals. Neurobiol Dis. 2016;92(Pt B):157–65.

    Article  PubMed  Google Scholar 

  80. Bracci L, Lozzi L, Rustici M, Neri P. Binding of HIV-1 gp120 to the nicotinic receptor. FEBS Lett. 1992;311(2):115–8.

    Article  CAS  PubMed  Google Scholar 

  81. Ballester LY, Capo-Velez CM, Garcia-Beltran WF, Ramos FM, Vazquez-Rosa E, Rios R, et al. Up-regulation of the neuronal nicotinic receptor alpha7 by HIV glycoprotein 120: potential implications for HIV-associated neurocognitive disorder. J Biol Chem. 2012;287(5):3079–86.

    Article  CAS  PubMed  Google Scholar 

  82. Agrawal L, Louboutin JP, Marusich E, Reyes BA, Van Bockstaele EJ, Strayer DS. Dopaminergic neurotoxicity of HIV-1 gp120: reactive oxygen species as signaling intermediates. Brain Res. 2010;1306:116–30.

    Article  CAS  PubMed  Google Scholar 

  83. Banks WA, Robinson SM, Nath A. Permeability of the blood-brain barrier to HIV-1 Tat. Exp Neurol. 2005;193(1):218–27.

    Article  CAS  PubMed  Google Scholar 

  84. Aylward EH, Henderer JD, McArthur JC, Brettschneider PD, Harris GJ, Barta PE, et al. Reduced basal ganglia volume in HIV-1-associated dementia: results from quantitative neuroimaging. Neurology. 1993;43(10):2099–104.

    Article  CAS  PubMed  Google Scholar 

  85. Kumar AM, Fernandez JB, Singer EJ, Commins D, Waldrop-Valverde D, Ownby RL, et al. Human immunodeficiency virus type 1 in the central nervous system leads to decreased dopamine in different regions of postmortem human brains. J Neuro-Oncol. 2009;15(3):257–74.

    CAS  Google Scholar 

  86. Ances BM, Ortega M, Vaida F, Heaps J, Paul R. Independent effects of HIV, aging, and HAART on brain volumetric measures. J Acquir Immune Defic Syndr. 2012;59(5):469–77.

    Article  PubMed  PubMed Central  Google Scholar 

  87. DeVaughn S, Muller-Oehring EM, Markey B, Bronte-Stewart HM, Schulte T. Aging with HIV-1 infection: motor functions, cognition, and attention—a comparison with Parkinson’s disease. Neuropsychol Rev. 2015;25(4):424–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Alisky JM. The coming problem of HIV-associated Alzheimer’s disease. Med Hypotheses. 2007;69(5):1140–3.

    Article  CAS  PubMed  Google Scholar 

  89. Moulignier A, Gueguen A, Lescure FX, Ziegler M, Girard PM, Cardon B, et al. Does HIV infection alter Parkinson disease? J Acquir Immune Defic Syndr. 2015;70(2):129–36.

    Article  CAS  PubMed  Google Scholar 

  90. Ciccarelli N, Limiti S, Fabbiani M, Baldonero E, Milanini B, Lamonica S, et al. Verbal list learning and memory profiles in HIV-infected adults, Alzheimer’s disease, and Parkinson's disease: an evaluation of the “cortical hypothesis” of NeuroAIDS. Applied neuropsychology Adult. 2016:1–10.

  91. Crane MK, Bogner HR, Brown GK, Gallo JJ. The link between depressive symptoms, negative cognitive bias and memory complaints in older adults. Aging Ment Health. 2007;11(6):708–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Alexopoulos GS. Depression in the elderly. Lancet. 2005;365(9475):1961–70.

    Article  Google Scholar 

  93. Sexton CE, McDermott L, Kalu UG, Herrmann LL, Bradley KM, Allan CL, et al. Exploring the pattern and neural correlates of neuropsychological impairment in late-life depression. Psychol Med. 2012;42(6):1195–202.

    Article  CAS  PubMed  Google Scholar 

  94. • Moore RC, Fazeli PL, Jeste DV, Moore DJ, Grant I, Woods SP, et al. Successful cognitive aging and health-related quality of life in younger and older adults infected with HIV. AIDS Behav. 2014;18(6):1186–97. This study addresses how HIV status and related cognitive deficits affect neuropsychological, psychiatric, and behavioral markers of quality of life differently in younger versus older HIV-positive patients.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Milanini B, Catella S, Perkovich B, Esmaeili-Firidouni P, Wendelken L, Paul R et al. Psychiatric symptom burden in older people living with HIV with and without cognitive impairment: the UCSF HIV over 60 cohort study. AIDS Care. 2017:1–8.

  96. Justice AC, McGinnis KA, Atkinson JH, Heaton RK, Young C, Sadek J, et al. Psychiatric and neurocognitive disorders among HIV-positive and negative veterans in care: veterans aging cohort five-site study. AIDS. 2004;18(Suppl 1):S49–59.

    Article  PubMed  Google Scholar 

  97. Majeed Z, van Wijngaarden E, Dolan JG, Shah KN. Depression partially mediated the relationship between basic psychological needs and quality of life among people living with HIV. AIDS Care. 2017:1–5.

  98. Fumaz CR, Munoz-Moreno JA, Ferrer MJ, Gonzalez-Garcia M, Negredo E, Perez-Alvarez N, et al. Emotional impact of premature aging symptoms in long-term treated HIV-infected subjects. J Acquir Immune Defic Syndr. 2012;59(1):e5–8.

    Article  PubMed  Google Scholar 

  99. Salem LC, Vogel A, Ebstrup J, Linneberg A, Waldemar G. Subjective cognitive complaints included in diagnostic evaluation of dementia helps accurate diagnosis in a mixed memory clinic cohort. Int J Geriatr Psychiatry. 2015;30(12):1177–85.

    Article  CAS  PubMed  Google Scholar 

  100. Thompson CL, Henry JD, Rendell PG, Withall A, Brodaty H. How valid are subjective ratings of prospective memory in mild cognitive impairment and early dementia? Gerontology. 2015;61(3):251–7.

    Article  PubMed  Google Scholar 

  101. Yates JA, Clare L, Woods RT, Matthews FE. Subjective memory complaints are involved in the relationship between mood and mild cognitive impairment. J Alzheimers Dis. 2015;48(Suppl 1):S115–23.

    Article  PubMed  Google Scholar 

  102. Chartier M, Crouch PC, Tullis V, Catella S, Frawley E, Filanosky C, et al. The Montreal Cognitive Assessment: a pilot study of a brief screening tool for mild and moderate cognitive impairment in HIV-positive veterans. Journal of the International Association of Providers of AIDS Care. 2015;14(3):197–201.

    Article  PubMed  Google Scholar 

  103. •• Kamkwalala A, Hulgan T, Newhouse P. Subjective memory complaints are associated with poorer cognitive performance in adults with HIV. AIDS Care. 2017;29(5):654–9. This study shows differences in the association between subjective memory complaints and objective cognitive performance in HIV-positive adults versus HIV-negative adults.

    Article  PubMed  Google Scholar 

  104. Chang L, Jiang C, Cunningham E, Buchthal S, Douet V, Andres M, et al. Effects of APOE epsilon4, age, and HIV on glial metabolites and cognitive deficits. Neurology. 2014;82(24):2213–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Alisky JM. Could cholinesterase inhibitors and memantine alleviate HIV dementia? J Acquir Immune Defic Syndr. 2005;38(1):113–4.

    Article  PubMed  Google Scholar 

  106. Giunta B, Ehrhart J, Townsend K, Sun N, Vendrame M, Shytle D, et al. Galantamine and nicotine have a synergistic effect on inhibition of microglial activation induced by HIV-1 gp120. Brain Res Bull. 2004;64(2):165–70.

    Article  CAS  PubMed  Google Scholar 

  107. Simioni S, Cavassini M, Annoni JM, Metral M, Iglesias K, Rimbault Abraham A, et al. Rivastigmine for HIV-associated neurocognitive disorders: a randomized crossover pilot study. Neurology. 2013;80(6):553–60.

    Article  CAS  PubMed  Google Scholar 

  108. Valdes-Ferrer SI, Crispin JC, Belaunzaran PF, Cantu-Brito CG, Sierra-Madero J, Alcocer-Varela J. Acetylcholine-esterase inhibitor pyridostigmine decreases T cell overactivation in patients infected by HIV. AIDS Res Hum Retrovir. 2009;25(8):749–55.

    Article  CAS  PubMed  Google Scholar 

  109. Gotti C, Fornasari D, Clementi F. Human neuronal nicotinic receptors. Prog Neurobiol. 1997;53(2):199–237.

    Article  CAS  PubMed  Google Scholar 

  110. Wonnacott S, Soliakov L, Wilkie G, Redfern P, Marshall D. Presynaptic nicotinic acetylcholine receptors in the brain. Drug Develop Res. 1996;38(3–4):149–59.

    Article  CAS  Google Scholar 

  111. Marci M, Grilli M. Presynaptic nicotinic receptors modulating neurotransmitter release in the central nervous system: functional interactions with other coexisting receptors. Progress in Neurobiology. 2010:105–11.

  112. Wojna V, Robles L, Skolasky RL, Mayo R, Selnes O, de la Torre T, et al. Associations of cigarette smoking with viral immune and cognitive function in human immunodeficiency virus-seropositive women. J Neuro-Oncol. 2007;13(6):561–8.

    CAS  Google Scholar 

  113. Nesil T, Cao J, Yang Z, Chang SL, Li MD. Nicotine attenuates the effect of HIV-1 proteins on the neural circuits of working and contextual memories. Molecular brain. 2015;8:43.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  114. Kamkwalala A, Newhouse PA. Beyond acetylcholinesterase inhibitors: novel cholinergic treatments for Alzheimer’s disease. Curr Alzheimer Res. 2017;14(4):377–92.

    CAS  PubMed  Google Scholar 

  115. Hinkin CH, Castellon SA, Hardy DJ, Farinpour R, Newton T, Singer E. Methylphenidate improves HIV-1-associated cognitive slowing. J Neuropsychiatry Clin Neurosci. 2001;13(2):248–54.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the following funding sources: Vanderbilt CTSA NCATS UL1TR000445, Vanderbilt Center for AIDS Research Developmental Core Pilot Grant.

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Authors and Affiliations

  1. Vanderbilt University Center for Cognitive Medicine, Nashville, TN, USA

    Asante Kamkwalala & Paul Newhouse

  2. Veterans Affairs Tennessee Valley Healthcare System Geriatric Research, Education, and Clinical Center (VA TVHS GRECC), Nashville, TN, USA

    Paul Newhouse

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  1. Asante Kamkwalala
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  2. Paul Newhouse
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Correspondence to Paul Newhouse.

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Asante Kamkwalala and Dr. Paul Newhouse declare that they have no conflicts of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Geropsychiatry & Cognitive Disorders of Late Life

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Kamkwalala, A., Newhouse, P. Mechanisms of Cognitive Aging in the HIV-Positive Adult. Curr Behav Neurosci Rep 4, 188–197 (2017). https://doi.org/10.1007/s40473-017-0122-9

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