Top

Published in:

Open Access 01-12-2015 | Review

HIV effects on age-associated neurocognitive dysfunction: premature cognitive aging or neurodegenerative disease?

Authors: Ronald A Cohen, Talia R Seider, Bradford Navia

Published in: Alzheimer's Research & Therapy | Issue 1/2015

Abstract

Marked improvements in survival and health outcome for people infected with HIV have occurred since the advent of combination antiretroviral therapy over a decade ago. Yet HIV-associated neurocognitive disorders continue to occur with an alarming prevalence. This may reflect the fact that infected people are now living longer with chronic infection. There is mounting evidence that HIV exacerbates age-associated cognitive decline. Many middle-aged HIV-infected people are experiencing cognitive decline similar that to that found among much older adults. An increased prevalence of vascular and metabolic comorbidities has also been observed and is greatest among older adults with HIV. Premature age-associated neurocognitive decline appears to be related to structural and functional brain changes on neuroimaging, and of particular concern is the fact that pathology indicative of neurodegenerative disease has been shown to occur in the brains of HIV-infected people. Yet notable differences also exist between the clinical presentation and brain disturbances occurring with HIV and those occurring in neurodegenerative conditions such as Alzheimer’s disease. HIV interacts with the aging brain to affect neurological structure and function. However, whether this interaction directly affects neurodegenerative processes, accelerates normal cognitive aging, or contributes to a worsening of other comorbidities that affect the brain in older adults remains an open question. Evidence for and against each of these possibilities is reviewed.

Centers for Disease Control and Prevention. HIV surveillance report, 2011. Vol. 23. 2013:1–11. http://www.cdc.gov/hiv/topics/surveillance/resources/reports/. Accessed 14 May 2014.

Holland JC, Tross S. The psychosocial and neuropsychiatric sequelae of the acquired immunodeficiency syndrome and related disorders. Ann Intern Med. 1985;103:760–4.PubMed

Navia BA, Jordan BD, Price RW. The AIDS dementia complex: I. Clinical features. Ann Neurol. 1986;19:517–24.PubMed

Dorrell L, Snow MH, Ong EL. Mortality and survival trends in patients with AIDS in north east England from 1984–1992. J Infect. 1995;30:23–7.PubMed

Antiretroviral Therapy Cohort Collaboration. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies. Lancet. 2008;372:293–9.

Hall HI, Song R, Rhodes P, Prejean J, An Q, Lee LM, et al. Estimation of HIV incidence in the United States. JAMA. 2008;300:520–9.PubMedCentralPubMed

Bhaskaran K, Mussini C, Antinori A, Walker AS, Dorrucci M, Sabin C, et al. Changes in the incidence and predictors of human immunodeficiency virus-associated dementia in the era of highly active antiretroviral therapy. Ann Neurol. 2008;63:213–21.PubMed

Heaton RK, Grant I, Butters N, White DA, Kirson D, Atkinson JH, et al. The HNRC 500–neuropsychology of HIV infection at different disease stages. HIV Neurobehavioral Research Center. J Int Neuropsychol Soc. 1995;1:231–51.PubMed

Sacktor N, Bacellar H, Hoover D, Nance-Sproson T, Selness O, Miller E, et al. Psychomotor slowing in HIV infection: a predictor of dementia, AIDS & death. J Neurovirol. 1996;2:404–10.PubMed

10.

Neuenburg JK, Brodt HR, Herndier BG, Bickel M, Bacchetti P, Price RW, et al. HIV-related neuropathology, 1985 to 1999: rising prevalence of HIV encephalopathy in the era of highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2002;31:171–7.PubMed

11.

Brew BJ, Rosenblum M, Cronin K, Price RW. AIDS dementia complex and HIV-1 brain infection: clinical-virological correlations. Ann Neurol. 1995;38:563–70.PubMed

12.

Portegies P, de Gans J, Lange JM, Derix MM, Speelman H, Bakker M, et al. Declining incidence of AIDS dementia complex after introduction of zidovudine treatment. BMJ. 1989;299:819–21.PubMedCentralPubMed

13.

Cohen RA, Boland R, Paul R, Tashima KT, Schoenbaum EE, Celentano DD, et al. Neurocognitive performance enhanced by highly active antiretroviral therapy in HIV-infected women. AIDS. 2001;15:341–5.PubMed

14.

McArthur JC, McDermott MP, McClernon D, St Hillaire C, Conant K, Marder K, et al. Attenuated central nervous system infection in advanced HIV/AIDS with combination antiretroviral therapy. Arch Neurol. 2004;61:1687–96.PubMed

15.

Sacktor N, McDermott MP, Marder K, Schifitto G, Selnes OA, McArthur JC, et al. HIV-associated cognitive impairment before and after the advent of combination therapy. J Neurovirol. 2002;8:136–42.PubMed

16.

Heaton RK, Franklin DR, Ellis RJ, McCutchan JA, Letendre SL, Leblanc S, et al. HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirol. 2011;17:3–16.PubMedCentralPubMed

17.

Carey CL, Woods SP, Gonzalez R, Conover E, Marcotte TD, Grant I, et al. Predictive validity of global deficit scores in detecting neuropsychological impairment in HIV infection. J Clin Exp Neuropsychol. 2004;26:307–19.PubMed

18.

Osowiecki DM, Cohen RA, Morrow KM, Paul RH, Carpenter CC, Flanigan T, et al. Neurocognitive and psychological contributions to quality of life in HIV-1-infected women. AIDS. 2000;14:1327–32.PubMed

19.

Heaton RK, Marcotte TD, Mindt MR, Sadek J, Moore DJ, Bentley H, et al. The impact of HIV-associated neuropsychological impairment on everyday functioning. J Int Neuropsychol Soc. 2004;10:317–31.PubMed

20.

Lai DJ, Tarwater PM, Hardy RJ. Measuring the impact of HIV/AIDS, heart disease and malignant neoplasms on life expectancy in the USA from 1987 to 2000. Public Health. 2006;120:486–92.PubMed

21.

Wendelken LA, Valcour V. Impact of HIV and aging on neuropsychological function. J Neurovirol. 2012;18:256–63.PubMedCentralPubMed

22.

Valcour VG, Shikuma CM, Watters MR, Sacktor NC. Cognitive impairment in older HIV-1-seropositive individuals: prevalence and potential mechanisms. AIDS. 2004;18:S79–86.PubMedCentralPubMed

23.

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:S11–8.PubMed

24.

Wilkie FL, Goodkin K, Khamis I, van Zuilen MH, Lee D, Lecusay R, et al. Cognitive functioning in younger and older HIV-1-infected adults. J Acquir Immune Defic Syndr. 2003;33:S93–S105.PubMed

25.

Becker JT, Maruca V, Kingsley LA, Sanders JM, Alger JR, Barker PB, et al. Factors affecting brain structure in men with HIV disease in the post-HAART era. Neuroradiology. 2012;54:113–21.PubMedCentralPubMed

26.

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;59:469–77.PubMedCentralPubMed

27.

Seider TR, Luo X, Gongvatana A, Devlin KN, de la Monte SM, Chasman JD, et al. Verbal memory declines more rapidly with age in HIV infected versus uninfected adults. J Clin Exp Neuropsychol. 2014;36:356–67.PubMedCentralPubMed

28.

Morgan EE, Woods SP, Smith C, Weber E, Scott JC, Grant I. Lower cognitive reserve among individuals with syndromic HIV-associated neurocognitive disorders (HAND). AIDS Behav. 2012;16:2279–85.PubMedCentralPubMed

29.

Devlin KN, Gongvatana A, Clark US, Chasman JD, Westbrook ML, Tashima KT, et al. Neurocognitive effects of HIV, hepatitis C, and substance use history. J Int Neuropsychol Soc. 2012;18:68–78.PubMedCentralPubMed

30.

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;25:625–33.PubMedCentralPubMed

31.

Heaton RK, Clifford DB, Franklin Jr DR, Woods SP, Ake C, Vaida F, et al. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology. 2010;75:2087–96.PubMedCentralPubMed

32.

Cohen RA, Harezlak J, Gongvatana A, Buchthal S, Schifitto G, Clark U, et al. Cerebral metabolite abnormalities in human immunodeficiency virus are associated with cortical and subcortical volumes. J Neurovirol. 2010;16:435–44.PubMed

33.

Cohen RA, Harezlak J, Schifitto G, Hana G, Clark U, Gongvatana A, et al. Effects of nadir CD4 count and duration of human immunodeficiency virus infection on brain volumes in the highly active antiretroviral therapy era. J Neurovirol. 2010;16:25–32.PubMedCentralPubMed

34.

Hua X, Boyle CP, Harezlak J, Tate DF, Yiannoutsos CT, Cohen R, et al. Disrupted cerebral metabolite levels and lower nadir CD4 + counts are linked to brain volume deficits in 210 HIV-infected patients on stable treatment. Neuroimage Clin. 2013;3:132–42.PubMedCentralPubMed

35.

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;43:2099–104.PubMed

36.

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;102:15647–52.PubMedCentralPubMed

37.

Becker JT, Bajo R, Fabrizio M, Sudre G, Cuesta P, Aizenstein HJ, et al. Functional connectivity measured with magnetoencephalography identifies persons with HIV disease. Brain Imaging Behav. 2012;6:366–73.PubMedCentralPubMed

38.

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;48:230–41.PubMed

39.

Seider T, Cohen RA, Correia S, Gongvatana A, Cummings T, Tashima KT, et al. Synergistic effects of age and HIV on white matter hyperintensities [abstract]. Annual American Academy of Clinical Neuropsychology Conference. 25–28 June 2014; New York, NY.

40.

McMurtray A, Nakamoto B, Shikuma C, Valcour V. Cortical atrophy and white matter hyperintensities in HIV: the Hawaii Aging with HIV Cohort Study. J Stroke Cerebrovasc Dis. 2008;17:212–7.PubMedCentralPubMed

41.

Tate DF, Conley J, Paul RH, Coop K, Zhang S, Zhou W, et al. Quantitative diffusion tensor imaging tractography metrics are associated with cognitive performance among HIV-infected patients. Brain Imaging Behav. 2010;4:68–79.PubMedCentralPubMed

42.

Gongvatana A, Cohen RA, Correia S, Devlin KN, Miles J, Kang H, et al. Clinical contributors to cerebral white matter integrity in HIV-infected individuals. J Neurovirol. 2011;17:477–86.PubMedCentralPubMed

43.

Gongvatana A, Schweinsburg BC, Taylor MJ, Theilmann RJ, Letendre SL, Alhassoon OM, et al. White matter tract injury and cognitive impairment in human immunodeficiency virus-infected individuals. J Neurovirol. 2009;15:187–95.PubMedCentralPubMed

44.

Pomara N, Crandall DT, Choi SJ, Johnson G, Lim KO. White matter abnormalities in HIV-1 infection: a diffusion tensor imaging study. Psychiatry Res. 2001;106:15–24.PubMed

45.

Ragin AB, Wu Y, Storey P, Cohen BA, Edelman RR, Epstein LG. Diffusion tensor imaging of subcortical brain injury in patients infected with human immunodeficiency virus. J Neurovirol. 2005;11:292–8.PubMedCentralPubMed

46.

Harezlak J, Cohen R, Gongvatana A, Taylor M, Buchthal S, Schifitto G, et al. Predictors of CNS injury as measured by proton magnetic resonance spectroscopy in the setting of chronic HIV infection and CART. J Neurovirol. 2014;20:294–303.PubMed

47.

Paul RH, Ernst T, Brickman AM, Yiannoutsos CT, Tate DF, Cohen RA, et al. Relative sensitivity of magnetic resonance spectroscopy and quantitative magnetic resonance imaging to cognitive function among nondemented individuals infected with HIV. J Int Neuropsychol Soc. 2008;14:725–33.PubMed

48.

Cysique LA, Moffat K, Moore DM, Lane TA, Davies NW, Carr A, et al. HIV, vascular and aging injuries in the brain of clinically stable HIV-infected adults: a (1)H MRS study. PLoS One. 2013;8:e61738.PubMedCentralPubMed

49.

von Giesen HJ, Antke C, Hefter H, Wenserski F, Seitz RJ, Arendt G. Potential time course of human immunodeficiency virus type 1-associated minor motor deficits: electrophysiologic and positron emission tomography findings. Arch Neurol. 2000;57:1601–7.

50.

Palmer CS, Ostrowski M, Gouillou M, Tsai L, Yu D, Zhou J, et al. Increased glucose metabolic activity is associated with CD4+ T-cell activation and depletion during chronic HIV infection. AIDS. 2014;28:297–309.PubMedCentralPubMed

51.

Raz N, Ghisletta P, Rodrigue KM, Kennedy KM, Lindenberger U. Trajectories of brain aging in middle-aged and older adults: regional and individual differences. Neuroimage. 2010;51:501–11.PubMedCentralPubMed

52.

Longstreth Jr WT, Manolio TA, Arnold A, Burke GL, Bryan N, Jungreis CA, et al. Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3301 elderly people. The Cardiovascular Health Study. Stroke. 1996;27:1274–82.PubMed

53.

Meier IB, Manly JJ, Provenzano FA, Louie KS, Wasserman BT, Griffith EY, et al. White matter predictors of cognitive functioning in older adults. J Int Neuropsychol Soc. 2012;18:414–27.PubMedCentralPubMed

54.

Resnick SM, Pham DL, Kraut MA, Zonderman AB, Davatzikos C. Longitudinal magnetic resonance imaging studies of older adults: a shrinking brain. J Neurosci. 2003;23:3295–301.PubMed

55.

Pfefferbaum A, Sullivan EV, Hedehus M, Lim KO, Adalsteinsson E, Moseley M. Age-related decline in brain white matter anisotropy measured with spatially corrected echo-planar diffusion tensor imaging. Magn Reson Med. 2000;44:259–68.PubMed

56.

Grieve SM, Williams LM, Paul RH, Clark CR, Gordon E. Cognitive aging, executive function, and fractional anisotropy: a diffusion tensor MR imaging study. AJNR Am J Neuroradiol. 2007;28:226–35.PubMed

57.

Haga KK, Khor YP, Farrall A, Wardlaw JM. A systematic review of brain metabolite changes, measured with 1H magnetic resonance spectroscopy, in healthy aging. Neurobiol Aging. 2009;30:353–63.PubMed

58.

Loessner A, Alavi A, Lewandrowski KU, Mozley D, Souder E, Gur RE. Regional cerebral function determined by FDG-PET in healthy volunteers: normal patterns and changes with age. J Nucl Med. 1995;36:1141–9.PubMed

59.

Ott BR, Cohen RA, Gongvatana A, Okonkwo OC, Johanson CE, Stopa EG, et al. Brain ventricular volume and cerebrospinal fluid biomarkers of Alzheimer’s disease. J Alzheimers Dis. 2010;20:647–57.PubMedCentralPubMed

60.

Brickman AM. Contemplating Alzheimer’s disease and the contribution of white matter hyperintensities. Curr Neurol Neurosci Rep. 2013;13:415.PubMed

61.

Sexton CE, Kalu UG, Filippini N, Mackay CE, Ebmeier KP. A meta-analysis of diffusion tensor imaging in mild cognitive impairment and Alzheimer’s disease. Neurobiol Aging. 2011;32:2322. e2325-2318.PubMed

62.

Frings L, Yew B, Flanagan E, Lam BY, Hull M, Huppertz HJ, et al. Longitudinal grey and white matter changes in frontotemporal dementia and Alzheimer’s disease. PLoS One. 2014;9:e90814.PubMedCentralPubMed

63.

Stout JC, Ellis RJ, Jernigan TL, Archibald SL, Abramson I, Wolfson T, et al. Progressive cerebral volume loss in human immunodeficiency virus infection: a longitudinal volumetric magnetic resonance imaging study. HIV Neurobehavioral Research Center Group. Arch Neurol. 1998;55:161–8.PubMed

64.

Zhang N, Song X, Bartha R, Beyea S, D’Arcy R, Zhang Y, et al. Advances in High-Field Magnetic Resonance Spectroscopy in Alzheimer’s Disease. Curr Alzheimer Res. 2014;11:367–88.PubMedCentralPubMed

65.

Adriaanse SM, van Dijk KR, Ossenkoppele R, Reuter M, Tolboom N, Zwan MD, et al. The effect of amyloid pathology and glucose metabolism on cortical volume loss over time in Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2014;41:1190–8.PubMed

66.

Mosconi L, Berti V, Glodzik L, Pupi A, De Santi S, de Leon MJ. Pre-clinical detection of Alzheimer’s disease using FDG-PET, with or without amyloid imaging. J Alzheimers Dis. 2010;20:843–54.PubMedCentralPubMed

67.

Masliah E, DeTeresa RM, Mallory ME, Hansen LA. Changes in pathological findings at autopsy in AIDS cases for the last 15 years. AIDS. 2000;14:69–74.PubMed

68.

Cysique LA, Brew BJ, Halman M, Catalan J, Sacktor N, Price RW, et al. Undetectable cerebrospinal fluid HIV RNA and beta-2 microglobulin do not indicate inactive AIDS dementia complex in highly active antiretroviral therapy-treated patients. J Acquir Immune Defic Syndr. 2005;39:426–9.PubMed

69.

Gongvatana A, Harezlak J, Buchthal S, Daar E, Schifitto G, Campbell T, et al. Progressive cerebral injury in the setting of chronic HIV infection and antiretroviral therapy. J Neurovirol. 2013;19:209–18.PubMedCentralPubMed

70.

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;19:407–11.PubMed

71.

Brew BJ, Crowe SM, Landay A, Cysique LA, Guillemin G. Neurodegeneration and ageing in the HAART era. J Neuroimmune Pharmacol. 2009;4:163–74.PubMed

72.

Ortega M, Ances BM. Role of HIV in amyloid metabolism. J Neuroimmune Pharmacol. 2014;9:483–91.PubMedCentralPubMed

73.

Everall I, Vaida F, Khanlou N, Lazzaretto D, Achim C, Letendre S, et al. Cliniconeuropathologic correlates of human immunodeficiency virus in the era of antiretroviral therapy. J Neurovirol. 2009;15:360–70.PubMedCentralPubMed

74.

Braak H, Alafuzoff I, Arzberger T, Kretzschmar H, Del Tredici K. Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol. 2006;112:389–404.PubMedCentralPubMed

75.

Nebuloni M, Pellegrinelli A, Ferri A, Bonetto S, Boldorini R, Vago L, et al. Beta amyloid precursor protein and patterns of HIV p24 immunohistochemistry in different brain areas of AIDS patients. AIDS. 2001;15:571–5.PubMed

76.

Fjell AM, McEvoy L, Holland D, Dale AM, Walhovd KB. What is normal in normal aging? Effects of aging, amyloid and Alzheimer’s disease on the cerebral cortex and the hippocampus. Prog Neurobiol. 2014;117:20–40.PubMed

77.

Piccini A, Russo C, Gliozzi A, Relini A, Vitali A, Borghi R, et al. beta-amyloid is different in normal aging and in Alzheimer disease. J Biol Chem. 2005;280:34186–92.PubMed

78.

Anthony IC, Ramage SN, Carnie FW, Simmonds P, Bell JE. 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. 2006;111:529–38.PubMed

79.

Smith DB, Simmonds P, Bell JE. Brain viral burden, neuroinflammation and neurodegeneration in HAART-treated HIV positive injecting drug users. J Neurovirol. 2014;20:28–38.PubMed

80.

Becker JT, Kingsley L, Mullen J, Cohen B, Martin E, Miller EN, et al. Vascular risk factors, HIV serostatus, and cognitive dysfunction in gay and bisexual men. Neurology. 2009;73:1292–9.PubMedCentralPubMed

81.

Price JL, Davis PB, Morris JC, White DL. The distribution of tangles, plaques and related immunohistochemical markers in healthy aging and Alzheimer’s disease. Neurobiol Aging. 1991;12:295–312.PubMed

82.

Brew BJ, Pemberton L, Blennow K, Wallin A, Hagberg L. CSF amyloid beta42 and tau levels correlate with AIDS dementia complex. Neurology. 2005;65:1490–2.PubMed

83.

Gisslen M, Krut J, Andreasson U, Blennow K, Cinque P, Brew BJ, et al. Amyloid and tau cerebrospinal fluid biomarkers in HIV infection. BMC Neurol. 2009;9:63.PubMedCentralPubMed

84.

Marra CM, Zhao Y, Clifford DB, Letendre S, Evans S, Henry K, et al. Impact of combination antiretroviral therapy on cerebrospinal fluid HIV RNA and neurocognitive performance. AIDS. 2009;23:1359–66.PubMedCentralPubMed

85.

Peluso MJ, Meyerhoff DJ, Price RW, Peterson J, Lee E, Young AC, et al. Cerebrospinal fluid and neuroimaging biomarker abnormalities suggest early neurological injury in a subset of individuals during primary HIV infection. J Infect Dis. 2013;207:1703–12.PubMedCentralPubMed

86.

Banks WA, Ercal N, Price TO. The blood–brain barrier in neuroAIDS. Curr HIV Res. 2006;4:259–66.PubMed

87.

Anderson E, Zink W, Xiong H, Gendelman HE. HIV-1-associated dementia: a metabolic encephalopathy perpetrated by virus-infected and immune-competent mononuclear phagocytes. J Acquir Immune Defic Syndr. 2002;31:S43–54.PubMed

88.

Andras IE, Toborek M. Amyloid beta accumulation in HIV-1-infected brain: the role of the blood brain barrier. IUBMB Life. 2013;65:43–9.PubMedCentralPubMed

89.

Andras IE, Eum SY, Huang W, Zhong Y, Hennig B, Toborek M. HIV-1-induced amyloid beta accumulation in brain endothelial cells is attenuated by simvastatin. Mol Cell Neurosci. 2010;43:232–43.PubMedCentralPubMed

90.

Erickson MA, Banks WA. Blood–brain barrier dysfunction as a cause and consequence of Alzheimer’s disease. J Cereb Blood Flow Metab. 2013;33:1500–13.PubMedCentralPubMed

91.

Raber J, Huang Y, Ashford JW. ApoE genotype accounts for the vast majority of AD risk and AD pathology. Neurobiol Aging. 2004;25:641–50.PubMed

92.

Chang L, Andres M, Sadino J, Jiang CS, Nakama H, Miller E, et al. Impact of apolipoprotein E epsilon4 and HIV on cognition and brain atrophy: antagonistic pleiotropy and premature brain aging. Neuroimage. 2011;58:1017–27.PubMedCentralPubMed

93.

Burt TD, Agan BK, Marconi VC, He W, Kulkarni H, Mold JE, et al. Apolipoprotein (apo) E4 enhances HIV-1 cell entry in vitro, and the APOE epsilon4/epsilon4 genotype accelerates HIV disease progression. Proc Natl Acad Sci U S A. 2008;105:8718–23.PubMedCentralPubMed

94.

Morgan EE, Woods SP, Letendre SL, Franklin DR, Bloss C, Goate A, et al. Apolipoprotein E4 genotype does not increase risk of HIV-associated neurocognitive disorders. J Neurovirol. 2013;19:150–6.PubMedCentralPubMed

95.

Desplats P, Dumaop W, Smith D, Adame A, Everall I, Letendre S, et al. Molecular and pathologic insights from latent HIV-1 infection in the human brain. Neurology. 2013;80:1415–23.PubMedCentralPubMed

96.

Minghetti L, Visentin S, Patrizio M, Franchini L, Ajmone-Cat MA, Levi G. Multiple actions of the human immunodeficiency virus type-1 Tat protein on microglial cell functions. Neurochem Res. 2004;29:965–78.PubMed

97.

Mollace V, Nottet HS, Clayette P, Turco MC, Muscoli C, Salvemini D, et al. Oxidative stress and neuroAIDS: triggers, modulators and novel antioxidants. Trends Neurosci. 2001;24:411–6.PubMed

98.

Harman D, Hendricks S, Eddy DE, Seibold J. Free radical theory of aging: effect of dietary fat on central nervous system function. J Am Geriatr Soc. 1976;24:301–7.PubMed

99.

Mattson MP, Haughey NJ, Nath A. Cell death in HIV dementia. Cell Death Differ. 2005;12:893–904.PubMed

100.

Tian C, Sun L, Jia B, Ma K, Curthoys N, Ding J, et al. Mitochondrial glutaminase release contributes to glutamate-mediated neurotoxicity during human immunodeficiency virus-1 infection. J Neuroimmune Pharmacol. 2012;7:619–28.PubMedCentralPubMed

101.

Shi Q, Gibson GE. Oxidative stress and transcriptional regulation in Alzheimer disease. Alzheimer Dis Assoc Disord. 2007;21:276–91.PubMedCentralPubMed

102.

Nakamura T, Watanabe A, Fujino T, Hosono T, Michikawa M. Apolipoprotein E4 (1–272) fragment is associated with mitochondrial proteins and affects mitochondrial function in neuronal cells. Mol Neurodegener. 2009;4:35.PubMedCentralPubMed

103.

Garvey LJ, Pavese N, Politis M, Ramlackhansingh A, Brooks DJ, Taylor-Robinson SD, et al. Increased microglia activation in neurologically asymptomatic HIV-infected patients receiving effective ART. AIDS. 2014;28:67–72.PubMed

104.

Zhang Y, Wang M, Li H, Zhang H, Shi Y, Wei F, et al. Accumulation of nuclear and mitochondrial DNA damage in the frontal cortex cells of patients with HIV-associated neurocognitive disorders. Brain Res. 2012;1458:1–11.PubMed

105.

Coughlin JM, Wang Y, Ma S, Yue C, Kim PK, Adams AV, et al. Regional brain distribution of translocator protein using [C]DPA-713 PET in individuals infected with HIV. J Neurovirol. 2014;20:219–32.PubMedCentralPubMed

106.

Edison P, Archer HA, Gerhard A, Hinz R, Pavese N, Turkheimer FE, et al. Microglia, amyloid, and cognition in Alzheimer’s disease: an [11C](R)PK11195-PET and [11C]PIB-PET study. Neurobiol Dis. 2008;32:412–9.PubMed

107.

Kim J, Yoon JH, Kim YS. HIV-1 Tat interacts with and regulates the localization and processing of amyloid precursor protein. PLoS One. 2013;8:e77972.PubMedCentralPubMed

108.

Wojda U, Salinska E, Kuznicki J. Calcium ions in neuronal degeneration. IUBMB Life. 2008;60:575–90.PubMed

109.

Vidal F, Gutierrez F, Gutierrez M, Olona M, Sanchez V, Mateo G, et al. Pharmacogenetics of adverse effects due to antiretroviral drugs. AIDS Rev. 2010;12:15–30.PubMed

110.

Letendre SL, McCutchan JA, Childers ME, Woods SP, Lazzaretto D, Heaton RK, et al. Enhancing antiretroviral therapy for human immunodeficiency virus cognitive disorders. Ann Neurol. 2004;56:416–23.PubMed

111.

Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, Rao S, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med. 2006;12:1365–71.PubMed

112.

Lyn-Cook Jr LE, Lawton M, Tong M, Silbermann E, Longato L, Jiao P, et al. Hepatic ceramide may mediate brain insulin resistance and neurodegeneration in type 2 diabetes and non-alcoholic steatohepatitis. J Alzheimers Dis. 2009;16:715–29.PubMedCentralPubMed

113.

Grassi MP, Clerici F, Perin C, Zocchetti C, Borella M, Cargnel A, et al. HIV infection and drug use: influence on cognitive function. AIDS. 1995;9:165–70.PubMed

114.

Nix LM, Tien PC. Metabolic syndrome, diabetes, and cardiovascular risk in HIV. Curr HIV/AIDS Rep. 2014;11:271–8.PubMed

115.

El-Sadr WM, Mullin CM, Carr A, Gibert C, Rappoport C, Visnegarwala F, et al. Effects of HIV disease on lipid, glucose and insulin levels: results from a large antiretroviral-naive cohort. HIV Med. 2005;6:114–21.PubMed

116.

S Roriz-Filho J, Sá-Roriz TM, Rosset I, Camozzato AL, Santos AC, Chaves ML, et al. (Pre)diabetes, brain aging, and cognition. Biochim Biophys Acta. 2009;1792:432–43.PubMed

117.

Yaffe K. Metabolic syndrome and cognitive disorders: is the sum greater than its parts? Alzheimer Dis Assoc Disord. 2007;21:167–71.PubMed

118.

Cohen RA, Poppas A, Forman DE, Hoth KF, Haley AP, Gunstad J, et al. Vascular and cognitive functions associated with cardiovascular disease in the elderly. J Clin Exp Neuropsychol. 2009;31:96–110.PubMedCentralPubMed

119.

Correia SC, Santos RX, Carvalho C, Cardoso S, Candeias E, Santos MS, et al. Insulin signaling, glucose metabolism and mitochondria: major players in Alzheimer’s disease and diabetes interrelation. Brain Res. 2012;1441:64–78.PubMed

120.

Izycka-Swieszewska E, Zoltowska A, Rzepko R, Gross M, Borowska-Lehman J. Vasculopathy and amyloid beta reactivity in brains of patients with acquired immune deficiency (AIDS). Folia Neuropathol. 2000;38:175–82.PubMed

121.

Nelson L, Gard P, Tabet N. Hypertension and inflammation in Alzheimer’s disease: close partners in disease development and progression! J Alzheimers Dis. 2014;41:331–43.PubMed

Title: HIV effects on age-associated neurocognitive dysfunction: premature cognitive aging or neurodegenerative disease?
Authors: Ronald A Cohen
Talia R Seider
Bradford Navia
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Alzheimer's Research & Therapy / Issue 1/2015
Electronic ISSN: 1758-9193
DOI: https://doi.org/10.1186/s13195-015-0123-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

HIV effects on age-associated neurocognitive dysfunction: premature cognitive aging or neurodegenerative disease?

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2015

Central delivery of iodine-125–labeled cetuximab, etanercept and anakinra after perispinal injection in rats: possible implications for treating Alzheimer’s disease

Long-term donepezil use for dementia with Lewy bodies: results from an open-label extension of Phase III trial

Clinical and imaging features of mixed Alzheimer and vascular pathologies

Mild cognitive impairment and deficits in instrumental activities of daily living: a systematic review

Co-morbidity and systemic inflammation as drivers of cognitive decline: new experimental models adopting a broader paradigm in dementia research

Brivaracetam, but not ethosuximide, reverses memory impairments in an Alzheimer’s disease mouse model