Skip to main content
SpringerLink
Log in

The AIDS dementia complex: Clinical and basic Neuroscience with implications for novel molecular therapies

  • Part I HIV-1 Asociated Dementia (HAD)
  • Published:
Neurotoxicity Research Aims and scope Submit manuscript

Abstract

The AIDS dementia complex (ADC, also referred to as HIV-associated cognitive impairment) is a common disorder among HIV-infected patients associated with both inflammatory and neurodegenerative processes. This review describes recent advances in the clinical and basic neurosciences of HIV infection and discusses the multivariable nature of what has become a chronic disorder in the context of highly active antiretroviral therapies (HAART). Since its initial description twenty years ago, advances in cell and molecular biology along with those in neuroimaging have furthered our understanding of the underlying pathogenic mechanisms. The clinical and neuropsychological profile of ADC is generally consistent with a “frontal-subcortical” pattern of injury. Neuropathogenesis is largely driven by indirect mechanisms mediated by infected, or more commonly, immune activated macrophages, which secrete viral and host-derived factors. Magnetic resonance spectroscopy (MRS) provides a robustin vivo method to measure the inflammatory and neurotoxic events triggered by these factors and their associated signals. Although the use of HAART has significantly improved survival rates, cerebral injury and cognitive impairment remain common events. Factors such as aging and chronic infection will likely impact the course of this disease, its pathogenesis, and treatment. The combined observations presented in this review suggest a number of critical areas for future inquiry.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Adamson DC, B Wildemann, M Sasaki, JD Glass, JC McArthur, VI Christov, TM Dawson and VL Dawson (1996) Immunologic NO synthase: elevation in severe AIDS dementia and induction by HIV-1 gp 41.Science 27, 1917–1920.

    Article  Google Scholar 

  • Albert SM, K Marder, G Dooneief, K Bell, M Sano, G Todak and Y Stern (1995) Neuropsychologic impairment in early HIV infection. A risk factor for work disability.Arch. Neurol. 52(5), 525–530.

    PubMed  CAS  Google Scholar 

  • Albright AV, JT Shieh, T Itoh, B Lee, D Pleasure, MJ O’Connor, RW Doms and F Gonzalez-Scarano (1999) Microglia express CCR5, CXCR4, and CCR3, but of these, CCR5 is the principal coreceptor for human immunodeficiency virus type 1 dementia isolates.J. Virol. 73, 205–213.

    PubMed  CAS  Google Scholar 

  • Anderson ER, J Boyle, WE Zink, Y Persidsky, HE Gendelman and H Xiong (2003) Hippocampal synaptic dysfunction in a murine model of human immunodeficiency virus type 1 encephalitis.Neuroscience 118, 359–369.

    Article  PubMed  CAS  Google Scholar 

  • Anderson ER, HE Gendelman and H Xiong (2004) Memantine protects hippocampal neuronal function in murine human immuno-deficiency virus type 1 encephalitis.J. Neurosci. 24, 7194–7198.

    Article  PubMed  CAS  Google Scholar 

  • Asensio VC, J Maier, R Milner, K Boztug, C Kincaid, M Moulard, C Phillipson, K Lindsley, T Krucker, HS Fox and IL Campbell (2001) Interferon-independent, human immunodeficiency virus type 1 gp120-mediated induction of CXCL10/IP-10 gene expression by astrocytesin vivo andin vitro.J Virol. 75(15), 7067–7077.

    Article  PubMed  CAS  Google Scholar 

  • Aylward EH, JD Henderer, JC McArthur, PD Brettschneider, GJ Harris, PE Barta and GD Pearlson (1993) Reduced basal ganglia volume in HIV-1-associated dementia: results from quantitative neuroimaging.Neurology 43, 2099–2104.

    PubMed  CAS  Google Scholar 

  • Barker PB, RR Lee and JC McArthur (1995) AIDS dementia complex: evaluation with proton MR spectroscopic imaging.Radiology 195, 58–64.

    PubMed  CAS  Google Scholar 

  • Bezzi P, M Domercq, L Brambilla, R Galli, D Schols, E De Clercq, A Vescovi, G Bagetta, G Kollias, J Meldolesi and A Volterra (2001) CXCR4-activated astrocyte glutamate release via TNF-alpha: amplification by microglia triggers neurotoxicity.Nat. Neurosci. 4, 702–710.

    Article  PubMed  CAS  Google Scholar 

  • Brew BJ, RB Bhalla, M Paul, JJ Sidtis, JJ Keilp, AE Sadler, H Gallardo, JC McArthur, MK Schwartz and RW Price (1992) Cerebrospinal fluid 2 microglobulin in patients with AIDS dementia complex: an expanded series, including response to zidovudine treatment.AIDS 6, 461–465.

    Article  PubMed  CAS  Google Scholar 

  • Brew BJ, L Pemberton, P Cunningham and MG Law (1997) Levels of human immunodeficiency virus type 1 RNA in cerebrospinal fluid correlate with AIDS dementia stage.J. Infect. Dis. 175, 963–966.

    Article  PubMed  CAS  Google Scholar 

  • Brew BJ, RB Bhalla, M Paul, H Gallardo, JC McArthur, MK Schwartz and RW Price (1998) Cerebrospinal fluid neopterin in human immunodefiency virus type 1 infection.Ann. Neurol. 28, 556–560.

    Article  Google Scholar 

  • Brines ML, P Ghezzi, S Keenan, D Agnello, NC de Lanerolle, C Cerami, LM Itri and A Cerami (2000) Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury.Proc. Natl. Acad. Sci. USA 97, 10526–10531.

    Article  PubMed  CAS  Google Scholar 

  • Brodt HR, BS Kamps, P Gute, B Knupp, S Staszewski and EB Helm (1997) Changing incidence of AIDS-defining illnesses in the era of antiretroviral combination therapy.AIDS 11, 1731–1738.

    Article  PubMed  CAS  Google Scholar 

  • Budka H, CA Wiley, P Kleihues, J Artigas, AK Asbury, ES Cho, DR Cornblath, MC Dal Canto, U DeGirolami, D Dickson, LG Epstein, MM Esiri, F Giangaspero, G Gosztonyi, F Gray, JW Griffin, D Henin, Y Iwasaaki, RS Janssen, RT Johnson, PL Lantos, WD Lyman, JC McArthur, K Nagashima, N Peress, CK Petito, RW Price, RH Rhodes, M Rosenblum, G Said, F Scaravilli, LR Sharer and HV Vinters (1991) HIV-associated disease of the nervous system: review of nomenclature and proposal for neuropathology-based terminology.Brain Pathol. 1, 143–152.

    Article  PubMed  CAS  Google Scholar 

  • Burger DM, CL Kraaijeveld, PL Meenhorst, JW Mulder, CH Koks, A Bult and JH Beijnen (1993) Penetration of zidovudine into the cerebrospinal fluid of patients infected with HIV.AIDS 7, 1581–1587.

    Article  PubMed  CAS  Google Scholar 

  • Chang L, T Ernst, MD Witt, N Ames, I Walot, J Jovicich, M DeSilva, N Trivedi, O Speck and EN Miller (2003) Persistent brain abnormalities in antiretroviral-naive HIV patients 3 months after HAART.Antivir. Ther. 8, 17–26.

    PubMed  CAS  Google Scholar 

  • Chang L, PL Lee, CT Yiannoutsos,T Ernst, CM Marra, T Richards, D Kolson, G Schifitto, JG Jarvik, EN Miller, R Lenkinski, G Gonzalez, B A Navia and HIV MRS Consortium (2004) A multi-centerin vivo proton MRS study of HIV-associated dementia and its relationship to aging.NeuroImage 23, 1136–1347.

    Article  Google Scholar 

  • Chen P, M Mayne, C Power and A Nath (1997) The tat protein of HIV-1 induces tumor necrosis factor-alpha production. Implications for HIV-1-associated neurological diseases.J. Biol. Chem. 272, 22385–22388.

    Article  PubMed  CAS  Google Scholar 

  • Cherner M, RJ Ellis, D Lazzaretto, C Young, MR Mindt, JH Atkinson, I Grant, RK Heaton and the HNRC Group (2004) Effects of HIV-1 infection and aging on neurobehavioral functioning: preliminary findings.AIDS 18(suppl. 1), S27-S34.

    PubMed  Google Scholar 

  • Cherner M, SL Letendre, RK Heaton, J Durelle, J Marquie-Beck, B Gragg, I Grant and the HNRC Group (2005) Hepatitis C augments cognitive deficits associated with HIV infection and methamphetamine.Neurology 64, 1343–1347.

    PubMed  CAS  Google Scholar 

  • Childs EA, RH Lyles, OA Selnes, B Chen, EN Miller, BA Cohen, JT Becker, J Mellors and JC McArthur (1999) Plasma viral load and CD4 lymphocytes predict HIV-associated dementia and sensory neuropathy.Neurology 52, 607–613.

    PubMed  CAS  Google Scholar 

  • Chong WK, M Paley, ID Wilkinson, MA Hall-Craggs, B Sweeney, MJ Harrison, RF Miller and BE Kendall (1994) Localized cerebral proton MR spectroscopy in HIV infection and AIDS.Am. J. Neuroradiol. 15, 21–25.

    PubMed  CAS  Google Scholar 

  • Cinque P, L Vago, M Mengozzi, V Torri, D Ceresa, E Vicenzi, P Transidico, A Vagani, S Sozzani, A Mantovani, A Lazzarin and G Poli (1998) Elevated cerebrospinal fluid levels of monocyte chemotactic protein-1 correlate with HIV-1 encephalitis and local viral replication.AIDS 12, 1327–1332.

    PubMed  CAS  Google Scholar 

  • Cohen R, R Paul, T Flanigan and BA Navia (2004) Age-related HIV neurocognitive dysfunction.Neurology.

  • Conant K, A Garzino-Demo, A Nath, JC McArthur, W Halliday, C Power, RC Gallo and EO Major (1998) Induction of monocyte chemoattractant protein-1 in HIV-1 tat-stimulated astrocytes and elevation in AIDS dementia.Proc. Natl. Acad. Sci. USA 5 (6), 3117–3121.

    Article  Google Scholar 

  • Cunningham PH, DG Smith, C Satchell, DA Cooper and B Brew (2000) Evidence for independent development of resistance to HIV reverse transcriptase inhibitors in the cerebropsinal fluid.AIDS 14, 1949–1954.

    Article  PubMed  CAS  Google Scholar 

  • Dal Pan GJ, H Farzadegan, O Selnes, DR Hoover, EN Miller, RL Skolasky, TE Nance-Sproson and JC McArthur (1998) Sustained cognitive decline in HIV infection: relationship to CD4+ cell count, plasma viremia and p24 antigenemia.J. Neurovirol. 4, 95–99.

    Google Scholar 

  • De Luca A, BC Ciancio, D Larussa, R Murri, A Cingolani, MG Rizzo, ML Giancola, A Ammassari and L Ortona (2002) Correlates of independent HIV-1 replication in the CNS and of its control by antiretrovirals.Neurology 59, 342–347.

    PubMed  Google Scholar 

  • Deutsch R, RJ Ellis, A McCutchan, TD Marcotte, S Letendre, I Grant and the HNRC Group. (2001) AIDS-associated mild neurocognitive impairment is delayed in the era of highly active antiretroviral therapy (HAART).AIDS 15, 1898–1899.

    Article  PubMed  CAS  Google Scholar 

  • Digicaylioglu M and SA Lipton (2001) Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NFΚB signalling cascades.Nature 412, 641–647.

    Article  PubMed  CAS  Google Scholar 

  • Digicaylioglu M, M Kaul, L Fletcher, R Dowen and SA Lipton (2004) Erythropoietin protects cerebrocortical neurons from HIV-1/gp120-induced damage.NeuroReport 15, 761–763.

    Article  PubMed  Google Scholar 

  • Di Stefano M, S Wilt, F Gray, M Dubois-Dalcq and F Chiodi (1996) HIV type 1 V3 sequences and the development of dementia during AIDS.AIDS Res. Hum. Retrovir. 12, 471–476.

    PubMed  Google Scholar 

  • Dore GJ, PK Correll, Y Li, JM Kaldor, DA Cooper and BJ Brew (1999) Changes to AIDS dementia complex in the era of highly active antiretroviral therapy.AIDS 13, 1249–1253.

    Article  PubMed  CAS  Google Scholar 

  • Dreyer EB, PK Kaiser, JT Offermann and SA Lipton (1990) HIV-1 coat protein neurotoxicity prevented by a calcium channel antagonists.Science 248, 364–367.

    Article  PubMed  CAS  Google Scholar 

  • Ellis RJ, K Hsia, SA Spector, JA Nelson, RK Heaton, MR Wallace, I Abramson, JH Atkinson, I Grant and JA McCutchan (1997) Cerebrospinal fluid human immunodeficiency virus type 1 RNA levels are elevated in neurocognitively impaired individuals with acquired immunodeficiency syndrome. HIV Neurobehavioral Research Center Group.Ann. Neurol. 42, 679–688.

    Article  PubMed  CAS  Google Scholar 

  • Ellis RJ, JA McCutchan, RK Heatonet al. (1999). Elevated HIV RNA Levels in cerebrospinal fluid predict increased subsequent risk for the development of neurocognitive disorders.Neurology. 52, A253.

    Article  Google Scholar 

  • Enting RH, RM Hoetelmans, JM Lange, DM Burger, JH Beijnen and P Portegies (1998) Antiretroviral drugs and the central nervous system.AIDS 12, 1941–1955.

    Article  PubMed  CAS  Google Scholar 

  • Erichsen D, AL Lopez, H Peng, D Niemann, C Williams, M Bauer, S Morgello, RL Cotter, LA Ryan, A Ghorpade, HE Gendelman and J Zheng (2003) Neuronal injury regulates fractalkine: relevance for HIV-1 associated dementia.J. Neuroimmunol. 138, 144–155.

    Article  PubMed  CAS  Google Scholar 

  • Everall IP, PJ Luthert and PL Lantos (1993) A review of neuronal damage in human immunodeficiency virus infection: its assessment, possible mechanism and relationship to dementia.J. Neuropathol. Exp. Neurol. 52, 561–566.

    Article  PubMed  CAS  Google Scholar 

  • Everall IP, RK Heaton, TD Marcotte, RJ Ellis, JA McCutchan, JH Atkinson, I Grant, M Mallory and E Masliah (1999) Cortical synaptic density is reduced in mild to moderate human immuno-deficiency virus neurocognitive disorder. HNRC Group. HIV Neurobehavioral Research Center.Brain Pathol. 9, 209–217.

    PubMed  CAS  Google Scholar 

  • Ferrando S, W van Gorp, M McElhiney, K Goggin, M Sewell and J Rabkin (1998) Highly active antiretroviral treatment in HIV infection: benefits for neuropsychological function.AIDS 12, F65-F70.

    Article  PubMed  CAS  Google Scholar 

  • Filippi CG, AM Ulug, E Ryan, SJ Ferrando and W van Gorp (2001) Diffusion tensor imaging of patients with HIV and normal-appearing white matter on MR images of the brain.Am. J. Neuroradiol. 22, 277–283.

    PubMed  CAS  Google Scholar 

  • Foudraine NA, RM Hoetelmans, JM Lange, F de Wolf, BH van Benthem, JJ Maas, IP Keet and P Portegies (1998) Cerebrospinal-fluid HIV-1 RNA and drug concentrations after treatment with lamivudine plus zidovudine or stavudine.Lancet 351 (9115), 1547–1551.

    Article  PubMed  CAS  Google Scholar 

  • Gartner S and y Liu (2002). Insights into the role of immune activation in HIV neuropathogenesis.J. Neurovirol. 8, 69–75.

    Article  PubMed  CAS  Google Scholar 

  • Gelbard HA, HS Nottet, S Swindells, M Jett, KA Dzenko, P Genis, R White, L Wang, YB Choi and D Zhang (1994) Platelet-Activity Factor: A candidate human immunodeficiency virus type 1-induced neurotoxin.J. Virol. 68, 4628–4635.

    PubMed  CAS  Google Scholar 

  • Gisolf EH, RM van Praag, S Jurriaans, P Portegies, J Goudsmit, SA Danner, JM Lange and JM Prins (2000) Increasing cerebrospinal fluid chemokine concentrations despite undetectable cerebrospinal fluid HIV RNA in HIV-1-infected patients receiving antiretroviral therapy.J. Acquir. Immune Defic. Syndr. 25, 426–433.

    Article  PubMed  CAS  Google Scholar 

  • Gisslen M, G Norkrans, B Svennerholm and L Hagberg (1997) The effect on human immunodeficiency virus type 1 RNA levels in cerebrospinal fluid after initiation of zidovudine or didanosine.J. Infect. Dis. 175, 434–437.

    PubMed  CAS  Google Scholar 

  • Giulian D, K Vaca and CA Noonan (1990) Secretion of neurotoxins of mononuclear phagocytes infected with HIV-1.Science 250, 1593–1596.

    Article  PubMed  CAS  Google Scholar 

  • Glass JD, SL Wesselingh, OA Selnes and JC McArthur (1993) Clinical-neuropathologic correlation in HIV-associated dementia.Neurology 43, 2230–2237.

    PubMed  CAS  Google Scholar 

  • Gonzalez E, BH Rovin, L Sen, G Cooke, R Dhanda, S Mummidi, H Kulkarni, MJ Bamshad, V Telles, SA Anderson, EA Walter, KT Stephan, M Deucher, A Mangano, R Bologna, SS Ahuja, MJ Dolan and SK Ahuja (2002) HIV-1 infection and AIDS dementia are influenced by a mutant MCP-1 allele linked to increased monocyte infiltration of tissues and MCP-1 levels.Proc. Natl. Acad. Sci. USA 99 (21), 13795–13800.

    Article  PubMed  CAS  Google Scholar 

  • Grant I, JH Atkinson, JR Hesselink, CJ Kennedy, DD Richman, SA Spector and JA McCutchan (1987) Evidence for early central nervous system involvement in AIDS.Ann. Int. Med. 107, 828–836

    PubMed  CAS  Google Scholar 

  • Gulick RM, JW Mellors, D Havlir, JJ Eron, C Gonzalez, D McMahon, DD Richman, FT Valentine, L Jonas, A Meibohm, EA Emini and JA Chodakewitz (1997) Treatment with indinavir, zidovudine, and lamivudine in adults with human immuno-deficiency virus infection and prior antiretroviral therapy.N. Engl. J. Med. 337 (11), 734–739.

    Article  PubMed  CAS  Google Scholar 

  • Hammer SM, KE Squires, MD Hughes, JM Grimes, LM Demeter, JS Currier, JJ Eron Jr, JE Feinberg, HH Balfour Jr, LR Deyton, JA Chodakewitz and MA Fischl (1997) A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team.N. Engl. J. Med. 337 (11), 725–733.

    Article  PubMed  CAS  Google Scholar 

  • He J, Y Chen, M Farzan, H Choe, A Ohagen, S Gartner, J Busciglio, X Yang, W Hofmann, W Newman, CR Mackay, J Sodroski and D Gabuzda (1997) CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia.Nature 385 (6617), 645–649.

    Article  PubMed  CAS  Google Scholar 

  • Heaton RK, I Grant, N Butters, DA White, D Kirson, JH Atkinson, JA McCutchan, MJ Taylor, MD Kelly, RJ Ellis, T Wolfson, R Velin, TD Marcotte, JF Hesselink, TLL Jernigan, J Chandler, M Wallace, I Abramson and HNRC Group (1995) The HNRC 500--neuropsychology of HIV infection at different disease stages. HIV Neurobehavioral Research Center.J. Int. Neuropsychol. Soc. 1, 231–251. Heckmann JG, C Kayser, D Heuss, B Manger, HE Blum and B Neundorfer (1999) Neurological manifestations of chronic hepatitis C.Neurology 246, 486-491.

    Article  PubMed  CAS  Google Scholar 

  • Hesselgesser J, D Taub, P Baskar, M Greenberg, J Hoxie, DL Kolson and R Horuk (1998) Neuronal apoptosis induced by HIV-1 gp120 and the chemokine SDF-1 alpha is mediated by the chemokine receptor CXCR4.Curr. Biol. 8, 595–598.

    Article  PubMed  CAS  Google Scholar 

  • Heyes MP, BJ Brew, A Martin, RW Price, AM Salazar, JJ Sidtis, JA Yergey, MM Mouradian, AE Sadler, J Keilp, D Rubinow and S Markey (1991) Quinolinic acid in cerebrospinal fluid and serum in HIV-1 infection: relationship to clinical and neurological status.Ann. Neurol. 29, 202–209.

    Article  PubMed  CAS  Google Scholar 

  • Hsu H, J Xiong and DV Goeddel (1995) The TNF receptor-1 associated protein TRADD signals cell death and NFΚB activation.Cell 81, 495–504.

    Article  PubMed  CAS  Google Scholar 

  • Jarvik JG, RE Lenkinski, AJ Saykin, A Jaans and I Frank (1996) Proton spectroscopy in asymptomatic HIV-infected adults: initial results in a prospective cohort study.J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 13, 247–253.

    PubMed  CAS  Google Scholar 

  • Jernigan TL, S Archibald, JR Hesselink, JH Atkinson, RA Velin, JA McCutchan, J Chandler and I Grant (1993) MRI morphometric analysis of cerebral volume loss in HIV infection.Arch. Neurol. 50, 250–255.

    PubMed  CAS  Google Scholar 

  • Kaul M and SA Lipton (1999) Chemokines and activated macrophages in HIV gp120-induced neuronal apoptosis. Proc. Natl. Acad. Sci. USA 96 (14), p. 8212–8216.

    Article  PubMed  CAS  Google Scholar 

  • Kaul M, GA Garden and SA Lipton (2001) Pathways to neuronal injury and apoptosis in HIV-associated dementia. Nature 410 (6831), 988–994.

    Article  PubMed  CAS  Google Scholar 

  • Kelder W, JC McArthur, T Nance-Sproson, D McClernon and DE Griffin (1998) Beta-chemokines MCP-1 and RANTES are selectively increased in cerebrospinal fluid of patients with human immunodeficiency virus-associated dementia. Ann. Neurol. 44, 831–835.

    Article  PubMed  CAS  Google Scholar 

  • Keswani SC, M Polley, CA Pardo, JW Griffin, JC McArthur and A Hoke (2003) Schwann cell chemokine receptors mediate HIV-1 gp120 toxicity to sensory neurons. Ann. Neurol. 54L 287–296.

    Article  CAS  Google Scholar 

  • Khanna KV, XF Yu, DH Ford, L Ratner, JK Hildreth and RB Markham (2000) Differences among HIV-1 variants in their ability to elicit secretion of TNF-alpha. J. Immunol. 164, 1408–1415.

    PubMed  CAS  Google Scholar 

  • Klein RS, KC Williams, X Alvarez-Hernandez, S Westmoreland, F Force, AA Lackner and AD Luster (1999). Chemokine receptor expression and signaling in macaque and human fetal neurons and astrocytes: implications for the neuropathogenesis of AIDS. J. Immunol. 163, 1636–1646.

    PubMed  CAS  Google Scholar 

  • Kneissl M, K Rostasy, D Goeddel and BA Navia (2005) TRADD is an important intracellular signal that mediates the effects of TNF-[a] in the HIV-1 infected brain (Submitted)

  • Koenig S, H Gendelman, JM Orenstein, MC Dal Canto, GH Pezeshkpour, M Yungbluth, F Janotta, A Aksamit, MA Martin and AS Fauci (1986) Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy. Science 233,1089–1093.

    Article  PubMed  CAS  Google Scholar 

  • Kolb SA, B Sporer, F Lahrtz, U Koedel, HW Pfister and A Fontana (1999) Identification of a T cell chemotactic factor in the cerebrospinal fluid of HIV-1-infected individuals as interferon-gamma inducible protein 10.J. Neuroimmunol. 93, 172–181.

    Article  PubMed  CAS  Google Scholar 

  • Koralnik IJ, A Beaumanoir, R Hausler, A Kohler, AB Safran, R Delacoux, D Vibert, E Mayer, P Burkhard and A Nahory (1990) A controlled study of early neurologic abnormalities in men with asymptomatic HIV infection.N. Engl. J. Med. 232, 864–870.

    Google Scholar 

  • Kusdra L, D McGuire and L Pulliam (2002) Changes in monocyte/macrophage neurotoxicity in the era of HAART: implications for HIV-associated dementia.AIDS 16, 31–38.

    Article  PubMed  CAS  Google Scholar 

  • Kutsch O, J Oh, A Nath and EN Benveniste (2000). Induction of the chemokines interleukin-8 and IP-10 by human immunodeficiency virus type 1 tat in astrocytes.J. Virol. 74, 9214–9221.

    Article  PubMed  CAS  Google Scholar 

  • Langford TD, SL Letendre, TD Marcotte, RJ Ellis, JA McCutchan, I Grant, ME Mallory, LA Hansen, S Archibald, T Jernigan, E Masliah and HNRC Group (2002) Severe, demyelinating leuko-encephalopathy in AIDS patients on antiretroviral therapy.AIDS 16, 1019–1029.

    Article  PubMed  Google Scholar 

  • Lee PL, CT Yiannoutsos, T Ernst, L Chang, CM Marra, JG Jarvik, TL Richards, EW Kwok, DL Kolson, D Simpson, CY Tang, G Schifitto, LM Ketonen, DJ Meyerhoff, RE Lenkinski, RG Gonzalez, BA Navia and the HIV MRS Consortium (2003) A multi-center 1H MRS study of the AIDS dementia complex: validation and preliminary analysis.J. Magn. Reson. Imaging 17, 625–633.

    Article  PubMed  Google Scholar 

  • Letendre SL, ER Lanier and JA McCutchan (1999) Cerebrospinal fluid beta chemokine concentrations in neurocognitively impaired individuals infected with human immunodeficiency virus type 1.J. Infect. Dis. 180, 310–319.

    Article  PubMed  CAS  Google Scholar 

  • Letendre S, J Zheng, C Yiannoutsos, A Lopez, R Ellis, J Marquie-Beck, J Zimmerman, H Gendelman, B Navia and the ACTG301 and 700 Study Teams (2004) Chemokines correlates with cerebral metabolites on magnetic resonance spectroscopy.11th Conference on Retroviruses and Opportunistic Infections. San Fransisco.

  • Lien E, P Aukrust, A Sundan, F Muller, SS Froland and T Espevik (1998) Elevated levels of serum-soluble CD14 in human immunodeficiency virus type 1 (HIV-1) infection: correlation to disease progression and clinical events.Blood 92, 2084–2092.

    PubMed  CAS  Google Scholar 

  • Lipton SA (1992) Memantine prevents HIV coat protein-induced neuronal injuryin vitro. Neurology 42, 1403–1405.

    CAS  Google Scholar 

  • Lipton SA (2004) Failures and successes of NMDA receptor antagonists: molecular basis for the use of open-channel blockers like memantine in the treatment of acute and chronic neurologic insults.NeuroRx 1, 101–110.

    Article  PubMed  Google Scholar 

  • Lipton SA and HE Gendelman (1995) Dementia associated with the acquired immunodeficiency syndrome.N. Engl. J. Med. 16, 934–940.

    Article  Google Scholar 

  • Lopez-Villegas D, RE Lenkinski and I Frank (1997) Biochemical changes in the frontal lobe of HIV-infected individuals detected by magnetic resonance spectroscopy.Proc. Natl. Acad. Sci. USA 94 (18), 9854–9859.

    Article  PubMed  CAS  Google Scholar 

  • Magnuson DSK, BE Knudson, JD Geiger, RM Brownstone and A Nath (1995) Human immunodeficiency virus type 1 tat activates non-N-methyl-D-aspartate excitatory amino acid receptors and causes neurotoxicity.Ann. Neurol. 37, 373–380.

    Article  PubMed  CAS  Google Scholar 

  • Martin EM, DL Pitrak, KJ Pursell, BR Andersen, KM Mullane and RM Novak (1998) Information processing and antiretroviral therapy in HIV-1 infection.J. Int. Neuropsychol. Soc. 4, 329–335.

    PubMed  CAS  Google Scholar 

  • Masliah E, C Achim and N Ge (1992) Spectrum of human immunodeficiency virus-associated neocortical damage.Ann. Neurol. 32, 321–329.

    Article  PubMed  CAS  Google Scholar 

  • Masliah E, RK Heaton, TD Marcotte, RJ Ellis, CA Wiley, M Mallory, CL Achim, JA McCutchan, JA Nelson, JH Atkinson and I Grant (1997) Dendritic injury is a pathological substrate for human immunodeficiency virus-related cognitive disorders. HNRC Group. The HIV Neurobehavioral Research Center.Ann. Neurol. 42, 963–972.

    Article  PubMed  CAS  Google Scholar 

  • Mattson MP, C Culmsee, Z Yu and S Cammadola (2000) Roles of nuclear factor kappaB in neuronal survival and plasticity.J. Neurochem. 74, 443–456.

    Article  PubMed  CAS  Google Scholar 

  • McArthur JC and I Grant (1998) Neurocognitive disorders in HIV infection, In:Neurology of AIDS (Gendelman HEet al., Eds.) (Chapman and Hall).

  • McArthur JC, DR McClernon, MF Cronin, TE Nance-Sproson, AJ Saah, M St Clair and ER Lanier (1997) Relationship between human immunodeficiency virus-associated dementia and viral load in cerebrospinal fluid and brain.Ann. Neurol. 42, 689–698.

    Article  PubMed  CAS  Google Scholar 

  • McArthur JC, E Childs, RH Lyles, E Miller, BA Cohen, BB Chen, J Mellors and JC McArthur (1998) Predictive markers for HIV-associated dementia and sensory neuropathy, in12th World AIDS Conference. Geneva, Switzerland.

  • McArthur JC, N Haughey, S Gartner, K Conant, C Pardo, A Nath and N Sacktor (2003) Human immunodeficiency virus-associated dementia: an evolving disease.J. Neurovirol. 9,205–221.

    Article  PubMed  CAS  Google Scholar 

  • McCoig C, MM Castrejon, E Castano, O De Suman, C Baez, W Redondo, D McClernon, S Danehower, ER Lanier, C Richardson, A Keller, S Hetherington, X Saez-Llorens and O Ramilo (2002) Effect of combination antiretroviral therapy on cerebrospinal fluid HIV RNA, HIV resistance, and clinical manifestations of encephalopathy.J. Pediatr. 141, 36–44.

    Article  PubMed  CAS  Google Scholar 

  • Merrill JE, Y Koyanagi, J Zack, L Thomas, FA Martin and ISY Chen (1992) Induction of interleukin-1 and tumor necrosis factor alpha in brain cultures by human deficiency virus type 1.J. Virol. 66, 2217–2225.

    PubMed  CAS  Google Scholar 

  • Meucci O, A Fatatis, AA Simen, TJ Bushell, PW Gray and RJ Miller (1998) Chemokines regulate hippocampal neuronal signaling and gp120 neurotoxicity.Proc. Natl. Acad. Sci. USA 95, 14500–14505.

    Article  PubMed  CAS  Google Scholar 

  • Meyerhoff DJ, S MacKay, L Bachman, N Poole, WP Dillon, MW Weiner and G Fein (1993) Reduced brain N-acetylaspartate suggests neuronal loss in cognitively impaired human immunodeficiency virus-seropositive individuals:in vivo 1H magnetic resonance spectroscopic imaging.Neurology 43, 509–515.

    PubMed  CAS  Google Scholar 

  • Meyerhoff DJ, S MacKay, N Poole, WP Dillon, MW Weiner and G Fein (1994)N-acetylaspartate reductions measured by 1H MRSI in cognitively impaired HIV-seropositive individuals.Magn. Reson. Imaging 12, 653–659.

    Article  PubMed  CAS  Google Scholar 

  • Meyerhoff DJ, C Bloomer, V Cardenas, D Norman, MW Weiner and G Fein (1999) Elevated subcortical choline metabolites in cognitively and clinically asymptomatic HIV+ patients.Neurology 52 (5), 995–1003.

    PubMed  CAS  Google Scholar 

  • Miller EN, OA Selnes, JC McArthur, P Satz, JT Becker, BA Cohen, K Sheridan, AM Machado, WG Van Gorp and B Visscher (1990) Neuropsychological performance in HIV-1-infected homosexual men: The Multicenter AIDS Cohort Study (MACS).Neurology 40 (2), 197–203.

    PubMed  CAS  Google Scholar 

  • Miller EN, P Satz and B Visscher (1991) Computerized and conventional neuropsychological assessment of HIV-1-infected homosexual men.Neurology 41, 1608–1616.

    PubMed  CAS  Google Scholar 

  • Mizuno T, J Kawanokuchi, K Numata and A Suzumura (2003) Production and neuroprotective functions of fractalkine in the central nervous system.Brain Res. 979 (1–2), 65–70.

    Article  PubMed  CAS  Google Scholar 

  • Nath A, NJ Haughey, J Melina, C Anderson, JE Bell and JD Geiger (2000) Synergistic neurotoxicity human immunodeficiency virus proteins tat and gp120: protection by memantine.Ann. Neurol. 47, 186–194.

    Article  PubMed  CAS  Google Scholar 

  • Navia BA and RG Gonzalez (1997) Functional imaging of the AIDS dementia complex and the metabolic pathology of the HIV- 1-infected brain, In:Neuroimaging of AIDS II (Post J, Ed.), pp 431–445.

  • Navia BA and RW Price (1987) The acquired immunodeficiency syndrome dementia complex as the presenting sole manifestation of human immunodeficiency virus infection.Arch. Neurol. 44, 65–69.

    PubMed  CAS  Google Scholar 

  • Navia BA, BD Jordan and RW Price (1986a) The AIDS dementia complex: I. Clinical features.Ann. Neurol. 19, 517–524.

    Article  PubMed  CAS  Google Scholar 

  • Navia BA, ES Cho, CK Petito and RW Price (1986b) The AIDS dementia complex: II. Neuropathology.Ann. Neurol. 19, 525–535.

    Article  PubMed  CAS  Google Scholar 

  • Navia BA, U Dafni, D Simpson, T Tucker, E Singer, JC McArthur, C Yiannoutsos, L Zaborski and SA Lipton (1998) A phase I/II trial of nimodipine for HIV-related neurologic complications.Neurology 51, 221–228.

    PubMed  CAS  Google Scholar 

  • Navia BA, C Yiannoutsos, R Ellis, G Schifitto, A Nath, S Shriver, L Millar and SA Lipton (2005) Memantine may prevent further cognitive decline in subjects with the AIDS dementia complex with detectable CSF HIV RNA.Neurology (in Press).

  • New DR, SB Maggirwar, LG Epstein, S Dewhurst and HA Gelbard (1998) HIV-1 Tat induces neuronal death via tumor necrosis factor-α and activation of non-N-methyl-D-aspartate receptors by a NFΚB-independent mechanism.J. Biol. Chem. 273, 17852–17858.

    Article  PubMed  CAS  Google Scholar 

  • Nockher WA, L Bergmann and JE Scherberich (1994) Increased soluble CD 14 serum levels and altered CD 14 expression of peripheral blood monocytes in HIV-infected patients.Clin. Exp. Immunol. 98, 369–374.

    PubMed  CAS  Google Scholar 

  • Ohagen A, S Ghosh, J He, K Huang, Y Chen, M Yuan, R Osathanondh, S Gartner, B Shi, G Shaw and D Gabuzda (1999) Apoptosis induced by infection of primary brain cultures with diverse human immunodeficiency virus type 1 isolates: evidence for a role of the envelope.J. Virol. 73, 897–906.

    PubMed  CAS  Google Scholar 

  • Osowiecki D, R Cohen, KM Morrow, R Paul, C Carpenter, T Flanigan and RR Boland (2000) Neuropsychological and psychological contributions to quality of life in HIV-infected women.AIDS 14, 1327–1332.

    Article  PubMed  CAS  Google Scholar 

  • Palella FJ Jr, KM Delaney, AC Moorman, MO Loveless, J Fuhrer, GA Satten, DJ Aschman and SD Holmberg (1998) Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators.N. Engl. J. Med. 338 (13), 853–860.

    Article  PubMed  Google Scholar 

  • Paul R, R Cohen and B Navia (2002) Neuroimaging relationships to cognition in patients with HIV.Neurosci. Biobehav. Rev. 26 (3), 353–359.

    Article  PubMed  Google Scholar 

  • Paul R, T Flanigan, B Navia, N Makris, C Hinkin, J Gunstad, A Jefferson, R Cohen, D Tate and A Brickman (2005) Cognition is associated with caudate volume in patients infected with HIV (submitted).

  • Petito CK and KS Cash (1992) Blood brain barrier abnormalities in the acquired immune deficiency syndrome: immunohistochemical localization of serum proteins to postmortem brains.Ann. Neurol. 32, 658–666.

    Article  PubMed  CAS  Google Scholar 

  • Petito CK and B Roberts (1995) Evidence of apoptotic cell death in HIV encephalitis.Am. J. Pathol. 146, 1121–1130.

    PubMed  CAS  Google Scholar 

  • Petito CK, BA Navia, E-S Cho, BD Jordan, DC George and RW Price (1985) Vacuolar myleopathy pathologically resembling subacute combination degeneration in patients with acquired immunodeficiency syndrome.N. Engl. J. Med. 312, 874–879

    Article  PubMed  CAS  Google Scholar 

  • Petito CK, B Roberts, JD Cantando, A Rabinstein and R Duncan (2001) Hippocampal injury and alterations in neuronal chemokine co-receptor expression in patients with AIDS.J. Neuropathol. Exp. Neurol. 60, 377–385.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Power C, PA Kong, TO Crawford, S Wesselingh, JD Glass, JC McArthur and BD Trapp (1993) Cerebral white matter changes in acquired human immunodeficiency syndrome dementia: alterations of the blood-brain barrier.Ann. Neurol. 34, 339–350.

    Article  PubMed  CAS  Google Scholar 

  • Power C, JC McArthur, RT Johnson, DE Griffin, JD Glass, S Perryman and B Chesebro (1994) Demented and nondemented patients with AIDS differ in brain-derived human immunodeficiency virus type 1 envelope sequences.J. Virol. 68, 4643–4649.

    PubMed  CAS  Google Scholar 

  • Power C, JC McArthur, A Nath, K Wehrly, M Mayne, J Nishio, T Langelier, RT Johnson and B Chesebro (1998) Neuronal death induced by brain-derived human immunodeficiency virus type 1 envelope genes differs between demented and nondemented AIDS patients.J. Virol. 72, 9045–9053.

    PubMed  CAS  Google Scholar 

  • Price RW and B Brew (1988) Management of the neurologic complications of HIV infection and AIDS.Infect. Dis. 2, 359–372.

    CAS  Google Scholar 

  • Price RW and JJ Sidtis (1990) Evaluation of the AIDS dementia complex in clinical trials.J. Acquir. Immune. Defic. Syndr. 3 (Suppl. 2), S51-S60.

    PubMed  Google Scholar 

  • Pulliam L, R Gascon, M Stubblebine, D McGuire and MS McGrath (1997) Unique monocyte subset in patients with AIDS dementia.Lancet 349, 692–695.

    Article  PubMed  CAS  Google Scholar 

  • Pumarola-Sune T, BA Navia and C Cordon-Cardi (1987) HIV antigen in the brains of patients with the AIDS dementia complex.Ann. Neurol. 21, 490–496.

    Article  PubMed  CAS  Google Scholar 

  • Quasney MW, Q Zhang, S Sargent, M Mynatt, J Glass and J McArthur (2001) Increased frequency of the tumor necrosis factor-alpha-308 A allele in adults with human immunodeficiency virus dementia.Ann. Neurol. 50, 157–162.

    Article  PubMed  CAS  Google Scholar 

  • Ragin AB, P Storey, BA Cohen, LG Epstein and RR Edelman (2004) Whole brain diffusion tensor imaging in HIV-associated cognitive impairment.Am. J. Neuroradiol. 25, 195–200.

    PubMed  Google Scholar 

  • Reddy RT, CL Achim, DA Sirko, S Tehranchi, FG Kraus, F Wong-Staal and CA Wiley (1996) Sequence analysis of the V3 loop in brain and spleen of patients with HIV encephalitis.AIDS Res. Hum. Retrovir. 12, 477–482.

    PubMed  CAS  Google Scholar 

  • Reisberg B, R Doody, A Stoffler, F Schmitt, S Ferris and HJ Mobius (2003) Memantine in moderate-to-severe Alzheimer’s disease.N. Engl. J. Med. 348 (14), 1333–1341.

    Article  PubMed  CAS  Google Scholar 

  • Rippeth JD, RK Heaton, CL Carey, TD Marcotte, DJ Moore, R Gonzalez, T Wolfson, I Grant and the HNRC Group (2004) Methamphetamine dependence increases risk of neuropsychological impairment in HIV infected persons.J. Int. Neuropsychol. Soc. 10 (1), 1–14.

    Article  PubMed  CAS  Google Scholar 

  • Robertson K, S Fiscus, C Kapoor, W Robertson, G Schneider, R Shepard, L Howe, S Silva and C Hall (1998) CSF, plasma viral load and HIV associated dementia.J. Neurovirol. 4, 90–94.

    PubMed  CAS  Google Scholar 

  • Robertson KR, WT Robertson, S Ford, D Watson, S Fiscus, AG Harp and CD Hall (2004) Highly active antiretroviral therapy improves neurocognitive functioning.J. Acquir. Immune Defic. Syndr. 36 (1), 562–566.

    Article  PubMed  Google Scholar 

  • Rostasy K, L Monti, C Yiannoutsos, M Kneissl, J Bell, TL Kemper, JC Hedreen and BA Navia (1999) Human immunodeficiency virus infection, inducible nitric oxide synthase expression, and microglial activation: pathogenetic relationship to the acquired immunodeficiency syndrome dementia complex.Ann. Neurol. 46 (2), 207–216.

    Article  PubMed  CAS  Google Scholar 

  • Rostasy K, L Monti, C Yiannoutsos, J Wu, J Bell, J Hedreen and BA Navia (2000) NFΚB activation, TNF-α expression and apoptosis in the AIDS dementia Complex.J. Neurovirol. 6, 537–543.

    Article  PubMed  CAS  Google Scholar 

  • Rostasy K, C Egles, A Chauhan, M Kneissl, P Bahrani, C Yiannoutsos, DD Hunter, A Nath, JC Hedreen and BA Navia (2003) SDF-1 alpha is expressed in astrocytes and neurons in the AIDS dementia complex: anin vivo andin vitro study.J. Neuropathol. Exp. Neurol. 62 (6), 617–626.

    PubMed  CAS  Google Scholar 

  • Rostasy K, G Gorgun, Y Kleyner, A Garcia, SM Melanson, JM Mathys, C Yiannoutsos, PR Skolnik and BA Navia (2005a) Tumor necrosis factor-α leads to increased cell surface expression of the chemokine receptor CXCR4 in SK-N-MC cells.J. Neurovirol. 11 (3) 247–255.

    Article  PubMed  CAS  Google Scholar 

  • Rostasy K, L Monti, M Kneissl, SA Lipton, J Hedreen, RG Gonzalez and BA Navia (2005b) HIV Leukoencephalopathy and TNF-α expression in neurons.J. Neurol. Neurosurg. Psychiatr. 76(7) 960–964.

    Article  PubMed  CAS  Google Scholar 

  • Rottenberg DA, JR Moeller, SC Strother, JJ Sidtis, BA Navia, V Dhawan, JZ Ginos and RW Price (1987) The metabolic pathology of the AIDS dementia complex.Ann. Neurol. 22, 700–706.

    Article  PubMed  CAS  Google Scholar 

  • Ryan LA, J Zheng, M Brester, D Bohac, F Hahn, J Anderson, W Ratanasuwan, GE Gendelman and S Swindells (2001) Plasma levels of soluble CD14 and tumor necrosis factor-alpha type II receptor correlate with cognitive dysfunction during human immunodeficiency virus type 1 infection.J. Infect. Dis. 184 (6), 699–706.

    Article  PubMed  CAS  Google Scholar 

  • Sacktor N (2002) The epidemiology of human immunodeficiency virus-associated neurological disease in the era of highly active antiretroviral therapy.J. Neurovirol. 8 (Suppl. 2), 115–121.

    Article  PubMed  CAS  Google Scholar 

  • Sacktor NC, H Bacellar, DR Hoover, TE Nance-Sproson, OA Selnes, EN Miller, GJ Dal Pan, C Kleeberger, A Brown, A Saah and JC McArthur (1996) Psychomotor slowing in HIV infection: a predictor of dementia, AIDS and death.J. Neurovirol. 2, 404–410.

    Article  PubMed  CAS  Google Scholar 

  • Sacktor N, G Schifitto, MP McDermott, K Marder, JC McArthur and K Kieburtz (2000) Transdermal selegiline in HIV-associated cognitive impairment: pilot placebo-controlled study.Neurology 54, 233–235.

    PubMed  CAS  Google Scholar 

  • Sacktor N, MP McDermott, K Marder, G Schifitto, OA Selnes, JC McArthur, Y Stern, S Albert, D Palumbo, K Kieburtz, JA De Marcaida, B Cohen and L Epstein (2002) HIV-associated cognitive impairment before and after the advent of combination therapy.J. Neurovirol. 8 (2), 136–142.

    Article  PubMed  CAS  Google Scholar 

  • Salvan AM, J Vion-Dury, S Confort-Gouny, F Nicoli, S Lamoureux and PJ Cozzone (1997) Brain proton magnetic resonance spectroscopy in HIV-related encephalopathy: identification of evolving metabolic patterns in relation to dementia and therapy.AIDS Res. Hum. Retroviruses 13, 1055–1066.

    Article  PubMed  CAS  Google Scholar 

  • Sasseville VG, MM Smith, CR Mackay, DR Pauley, KG Mansfield, DJ Ringler and AA Lackner (1996) Chemokine expression in simian immunodeficiency virus-induced AIDS encephalitis.Am. J. Pathol. 149, 459–467.

    Google Scholar 

  • Schifitto G, N Sacktor, K Marder, MP McDermott, JC McArthur, K Kieburtz, S Small and LG Epstein (1999) Randomized trial of the platelet activating factor antagonist lexipafant in HIV-associated cognitive impairment.Neurology 53, 391–396.

    PubMed  CAS  Google Scholar 

  • Schmidtmayerova H, HS Nottet, G Nuovo, T Raabe, CR Flanagan, L Dubrovsky, HE Gendelman, A Cerami, M Bukrinsky and B Sherry (1996) Human immunodeficiency virus type 1 infection alters chemokine beta peptide expression in human monocytes: implications for recruitment of leukocytes into brain and lymph nodes.Proc. Natl. Acad. Sci. USA 93 (2), 700–704.

    Article  PubMed  CAS  Google Scholar 

  • Shi B, U De Girolami, J He, S Wang, A Lorenzo, J Busciglio and D Gabuzda (1996) Apoptosis induced by HIV-1 infection of the central nervous system.J. Clin. Invest. 98, 1979–1990.

    Article  PubMed  CAS  Google Scholar 

  • Sidtis JJ, C Gatsonis, RW Price, EJ Singer, AC Collier, DD Richman, MS Hirsch, FW Schaerf, MA Fischl, K Kieburtz, D Simpson, M Koch, J Feinberg, U Dafni and the AIDS Clinical Trials Group (1993) Zidovudine treatment of the AIDS dementia complex: results of a placebo-controlled trial. AIDS Clinical Trials Group.Ann. Neurol. 33, 343–349.

    Article  PubMed  CAS  Google Scholar 

  • Soriano SG, LS Amaravadi, YF Wang, H Zhou, GX Yu, JR Tonra, V Fairchild-Huntress, Q Fang, JH Dunmore, D Huszar and Y Pan (2002) Mice deficient in fractalkine are less susceptible to cerebral ischemia-reperfusion injury.J. Neuroimmunol. 125, 59–65.

    Article  PubMed  CAS  Google Scholar 

  • Talley AK, S Dewhurst, SW Perry, SC Dollard, S Gummuluru, SM Fine, D New, LG Epstein, HE Gendelman and HA Gelbard (1995) Tumor necrosis factor alpha induced apoptosis in human neuronal cells: protection by the antioxidant N-acetylcysteine and the genes bcl-2 and crm-A.Mol. Cell. Biol. 15, 2359–2366.

    PubMed  CAS  Google Scholar 

  • Tariot PN, MR Farlow, GT Grossberg, SM Graham, S McDonald and I Gergel (2004) Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial.JAMA 291 (3), 317–324.

    Article  PubMed  CAS  Google Scholar 

  • Tate DF, RH Paul, A Brickman, RA Cohen, T Flanigan, BA Navia for the ACTG 700 team and the HIV MRS Consortium (2005) Differential relationships between corpus callosal area and cognition in HIV-infected patients.Int. Neuropsychol. Soc. in press.

  • Taylor MJ, SL Letendre, BC Schweinsburg, OM Alhassoon, GG Brown, A Gongvatana, I Grant and HNRC (2004) Hepatitis C virus infection is associated with reduced white matter N-acetylaspartate in abstinent methamphetamine users.J. Int. Neuropsychol. Soc. 10 (1), 110–113.

    Article  PubMed  CAS  Google Scholar 

  • The Dana Consortium on Therapy for HIV Dementia and Related Cognitive Disorders (1997) Safety and tolerability of the antioxidant OPC-14117 in HIV-associated cognitive impairment.Neurology 49, 142–146.

    Google Scholar 

  • The Dana Consortium on Therapy for HIV Dementia and Related Cognitive Disorders (1998) A randomized, double-blind, placebo-controlled trial of deprenyl and thioctic acid in human immunodeficiency virus-associated cognitive impairment.Neurology 50, 645–651.

    Google Scholar 

  • Toggas S, E Masliah, E Rockenstein, G Rall, C Abraham and L Mucke (1994) Central nervous system damage produced by expression of the HIV-1 coat protein gp120 in transgenic mice.Nature 367, 188–191.

    Article  PubMed  CAS  Google Scholar 

  • Toggas SM, E Masliah and L Mucke (1996) Prevention of HIV-1 gp120 induced neuronal damage in the central nervous system of transgenic mice by the NMDA receptor antagonist memantine.Brain Res. 706, 303–307.

    Article  PubMed  CAS  Google Scholar 

  • Tong N, SW Perry, Q Zhang, HJ James, H Guo, A Brooks, H Bal, SA Kinnear, S Fine, LG Epstein, D Dairaghi, TJ Schall, HE Gendelman, S Dewhurst, LR Sharer and HA Gelbard (2000) Neuronal fractalkine expression in HIV-1 encephalitis: roles for macrophage recruitment and neuroprotection in the central nervous system.J. Immunol. 164, 1333–1339.

    PubMed  CAS  Google Scholar 

  • Torres-Munoz J, P Stockton, N Tacoronte, B Roberts, RR Maronpot and CK Petito (2001) Detection of HIV-1 gene sequences in hippocampal neurons isolated from postmortem AIDS brains by laser capture microdissection.J. Neuropathol. Exp. Neurol. 60, 885–892.

    PubMed  CAS  Google Scholar 

  • Tracey I, CA Carr, AR Guimaraes, JL Worth, BA Navia and RG Gonzalez (1996) Brain choline-containing compounds are elevated in HIV-positive patients before the onset of AIDS dementia complex: a proton magnetic resonance spectroscopic study.Neurology 46, 783–788.

    PubMed  CAS  Google Scholar 

  • Tracey I, LM Hamberg, AR Guimaraes, G Hunter, I Chang, BA Navia and RG Gonzalez (1998) Increased cerebral blood volume in HIV-positive patients detected by functional MRI.Neurology 50, 1821–1826.

    PubMed  CAS  Google Scholar 

  • Tross S, RW Price, B Navia, HT Thaler, J Gold, DA Hirsch and JJ Sidtis (1988) Neuropsychological characterization of the AIDS dementia complex: a preliminary report.AIDS 2, 81–88.

    Article  PubMed  CAS  Google Scholar 

  • van Gorp WG, P Satz, C Hinkin, G Evans and EN Miller (1989) The neuropsychological aspects of HIV-1 spectrum disease.Psychiatr. Med. 7, 59–78.

    PubMed  Google Scholar 

  • van Gorp WG, MA Mandelkern, M Gee, CH Hinkin, CE Stern, DK Paz, W Dixon, G Evans, F Flynn and CJ Frederick (1992) Cerebral metabolic dysfunction in AIDS: findings in a sample with and without dementia.J. Neuropsychiatr. Clin. Neurosci. 4, 280–287.

    Google Scholar 

  • Von Giesen HJ and G Arendt (2002) Drug treatment for HIV-1-associated dementia.Curr. Opin. Investig. Drugs 3, 1643–1646.

    Google Scholar 

  • Wesselingh SL, C Power, JD Glass, WR Tyor, JC McArthur, JM Farber, JW Griffin and DE Griffin (1993) Intracerebral cytokine messenger RNA expression in acquired immunodeficiency syndrome dementia.Ann. Neurol. 33, 576–582.

    Article  PubMed  CAS  Google Scholar 

  • Westmoreland SV, JB Rottman, KC Williams, AA Lackner and VG Sasseville (1998) Chemokine receptor expression on resident and inflammatory cells in the brain of macaques with simian immunodeficiency virus encephalitis.Am. J. Pathol. 152, 659–665.

    PubMed  CAS  Google Scholar 

  • Wiley C and C Achim (1994) Human immunodeficiency virus encephalitis is the pathological correlate of dementia in acquired immunodeficiency syndrome.Ann. Neurol. 36, 673–676.

    Article  PubMed  CAS  Google Scholar 

  • Wiley C, E Masliah and M Morey (1991) Neocortical damage during HIV infection.Ann. Neurol. 29, 651–657.

    Article  PubMed  CAS  Google Scholar 

  • Wilkie FL, K Goodkin, C Eisdorfer, D Feaster, R Morgan, MA Fletcher, N Blaney, M Baum and J Szapocznik (1998) Mild cognitive impairment and risk of mortality in HIV-1 infection.J. Neuropsychiatr. Clin. Neurosci. 10, 125–132.

    CAS  Google Scholar 

  • Yeung MC, L Pulliam and AS Lau (1995) The HIV envelope protein gp 120 is toxic to human brain-cell cultures through the induction of interleukin-6 and tumor necrosis factor.AIDS 9, 137–143.

    Article  PubMed  CAS  Google Scholar 

  • Yiannoutsos CT, T Ernst, L Chang, PL Lee, T Richards, CM Marra, DJ Meyerhoff, JG Jarvik, D Kolson, G Schifitto, RJ Ellis, S Swindells, DM Simpson, EN Miller, RG Gonzalez, BA Navia for the HIV MRS consortium (2004) Patterns of regional brain metabolites in the AIDS Dementia Complex.NeuroImage 23, 928–935.

    Article  PubMed  Google Scholar 

  • Zheng J, A Ghorpade, D Niemann, RL Cotter, MR Thylin, L Epstein, JM Swartz, RB Shepard, X Liu, A Nukuna and HE Gendelman (1999a) Lymphotropic virions affect chemokine receptor-mediated neural signaling and apoptosis: implications for human immunodeficiency virus type 1-associated dementia.J. Virol. 73, 8256–8267.

    PubMed  CAS  Google Scholar 

  • Zheng J, MR Thylin, A Ghorpade, H Xiong, Y Persidsky, R Cotter, D Niemann, M Che, YC Zeng, HA Gelbard, RB Shepard, JM Swartz and HE Gendelman (1999b) Intracellular CXCR4 signaling, neuronal apoptosis and neuropathogenic mechanisms of HIV-1 -associated dementia.J. Neuroimmunol. 98, 185–200.

    Article  PubMed  CAS  Google Scholar 

  • Zink WE, E Anderson, J Boyle, L Hock, J Rodriguez-Sierra, H Xiong, HE Gendelman and Y Persidsky (2002) Impaired spatial cognition and synaptic potentiation in a murine model of human immunodeficiency virus type 1.J. Neurosci. 22, 2096–2105.

    PubMed  CAS  Google Scholar 

  • Zujovic V, N Schussler, D Jourdain, D Duverger and V Taupin (2001)In vivo neutralization of endogenous brain fractalkine increases hippocampal TNFalpha and 8-isoprostane production induced by intracerebroventricular injection of LPS.J. Neuroimmunol. 115, 135–143.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Community Medicine and Infectious Disease, Neurology and Psychiatry, Tufts University School of Medicine, Boston, MA

    Bradford A. Navia

  2. Department of Pediatrics and Pediatric Neurology, Georg- August- University Goettingen, Goettingen, Germany

    Kevin Rostasy

Authors
  1. Bradford A. Navia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kevin Rostasy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bradford A. Navia.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Navia, B.A., Rostasy, K. The AIDS dementia complex: Clinical and basic Neuroscience with implications for novel molecular therapies. neurotox res 8, 3–24 (2005). https://doi.org/10.1007/BF03033817

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03033817

Keywords

Search

Navigation