aids dementia complex

Summary

Summary: A neurologic condition associated with the ACQUIRED IMMUNODEFICIENCY SYNDROME and characterized by impaired concentration and memory, slowness of hand movements, ATAXIA, incontinence, apathy, and gait difficulties associated with HIV-1 viral infection of the central nervous system. Pathologic examination of the brain reveals white matter rarefaction, perivascular infiltrates of lymphocytes, foamy macrophages, and multinucleated giant cells. (From Adams et al., Principles of Neurology, 6th ed, pp760-1; N Engl J Med, 1995 Apr 6;332(14):934-40)

Top Publications

  1. SAS A, Bimonte Nelson H, Smothers C, Woodward J, Tyor W. Interferon-alpha causes neuronal dysfunction in encephalitis. J Neurosci. 2009;29:3948-55 pubmed publisher
    ..Blocking IFNalpha could be important in improving cognitive and pathological developments in HAD patients and may be clinically important in other neuroinflammatory diseases as well...
  2. Valcour V, Shiramizu B, Shikuma C. HIV DNA in circulating monocytes as a mechanism to dementia and other HIV complications. J Leukoc Biol. 2010;87:621-6 pubmed publisher
    ..Herein, we summarize our current understanding of monocyte HIV DNA and central nervous system dysfunction in humans. We present a model to understand these relationships and suggest possible treatment approaches to be tested...
  3. Lanoy E, Guiguet M, Bentata M, Rouveix E, Dhiver C, Poizot Martin I, et al. Survival after neuroAIDS: association with antiretroviral CNS Penetration-Effectiveness score. Neurology. 2011;76:644-51 pubmed publisher
  4. Lyon M, McCarter R, D Angelo L. Detecting HIV associated neurocognitive disorders in adolescents: what is the best screening tool?. J Adolesc Health. 2009;44:133-135 pubmed publisher
    ..The HDS identified five of these cases (83% sensitivity, 76% specificity). The MMSE identified three cases (50% sensitivity, 92% specificity). Based on the study results, the HDS appears to be clinically useful. ..
  5. Yang B, Singh S, Bressani R, Kanmogne G. Cross-talk between STAT1 and PI3K/AKT signaling in HIV-1-induced blood-brain barrier dysfunction: role of CCR5 and implications for viral neuropathogenesis. J Neurosci Res. 2010;88:3090-101 pubmed publisher
    ..These results suggest that the chemokine receptor CCR5 is partially involved in HIV-1 binding to HBMEC and show cross-talk between STAT1 and PI3K pathways in HIV-1-induced BBB dysfunction...
  6. Boivin M, Ruel T, Boal H, Bangirana P, Cao H, Eller L, et al. HIV-subtype A is associated with poorer neuropsychological performance compared with subtype D in antiretroviral therapy-naive Ugandan children. AIDS. 2010;24:1163-70 pubmed
    ..HIV-subtype D is associated with more rapid disease progression and higher rates of dementia in Ugandan adults compared with HIV-subtype A. There are no data comparing neuropsychological function by HIV subtype in Ugandan children...
  7. Fritz French C, Tyor W. Interferon-? (IFN?) neurotoxicity. Cytokine Growth Factor Rev. 2012;23:7-14 pubmed publisher
    ..Development of therapeutics that block IFN? may prove to be an effective treatment of HAND and other inflammatory conditions where there is increased CNS IFN?...
  8. Cysique L, Waters E, Brew B. Central nervous system antiretroviral efficacy in HIV infection: a qualitative and quantitative review and implications for future research. BMC Neurol. 2011;11:148 pubmed publisher
    ..The current review aims to better synthesise existing literature by using an innovative two-phase review approach (qualitative and quantitative) to overcome methodological differences between studies...
  9. Joska J, Gouse H, Paul R, Stein D, Flisher A. Does highly active antiretroviral therapy improve neurocognitive function? A systematic review. J Neurovirol. 2010;16:101-14 pubmed publisher
    ..Studies examining the long-term effects of HAART on HIV-associated neurocognitive disorders (HANDs) using uniform methods of data collection are needed, together with clear reporting of HAART regimens...

More Information

Publications62

  1. Newsome S, Johnson E, Pardo C, McArthur J, Nath A. Fulminant encephalopathy with basal ganglia hyperintensities in HIV-infected drug users. Neurology. 2011;76:787-94 pubmed publisher
    ..To define a clinical syndrome associated with active drug abuse in HIV-infected individuals...
  2. Churchill M, Wesselingh S, Cowley D, Pardo C, McArthur J, Brew B, et al. Extensive astrocyte infection is prominent in human immunodeficiency virus-associated dementia. Ann Neurol. 2009;66:253-8 pubmed publisher
    ..Our data indicate that astrocytes can be extensively infected with HIV, and suggest an important role for HIV-infected astrocytes in HIV neuropathogenesis...
  3. Pitcher J, Shimizu S, Burbassi S, Meucci O. Disruption of neuronal CXCR4 function by opioids: preliminary evidence of ferritin heavy chain as a potential etiological agent in neuroAIDS. J Neuroimmunol. 2010;224:66-71 pubmed publisher
  4. Ju S, Song H, Lee J, Lee S, Choi S, Park J. Extracellular HIV-1 Tat up-regulates expression of matrix metalloproteinase-9 via a MAPK-NF-kappaB dependent pathway in human astrocytes. Exp Mol Med. 2009;41:86-93 pubmed
    ..Taken together, our results indicate that HIV-1 Tat can up-regulate expression of MMP-9 via MAPK-NF-kappaB-dependent mechanisms as well as Tat-induced TNF-alpha production in astrocytes...
  5. Gisslen M, Price R, Nilsson S. The definition of HIV-associated neurocognitive disorders: are we overestimating the real prevalence?. BMC Infect Dis. 2011;11:356 pubmed publisher
    ..This includes a new disorder that has been termed asymptomatic neurocognitive impairment (ANI)...
  6. Joska J, Fincham D, Stein D, Paul R, Seedat S. Clinical correlates of HIV-associated neurocognitive disorders in South Africa. AIDS Behav. 2010;14:371-8 pubmed publisher
    ..This underlines the impact of HIV on the nervous system and the importance of screening for co morbid mental health conditions...
  7. Gongvatana A, Schweinsburg B, Taylor M, Theilmann R, Letendre S, Alhassoon O, et al. White matter tract injury and cognitive impairment in human immunodeficiency virus-infected individuals. J Neurovirol. 2009;15:187-95 pubmed publisher
    ..The study also confirms that CNS injury is evident in persons infected with HIV despite effective antiretroviral treatment...
  8. Mothobi N, Brew B. Neurocognitive dysfunction in the highly active antiretroviral therapy era. Curr Opin Infect Dis. 2012;25:4-9 pubmed publisher
  9. Gelman B, Nguyen T. Synaptic proteins linked to HIV-1 infection and immunoproteasome induction: proteomic analysis of human synaptosomes. J Neuroimmune Pharmacol. 2010;5:92-102 pubmed publisher
    ..Proteomics illustrates that certain human proteins within the synaptic compartment are involved with changes in the synaptodendritic arbor and neurocognitive impairment in HIV-1-infected people...
  10. Garvey L, Winston A, Walsh J, Post F, Porter K, Gazzard B, et al. HIV-associated central nervous system diseases in the recent combination antiretroviral therapy era. Eur J Neurol. 2011;18:527-34 pubmed publisher
    ..Data describing the incidence and survival of HIV-related central nervous system diseases (CNS-D) in recent years are sparse...
  11. Choi Y, Townend J, Vincent T, Zaidi I, Sarge Njie R, Jaye A, et al. Neurologic manifestations of human immunodeficiency virus-2: dementia, myelopathy, and neuropathy in West Africa. J Neurovirol. 2011;17:166-75 pubmed publisher
    ..Similar to HIV-1, DSPN seems to occur with lower CD4 counts in HIV-2. Further study of the viral-host interactions in HIV-2 and its consequent neurological diseases may provide an avenue for understanding the epidemic problems of HIV-1...
  12. Xu J, Ikezu T. The comorbidity of HIV-associated neurocognitive disorders and Alzheimer's disease: a foreseeable medical challenge in post-HAART era. J Neuroimmune Pharmacol. 2009;4:200-12 pubmed publisher
    ..A growing awareness of potential convergent mechanisms leading to neurodegeneration shared by HIV and Abeta points to a significant chance of comorbidity of AD and HAND in senile HIV patients, which calls for a need of basic studies...
  13. Bonnet F, Amieva H, Marquant F, Bernard C, Bruyand M, Dauchy F, et al. Cognitive disorders in HIV-infected patients: are they HIV-related?. AIDS. 2013;27:391-400 pubmed publisher
  14. McArthur J, Brew B. HIV-associated neurocognitive disorders: is there a hidden epidemic?. AIDS. 2010;24:1367-70 pubmed publisher
  15. Nakasujja N, Miyahara S, Evans S, Lee A, Musisi S, Katabira E, et al. Randomized trial of minocycline in the treatment of HIV-associated cognitive impairment. Neurology. 2013;80:196-202 pubmed publisher
    ..To evaluate the efficacy and safety of minocycline in the management of HIV-associated cognitive impairment...
  16. 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 pubmed publisher
    ..To determine whether cognitive impairment and brain injury as measured by proton magnetic resonance spectroscopy (MRS) persist in the setting of HAART...
  17. Perez Valero I, Bayón C, Cambron I, Gonzalez A, Arribas J. Protease inhibitor monotherapy and the CNS: peace of mind?. J Antimicrob Chemother. 2011;66:1954-62 pubmed publisher
    ..It is clear that more studies including detailed neurocognitive testing are needed to completely establish the risk/benefit ratio of bPI monotherapy or triple-drug HAART for preserving neurocognitive function in HIV-infected patients...
  18. Borjabad A, Morgello S, Chao W, Kim S, Brooks A, Murray J, et al. Significant effects of antiretroviral therapy on global gene expression in brain tissues of patients with HIV-1-associated neurocognitive disorders. PLoS Pathog. 2011;7:e1002213 pubmed publisher
    ..Aberrantly expressed transcripts common to untreated and treated HAND may contribute to neurocognitive changes defying ART...
  19. Gorantla S, Poluektova L, Gendelman H. Rodent models for HIV-associated neurocognitive disorders. Trends Neurosci. 2012;35:197-208 pubmed publisher
    ..We review these and other rodent models of HAND and discuss their unmet potential in reflecting human pathobiology and in facilitating disease monitoring and therapeutic discoveries...
  20. Wendelken L, Valcour V. Impact of HIV and aging on neuropsychological function. J Neurovirol. 2012;18:256-63 pubmed publisher
    ..This review summarizes knowledge of cognition in HIV as it relates to age and presents some emerging controversies...
  21. Kamat A, Lyons J, Misra V, Uno H, Morgello S, Singer E, et al. Monocyte activation markers in cerebrospinal fluid associated with impaired neurocognitive testing in advanced HIV infection. J Acquir Immune Defic Syndr. 2012;60:234-43 pubmed publisher
    ..To examine relationships of monocyte activation markers to HAND of varying severity, we compared plasma and cerebrospinal fluid (CSF) biomarker levels with neurocognitive test scores in HIV+ subjects...
  22. Schnell G, Spudich S, Harrington P, Price R, Swanstrom R. Compartmentalized human immunodeficiency virus type 1 originates from long-lived cells in some subjects with HIV-1-associated dementia. PLoS Pathog. 2009;5:e1000395 pubmed publisher
    ..We propose a model in which infiltrating macrophages replace CD4(+) T cells as the primary source of productive viral replication in the CNS to maintain high viral loads in the CSF in a substantial subset of subjects with HAD...
  23. Zhou L, Rua R, Ng T, Vongrad V, Ho Y, Geczy C, et al. Evidence for predilection of macrophage infiltration patterns in the deeper midline and mesial temporal structures of the brain uniquely in patients with HIV-associated dementia. BMC Infect Dis. 2009;9:192 pubmed publisher
    ..HIV-1 penetrates the central nervous system, which is vital for HIV-associated dementia (HAD). But the role of cellular infiltration and activation together with HIV in the development of HAD is poorly understood...
  24. Valcour V, Shiramizu B, Sithinamsuwan P, Nidhinandana S, Ratto Kim S, Ananworanich J, et al. HIV DNA and cognition in a Thai longitudinal HAART initiation cohort: the SEARCH 001 Cohort Study. Neurology. 2009;72:992-8 pubmed publisher
    ..These findings raise the possibility that short-term incomplete cognitive recovery with HAART may represent an active process related to this peripheral reservoir. ..
  25. Merino J, Montes M, Blanco A, Bustos M, Oreja Guevara C, Bayon C, et al. [HIV-1 neuropathogenesis: therapeutic strategies against neuronal loss induced by gp120/Tat glycoprotein in the central nervous system]. Rev Neurol. 2011;52:101-11 pubmed
    ..These trials have shown that their treatments are beneficial and complementary to treat complications of HIV/AIDS...
  26. Robbins R, Remien R, Mellins C, Joska J, Stein D. Screening for HIV-associated dementia in South Africa: potentials and pitfalls of task-shifting. AIDS Patient Care STDS. 2011;25:587-93 pubmed publisher
  27. Ellis R, Badiee J, Vaida F, Letendre S, Heaton R, Clifford D, et al. CD4 nadir is a predictor of HIV neurocognitive impairment in the era of combination antiretroviral therapy. AIDS. 2011;25:1747-51 pubmed publisher
  28. Kraft Terry S, Buch S, Fox H, Gendelman H. A coat of many colors: neuroimmune crosstalk in human immunodeficiency virus infection. Neuron. 2009;64:133-45 pubmed publisher
    ..Better understanding of the complexities of immune regulation during HAND can improve diagnosis and disease outcomes but is also relevant for the pathogenesis of a broad range of neurodegenerative disorders...
  29. Lyons J, Uno H, Ancuta P, Kamat A, Moore D, Singer E, et al. Plasma sCD14 is a biomarker associated with impaired neurocognitive test performance in attention and learning domains in HIV infection. J Acquir Immune Defic Syndr. 2011;57:371-9 pubmed publisher
    ..To examine these relationships, we compared plasma soluble CD14 (sCD14), CCL2, and LPS levels with neurocognitive test scores in a cART era cohort...
  30. Nguyen T, Soukup V, Gelman B. Persistent hijacking of brain proteasomes in HIV-associated dementia. Am J Pathol. 2010;176:893-902 pubmed publisher
    ..This would disrupt neuronal and synaptic protein dynamics, contributing to HIV-1 neurocognitive disturbances...
  31. Noorbakhsh F, Overall C, Power C. Deciphering complex mechanisms in neurodegenerative diseases: the advent of systems biology. Trends Neurosci. 2009;32:88-100 pubmed publisher
  32. Gelman B, Lisinicchia J, Chen T, Johnson K, Jennings K, Freeman D, et al. Prefrontal dopaminergic and enkephalinergic synaptic accommodation in HIV-associated neurocognitive disorders and encephalitis. J Neuroimmune Pharmacol. 2012;7:686-700 pubmed publisher
    ..Emulating endogenous synaptic plasticity pharmacodynamically could enhance synaptic accommodation and improve neuropsychological and neuropathological outcomes in HIV/AIDS. ..
  33. Zhang Y, Qiao L, Ding W, Wei F, Zhao Q, Wang X, et al. An initial screening for HIV-associated neurocognitive disorders of HIV-1 infected patients in China. J Neurovirol. 2012;18:120-6 pubmed publisher
    ..Cognitive and behavioral disorder is major complaint rather than cognitive and motor impairment. A larger prospective study is needed to obtain better estimates of HAND in China...
  34. Lindl K, Marks D, Kolson D, Jordan Sciutto K. HIV-associated neurocognitive disorder: pathogenesis and therapeutic opportunities. J Neuroimmune Pharmacol. 2010;5:294-309 pubmed publisher
    ..By considering the specific mechanisms and consequences of HIV neuropathogenesis, unified approaches for neuroprotection will likely emerge using a tailored, combined, and non-invasive approach...
  35. Lawler K, Mosepele M, Ratcliffe S, Seloilwe E, Steele K, Nthobatsang R, et al. Neurocognitive impairment among HIV-positive individuals in Botswana: a pilot study. J Int AIDS Soc. 2010;13:15 pubmed publisher
  36. Maruff P, Thomas E, Cysique L, Brew B, Collie A, Snyder P, et al. Validity of the CogState brief battery: relationship to standardized tests and sensitivity to cognitive impairment in mild traumatic brain injury, schizophrenia, and AIDS dementia complex. Arch Clin Neuropsychol. 2009;24:165-78 pubmed publisher
    ..of performance on the CogState tasks in groups of individuals with mild head injury, schizophrenia, and AIDS dementia complex. Each of these groups was impaired on the CogState performance measures (Cohen's d's = -.60 to -1...
  37. Xing H, Hayakawa H, Gelpi E, Kubota R, Budka H, Izumo S. Reduced expression of excitatory amino acid transporter 2 and diffuse microglial activation in the cerebral cortex in AIDS cases with or without HIV encephalitis. J Neuropathol Exp Neurol. 2009;68:199-209 pubmed publisher
    ..The expression of EAAT-2 by activated microglia suggests that they might exert a compensatory effect that protects neurons from glutamate neurotoxicity...
  38. Ruel T, Boivin M, Boal H, Bangirana P, Charlebois E, Havlir D, et al. Neurocognitive and motor deficits in HIV-infected Ugandan children with high CD4 cell counts. Clin Infect Dis. 2012;54:1001-9 pubmed publisher
  39. Ances B, Clifford D. HIV-associated neurocognitive disorders and the impact of combination antiretroviral therapies. Curr Neurol Neurosci Rep. 2008;8:455-61 pubmed
    ..Because viral control generally has been successful without eliminating cognitive dysfunction, further clinical studies that assess adjunctive neuroprotective drugs are likely to be required...
  40. Ragin A, D Souza G, REYNOLDS S, Miller E, Sacktor N, Selnes O, et al. Platelet decline as a predictor of brain injury in HIV infection. J Neurovirol. 2011;17:487-95 pubmed publisher
    ..Findings from a structural brain imaging substudy of older participants, however, support a possible relationship between platelet decline and reduced gray matter...
  41. Gorantla S, Makarov E, Roy D, Finke Dwyer J, Murrin L, Gendelman H, et al. Immunoregulation of a CB2 receptor agonist in a murine model of neuroAIDS. J Neuroimmune Pharmacol. 2010;5:456-68 pubmed publisher
    ..Gp1a down modulated CCR5 expression on human cells in the spleen with an increase in Fas ligand expression. Our results support the notion that CB2 receptor agonists may be a viable therapeutic candidate for HAND...
  42. Kraft Terry S, Stothert A, Buch S, Gendelman H. HIV-1 neuroimmunity in the era of antiretroviral therapy. Neurobiol Dis. 2010;37:542-8 pubmed publisher
    ..Current therapeutic approaches are focused on adjunctive and brain-penetrating antiretroviral therapies. These may attenuate virus-associated neuroinflammatory activities thereby decreasing the severity and frequency of HAND...
  43. Joska J, Westgarth Taylor J, Hoare J, Thomas K, Paul R, Myer L, et al. Validity of the International HIV Dementia Scale in South Africa. AIDS Patient Care STDS. 2011;25:95-101 pubmed publisher
    ..Variable performance in neuropsychological testing may account for false negative screens. The inclusion of brief tests of executive function in a screening battery should be considered...
  44. Valcour V, Sithinamsuwan P, Letendre S, Ances B. Pathogenesis of HIV in the central nervous system. Curr HIV/AIDS Rep. 2011;8:54-61 pubmed publisher
    ..This review highlights recent investigations of HIV-related CNS injury with emphasis on cART-era neuropathological mechanisms in the context of both US and international settings...
  45. Andres M, Feger U, Nath A, Munsaka S, Jiang C, Chang L. APOE ε 4 allele and CSF APOE on cognition in HIV-infected subjects. J Neuroimmune Pharmacol. 2011;6:389-98 pubmed publisher
  46. Schouten J, Cinque P, Gisslen M, Reiss P, Portegies P. HIV-1 infection and cognitive impairment in the cART era: a review. AIDS. 2011;25:561-75 pubmed publisher
    With the introduction of combination antiretroviral therapy AIDS dementia complex or HIV-associated dementia, as it was termed later, largely disappeared in clinical practice...
  47. Agrawal L, Louboutin J, Reyes B, Van Bockstaele E, Strayer D. HIV-1 Tat neurotoxicity: a model of acute and chronic exposure, and neuroprotection by gene delivery of antioxidant enzymes. Neurobiol Dis. 2012;45:657-70 pubmed publisher
  48. Thomas A, Bodner A, Ghadge G, Roos R, Slusher B. GCP II inhibition rescues neurons from gp120IIIB-induced neurotoxicity. J Neurovirol. 2009;15:449-57 pubmed publisher
    ..Taken together, these data suggest that GCP II is involved in mediating gp120-induced apoptosis in hippocampal neurons and GCP II inhibitors may have potential in the treatment of neuronal injury related to AIDS...
  49. Ances B, Roc A, Korczykowski M, Wolf R, Kolson D. Combination antiretroviral therapy modulates the blood oxygen level-dependent amplitude in human immunodeficiency virus-seropositive patients. J Neurovirol. 2008;14:418-24 pubmed publisher
    ..An increase in the BOLD fMRI response in HIV patients on low-CPE cART may reflect continued HIV replication in the CNS leading to increased oxidative stress and associated metabolic demands...
  50. Jevtovic D, Vanovac V, Veselinovic M, Salemovic D, Ranin J, Stefanova E. The incidence of and risk factors for HIV-associated cognitive-motor complex among patients on HAART. Biomed Pharmacother. 2009;63:561-5 pubmed publisher
  51. Valcour V, Watters M, Williams A, Sacktor N, McMurtray A, Shikuma C. Aging exacerbates extrapyramidal motor signs in the era of highly active antiretroviral therapy. J Neurovirol. 2008;14:362-7 pubmed publisher
    ..These results highlight the importance of a careful neurological examination in the evaluation of HIV patients...
  52. Zhao Y, Navia B, Marra C, Singer E, Chang L, Berger J, et al. Memantine for AIDS dementia complex: open-label report of ACTG 301. HIV Clin Trials. 2010;11:59-67 pubmed publisher
    ..To evaluate the long-term safety and efficacy of memantine use as treatment of HIV-associated cognitive impairment...
  53. Foley J, Ettenhofer M, Wright M, Hinkin C. Emerging issues in the neuropsychology of HIV infection. Curr HIV/AIDS Rep. 2008;5:204-11 pubmed