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Structural gray and white matter changes in patients with HIV

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Abstract

In this cross-sectional study we used magnetic resonance imaging (MRI)-based voxel based morphometry (VBM) in a sample of HIV positive patients to detect structural gray and white matter changes. Forty-eight HIV positive subjects with (n = 28) or without (n = 20) cognitive deficits (mean age 48.5 ± 9.6 years) and 48 age- and sex-matched HIV negative controls underwent MRI for VBM analyses. Clinical testing in HIV patients included the HIV dementia scale (HDS), Unified Parkinson’s Disease Rating Scale (UPDRS) and the grooved pegboard test. Comparing controls with HIV positive patients with cognitive dysfunction (n = 28) VBM showed gray matter decrease in the anterior cingulate and temporal cortices along with white matter reduction in the midbrain region. These changes were more prominent with increasing cognitive decline, when assigning HIV patients to three cognitive groups (not impaired, mildly impaired, overtly impaired) based on performance in the HIV dementia scale. Regression analysis including all HIV positive patients with available data revealed that prefrontal gray matter atrophy in HIV was associated with longer disease duration (n = 48), while motor dysfunction (n = 48) was associated with basal ganglia gray matter atrophy. Lower CD4 cell count (n = 47) correlated with decrease of occipital gray matter. Our results provide evidence for atrophy of nigro-striatal and fronto-striatal circuits in HIV. This pattern of atrophy is consistent with motor dysfunction and dysexecutive syndrome found in HIV patients with HIV-associated neurocognitive disorder.

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References

  1. Everall IP, Luthert PJ, Lantos PL (1993) Neuronal number and volume alterations in the neocortex of HIV infected individuals. J Neurol Neurosurg Psychiatr 56:481–486

    Article  CAS  PubMed  Google Scholar 

  2. Fischer CP, Jorgen G, Gundersen H, Pakkenberg B (1999) Preferential loss of large neocortical neurons during HIV infection: a study of the size distribution of neocortical neurons in the human brain. Brain Res 828:119–126

    Article  CAS  PubMed  Google Scholar 

  3. Adle-Biassette H, Chrétien F, Wingertsmann L, Héry C, Ereau T, Scaravilli F et al (1999) Neuronal apoptosis does not correlate with dementia in HIV infection but is related to microglial activation and axonal damage. Neuropathol Appl Neurobiol 25:123–133

    Article  CAS  PubMed  Google Scholar 

  4. Scaravilli F, Bazille C, Gray F (2007) Neuropathologic contributions to understanding AIDS and the central nervous system. Brain Pathol 17:197–208

    Article  PubMed  Google Scholar 

  5. Stout JC, Ellis RJ, Jernigan TL, Archibald SL, Abramson I, Wolfson T et al (1998) Progressive cerebral volume loss in human immunodeficiency virus infection: a longitudinal volumetric magnetic resonance imaging study. HIV Neurobehavioral Research Center Group. Arch Neurol 55:161–168

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  7. Chiang M, Dutton RA, Hayashi KM, Lopez OL, Aizenstein HJ, Toga AW et al (2007) 3D pattern of brain atrophy in HIV/AIDS visualized using tensor-based morphometry. Neuroimage 34:44–60

    Article  PubMed  Google Scholar 

  8. Thompson PM, Dutton RA, Hayashi KM, Toga AW, Lopez OL, Aizenstein HJ et al (2005) Thinning of the cerebral cortex visualized in HIV/AIDS reflects CD4+ T lymphocyte decline. Proc Natl Acad Sci USA 102:15647–15652

    Article  CAS  PubMed  Google Scholar 

  9. Cardenas V, Meyerhoff D, Studholme C, Kornak J, Rothlind J, Lampiris H et al (2009) Evidence for ongoing brain injury in human immunodeficiency virus-positive patients treated with antiretroviral therapy. J Neurovirol 15:1–10

    Article  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  11. Letendre S, Marquie-Beck J, Capparelli E, Best B, Clifford D, Collier AC et al (2008) Validation of the CNS Penetration-Effectiveness rank for quantifying antiretroviral penetration into the central nervous system. Arch Neurol 65:65–70

    Article  PubMed  Google Scholar 

  12. Tozzi V, Balestra P, Salvatori MF, Vlassi C, Liuzzi G, Giancola ML et al (2009) Changes in cognition during antiretroviral therapy: comparison of 2 different ranking systems to measure antiretroviral drug efficacy on HIV-associated neurocognitive disorders. J Acquir Immune Defic Syndr 52:56–63

    Article  CAS  PubMed  Google Scholar 

  13. Letendre SL, McCutchan JA, Childers ME, Woods SP, Lazzaretto D, Heaton RK et al (2004) Enhancing antiretroviral therapy for human immunodeficiency virus cognitive disorders. Ann Neurol 56:416–423

    Article  PubMed  Google Scholar 

  14. Power C, Selnes OA, Grim JA, McArthur JC (1995) HIV Dementia Scale: a rapid screening test. J Acquir Immune Defic Syndr Hum Retrovirol 8:273–278

    Article  CAS  PubMed  Google Scholar 

  15. Maschke M, Kastrup O, Esser S, Ross B, Hengge U, Hufnagel A (2000) Incidence and prevalence of neurological disorders associated with HIV since the introduction of highly active antiretroviral therapy (HAART). J Neurol Neurosurg Psychiatr 69:376–380

    Article  CAS  PubMed  Google Scholar 

  16. Cysique LA, Brew BJ (2009) Neuropsychological functioning and antiretroviral treatment in HIV/AIDS: a review. Neuropsychol Rev 19:169–185

    Article  PubMed  Google Scholar 

  17. Simioni S, Cavassini M, Annoni J, Rimbault Abraham A, Bourquin I, Schiffer V et al (2010) Cognitive dysfunction in HIV patients despite long-standing suppression of viremia. AIDS 24:1243–1250

    PubMed  Google Scholar 

  18. Ashburner J, Friston KJ (2000) Voxel-based morphometry––the methods. Neuroimage 11:805–821

    Article  CAS  PubMed  Google Scholar 

  19. Good CD, Johnsrude IS, Ashburner J, Henson RN, Friston KJ, Frackowiak RS (2001) A voxel-based morphometric study of ageing in 465 normal adult human brains. Neuroimage 14:21–36

    Article  CAS  PubMed  Google Scholar 

  20. Obermann M, Küper M, Kastrup O, Yaldizli O, Esser S, Thiermann J et al (2009) Substantia nigra hyperechogenicity and CSF dopamine depletion in HIV. J Neurol 256:948–953

    Article  CAS  PubMed  Google Scholar 

  21. Tzourio-Mazoyer N, Landeau B, Papathanassiou D, Crivello F, Etard O, Delcroix N et al (2002) Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage 15:273–289

    Article  CAS  PubMed  Google Scholar 

  22. Ernst T, Yakupov R, Nakama H, Crocket G, Cole M, Watters M et al (2009) Declined neural efficiency in cognitively stable human immunodeficiency virus patients. Ann Neurol 65:316–325

    Article  PubMed  Google Scholar 

  23. Iudicello JE, Woods SP, Parsons TD, Moran LM, Carey CL, Grant I (2007) Verbal fluency in HIV infection: a meta-analytic review. J Int Neuropsychol Soc 13:183–189

    Article  PubMed  Google Scholar 

  24. Woods SP, Carey CL, Tröster AI, Grant I (2005) Action (verb) generation in HIV-1 infection. Neuropsychologia 43:1144–1151

    Article  PubMed  Google Scholar 

  25. Mitchell RLC (2010) Linear increases in BOLD response associated with increasing proportion of incongruent trials across time in a colour Stroop task. Exp Brain Res 203:193–204

    Article  PubMed  Google Scholar 

  26. Chen Y, An H, Zhu H, Stone T, Smith JK, Hall C et al (2009) White matter abnormalities revealed by diffusion tensor imaging in non-demented and demented HIV+ patients. Neuroimage 47:1154–1162

    Article  PubMed  Google Scholar 

  27. White DA, Taylor MJ, Butters N, Mack C, Salmon DP, Peavy G et al (1997) Memory for verbal information in individuals with HIV-associated dementia complex. HNRC Group. J Clin Exp Neuropsychol 19:357–366

    Article  CAS  PubMed  Google Scholar 

  28. Gongvatana A, Woods SP, Taylor MJ, Vigil O, Grant I (2007) Semantic clustering inefficiency in HIV-associated dementia. J Neuropsychiatry Clin Neurosci 19:36–42

    Article  PubMed  Google Scholar 

  29. Berger JR, Arendt G (2000) HIV dementia: the role of the basal ganglia and dopaminergic systems. J Psychopharmacol 14:214–221

    Article  CAS  PubMed  Google Scholar 

  30. Kaiser S, Kopka M, Rentrop M, Walther S, Kronmüller K, Olbrich R et al (2010) Maintenance of real objects and their verbal designations in working memory. Neurosci Lett 469:65–69

    Article  CAS  PubMed  Google Scholar 

  31. Rose M, Haider H, Büchel C (2010) The emergence of explicit memory during learning. Cereb Cortex. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20194687

  32. Thothathiri M, Schwartz MF, Thompson-Schill SL (2010) Selection for position: the role of left ventrolateral prefrontal cortex in sequencing language. Brain Lang 113:28–38

    Article  PubMed  Google Scholar 

  33. Pascal S, Resnick L, Barker WW, Loewenstein D, Yoshii F, Chang JY et al (1991) Metabolic asymmetries in asymptomatic HIV-1 seropositive subjects: relationship to disease onset and MRI findings. J Nucl Med 32:1725–1729

    CAS  PubMed  Google Scholar 

  34. Melrose RJ, Tinaz S, Castelo JMB, Courtney MG, Stern CE (2008) Compromised fronto-striatal functioning in HIV: an fMRI investigation of semantic event sequencing. Behav Brain Res 188:337–347

    Article  PubMed  Google Scholar 

  35. Ances BM, Roc AC, Wang J, Korczykowski M, Okawa J, Stern J et al (2006) Caudate blood flow and volume are reduced in HIV+ neurocognitively impaired patients. Neurology 66:862–866

    Article  CAS  PubMed  Google Scholar 

  36. Kumar AM, Borodowsky I, Fernandez B, Gonzalez L, Kumar M (2007) Human immunodeficiency virus type 1 RNA levels in different regions of human brain: quantification using real-time reverse transcriptase-polymerase chain reaction. J Neurovirol 13:210–224

    Article  CAS  PubMed  Google Scholar 

  37. Kumar AM, Fernandez J, Singer EJ, Commins D, Waldrop-Valverde D, Ownby RL et al (2009) Human immunodeficiency virus type 1 in the central nervous system leads to decreased dopamine in different regions of postmortem human brains. J Neurovirol 15:1–18

    Article  Google Scholar 

  38. Ances BM, Sisti D, Vaida F, Liang CL, Leontiev O, Perthen JE et al (2009) Resting cerebral blood flow: a potential biomarker of the effects of HIV in the brain. Neurology 73:702–708

    Article  CAS  PubMed  Google Scholar 

  39. Banks WA, Robinson SM, Nath A (2005) Permeability of the blood-brain barrier to HIV-1 Tat. Exp Neurol 193:218–227

    Article  CAS  PubMed  Google Scholar 

  40. Cysique LA, Vaida F, Letendre S, Gibson S, Cherner M, Woods SP et al (2009) Dynamics of cognitive change in impaired HIV-positive patients initiating antiretroviral therapy. Neurology 73:342–348

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Michael Küper.

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Küper, M., Rabe, K., Esser, S. et al. Structural gray and white matter changes in patients with HIV. J Neurol 258, 1066–1075 (2011). https://doi.org/10.1007/s00415-010-5883-y

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  • DOI: https://doi.org/10.1007/s00415-010-5883-y

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