Top

Published in:

01-08-2018

Basal ganglia shrinkage without remarkable hippocampal atrophy in chronic aviremic HIV-positive patients

Authors: Tamara Tesic, Jasmina Boban, Mladen Bjelan, Aleksandar Todorovic, Dusko Kozic, Snezana Brkic

Published in: Journal of NeuroVirology | Issue 4/2018

Abstract

Conventional magnetic-resonance (MR) imaging is not sensitive enough in depicting subtle neurodegenerative changes that occur during chronic HIV infection with good peripheral viral suppression. The aim of this study was to compare brain volumes in HIV-positive subjects with age- and education-matched healthy controls with regard to influence of aging and immunologic parameters. An overall of 65 subjects (40 HIV-positive and 25 age-, gender-, and education-matched healthy subjects) underwent conventional MR imaging with three-dimensional sequence adequate for volumetric measurements. Volumes of specific brain regions were measured and compared between HIV-positive and healthy subjects using Student t test. Correlations between obtained brain volumes and immunologic parameters were determined using Pearson’s correlation test. Influence of age as a covariate was determined using ANCOVA test. Statistical value was set at p < 0.05. Volumes of nucleus accumbens (p = 0.003), putamen (p = 0.003), and thalamus (p = 0.046) were significantly decreased in HIV-positive subjects compared with healthy, while volumes of lateral ventricles were significantly increased (p = 0.043). However, influence of age on atrophy was greater than presence of HIV infection in all observed volumes. Positive correlation of nadir CD4+ count and nucleus accumbens volume was obtained, as well as of therapy with lateral ventricle volumes. Volumes of putamen correlated negatively with duration of therapy. HIV-associated atrophic changes are visible in nucleus accumbens, putamen, and thalamus in neurocognitively asymptomatic stage, while no changes can be observed in the hippocampus, affected by other types of dementias. Under therapy, the influence of physiological aging on HIV-associated atrophy is greater than the presence of HIV infection per se.

Ances BM, Ortega M, Vaida F, Heaps J, Paul R (2012) Independent effects of HIV, aging, ad HAART on brain volumetric measures. J Acquir Immune Defic Syndr 59:469–477CrossRefPubMedPubMedCentral

Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M, Clifford DB, Cinque P, Epstein LG, Goodkin K, Gisslen M, Grant I, Heaton RK, Joseph J, Marder K, Marra CM, McArthur JC, Nunn M, Price RW, Pulliam L, Robertson KR, Sacktor N, Valcour V, Wojna VE (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69:1789–1799CrossRefPubMedPubMedCentral

Avci G, Loft S, Sheppard DP, Woods SP, The HIV Neurobehavioral Research Program (HNRP) Group (2016) The effects of HIV disease and older age on laboratory-based, naturalistic, and self-perceived symptoms of prospective memory: does retrieval cue type and delay interval matter? Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 23:716–743CrossRefPubMedPubMedCentral

Becker JT, Maruca V, Kingsley LA et al (2011) Factors affecting brain structure in men with HIV disease in the post-HAART era. Neuroradiology 54:113–121CrossRefPubMedPubMedCentral

Boban J, Kozic D, Turkulov V, Ostojic J, Semnic R, Lendak D, Brkic S (2017a) HIV-associated neurodegeneration and neuroimmunity: multivoxel MR spectroscopy study in drug-naive and treated patients. Eur Radiol 27(10):4218–4236CrossRefPubMed

Boban J, Kozic D, Turkulov V, Lendak D, Bjelan M, Semnic M, Brkic S (2017b) Proton chemical shift imaging study of the combined antiretroviral therapy on Neurometabolic parameters in chronic HIV infection. AJNR Am J Neuroradiol 38(6):1122–1129CrossRefPubMed

Bryant AK, Ellis RJ, Umlauf A, Gouaux B, Soontornniyomkij V, Letendre SL, Achim CL, Masliah E, Grant I, Moore DJ (2015) Antiretroviral therapy reduces neurodegeneration in human immunodeficiency virus infection. AIDS 29:323–330CrossRefPubMedPubMedCentral

Chang L, Andres M, Sadino J, Jiang CS, Nakama H, Miller E, Ernst T (2011) Impact of apolipoprotein E epsilon4 and HIV on cognition and brain atrophy: antagonistic pleiotropy and premature brain aging. NeuroImage 58:1017–1027CrossRefPubMedPubMedCentral

Clifford KM, Samboju V, Cobigo Y, et al (2018) Progressive brain atrophy despite persistent viral suppression in HIV over age 60. J Acquir Immune Defic Syndromes doi:https://doi.org/10.1097/QAI.000001489. (in press)

Cohen RA, Harezlak J, Schifitto G 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 Neuro-Oncol 16:25–32

Cole JH, Underwood J, Caan MWA, de Francesco D, van Zoest R, Leech R, Wit FW, Portegies P, Geurtsen GJ, Schmand BA, Schim van der Loeff M, Franceschi C, Sabin CA, Majoie CB, Winston A, Reiss P, Sharp DJ, COBRA Collaboration (2017) Increased brain-predicted aging in treated HIV disease. Neurology 88(4):1349–1357CrossRefPubMedPubMedCentral

Didic M, Barbeau EJ, Felician O, Tramoni E, Guedj E, Poncet M, Ceccaldi M (2011) Which memory system is impaired first in Alzheimer's disease? J Alzheimers Dis 27(1):11–22CrossRefPubMed

Ellis RJ, Deutsch R, Heaton RK, Marcotte TD, McCutchan JA, Nelson JA, Abramson I, Thal LJ, Atkinson JH, Wallace MR, Grant I (1997) Neurocognitive impairment is an independent risk factor for death in HIV infection. Arch Neurol 54(4):416–424CrossRefPubMed

Ellis RJ, Badiee J, Vaida F, Letendre S, Heaton RK, Clifford D, Collier AC, Gelman B, McArthur J, Morgello S, McCutchan J, Grant I, CHARTER Group (2011) CD4 nadir is a predictor of HIV neurocognitive impairment in the era of combination antiretroviral therapy. AIDS 25(14):1747–1751CrossRefPubMed

Grahn JA, Parkinosn JA, Owen AM (2008) The cognitive functions of the caudate nucleus. Prog Neurobiol 86(3):144–155CrossRef

Heaton RK, Franklin DR, Ellis RJ et al (2011) HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in race, nature and predictors. J Neuro-Oncol 17(1):3–16

Hilal S, Amin SM, Venketasubramanian N, Niessen WJ, Vrooman H, Wong TY, Chen C, Ikram MK (2015) Subcortical atrophy in cognitive impairment and dementia. J Alzheimers Dis 48(3):813–823CrossRefPubMed

Jayadev S, Garden G (2009) Host and viral factors influencing the pathogenesis of HIV-associated neurocognitive disorders. J NeuroImmune Pharmacol 4(2):175–189CrossRefPubMedPubMedCentral

Manjon J, Coupe P (2016) VolBrain: an online MRI brain Volumetry system. Front Neuroinform 10:30–43CrossRefPubMedPubMedCentral

Nie X, Sun Y, Wan S, Zhao H, Liu R, Li X, Wu S, Nedelska Z, Hort J, Qing Z, Xu Y, Zhang B (2017) Subregional structural alterations in hippocampus and nucleus accumbens correlate with the clinical impairment in patients with Alzheimer’s disease clinical spectrum: parallel combining volume and vertex-based approach. Front Neurol 8:399CrossRefPubMedPubMedCentral

Pfefferbaum A, Rosenbloom MJ, Sassoon SA, Kemper CA, Deresinski S, Rohlfing T, Sullivan EV (2012) Regional brain structural dysmorphology in huma immunodeficiency virus infection: effects of acquired immune deficiency syndrome, alcoholism and age. Biol Psychiatry 72:361–370. https://doi.org/10.1016/j.biopsych.2012.02.018 CrossRefPubMedPubMedCentral

Pruessner JC, Li LM, Series W et al (2000) Volumetry of hippocampus and amygdala with high-resolution MRI and three-dimensional analysis software: minimizing the discrepancies between laboratories. Cereb Cortex 10(4):433–442CrossRefPubMed

Raz N, Lindenbrger U, Rodrigue KM et al (2005) Regional brain changes in aging healthy adults: general trends, individual differences and modifiers. Cereb Cortex 15:1676–1689CrossRefPubMed

Rugg MD, Yonelinas AP (2003) Human recognition memory: a cognitive neuroscience perspective. Trends Cogn Sci 7(7):313–319CrossRefPubMed

Salgado S, Kaplitt M, Milchael G (2015) The nuccleus accumbens: a comprehensive review. Stereotact Funct Neurosurg 93(2):75–93CrossRefPubMed

Scott JC, Woods SP, Carey CL et al (2011) Neurocognitive consequences of HIV infection in older adults: an evaluation of the “cortical” hypothesis. AIDS Behav 15:1187–1196CrossRefPubMed

Sheppard DP, Iudicello JE, Morgan EE et al (2017) Accelerated and accentuated neurocognitive aging in HIV infection. J Neuro-Oncol 23:492–500. https://doi.org/10.1007/s13365-017-0523-2 CrossRef

Shikuma CM, Nakamoto B, Shiramizu B, Liang CY, DeGruttola V, Bennett K, Paul R, Kallianpur K, Chow D, Gavegnano C, Hurwitz SJ, Schinazi RF, Valcour VG (2012) Antiretroviral monocyte efficacy score linked to cognitive impairment in HIV. Antivir Ther 17(7):1233–1242CrossRefPubMedPubMedCentral

Tate DF, DeLong A, McCaffrey DE, Kertesz K, Paul RH, Conley J, Russell T, Coop K, Gillani F, Flanigan T, Tashima K, Hogan JW (2011) Recent clinical history and cognitive dysfunction for attention and executive function among human immunodeficiency virus-infected patients. Arch Clin Neuropsychol 26(7):614–623CrossRefPubMedPubMedCentral

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

Towgood KJ, Pirkanen M, Kulasegaram R et al (2012) 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 48:230–241CrossRefPubMed

Tyler IK, Wright P, Randall B et al (2010) Reorganization of syntactic processing following left hemisphere brain damage: does right hemisphere activity preserve function? Brain 133:3396–3408CrossRefPubMedPubMedCentral

Vassalo M, Fabre R, Durant J et al (2017) A decreasing CD4/CD8 ratio over time and lower CSF-penetrating antiretroviral regimens are associated with a higher risk of neurocognitive deterioration, indepently of viral replication. J Neuro-Oncol 23(2):216–225

Yi H-A, Moller C, Dieleman N et al (2016) Relation between subcortical grey matter atrophy and conversion from mild cognitive impairment to Alzheimer’s disease. J Neurol Neurosurg Psychiatry 87(4):425–432CrossRefPubMed

Title: Basal ganglia shrinkage without remarkable hippocampal atrophy in chronic aviremic HIV-positive patients
Authors: Tamara Tesic
Jasmina Boban
Mladen Bjelan
Aleksandar Todorovic
Dusko Kozic
Snezana Brkic
Publication date: 01-08-2018
Publisher: Springer International Publishing
Published in: Journal of NeuroVirology / Issue 4/2018
Print ISSN: 1355-0284
Electronic ISSN: 1538-2443
DOI: https://doi.org/10.1007/s13365-018-0635-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Basal ganglia shrinkage without remarkable hippocampal atrophy in chronic aviremic HIV-positive patients

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2018

Incidence of symptomatic CSF viral escape in HIV infected patients receiving atazanavir/ritonavir (ATV/r)-containing ART: a tertiary care cohort in western India

Cerebrospinal fluid drug concentrations and viral suppression in HIV-1-infected patients receiving ritonavir-boosted atazanavir plus lamivudine dual antiretroviral therapy (Spanish HIV/AIDS Research Network, PreEC/RIS 39)

Does intra-individual neurocognitive variability relate to neuroinvasive disease and quality of life in West Nile Virus?

Ultradeep single-molecule real-time sequencing of HIV envelope reveals complete compartmentalization of highly macrophage-tropic R5 proviral variants in brain and CXCR4-using variants in immune and peripheral tissues

Caspase-1-associated immune activation in an accelerated SIV-infected rhesus macaque model

HTLV-1 myelopathy after renal transplant and antiviral prophylaxis: the need for screening