Skip to main content
Erschienen in: Current HIV/AIDS Reports 1/2019

18.02.2019 | Central Nervous System and Cognition (SS Spudich, Section Editor)

Brain PET Imaging: Value for Understanding the Pathophysiology of HIV-associated Neurocognitive Disorder (HAND)

verfasst von: Sanhita Sinharay, Dima A. Hammoud

Erschienen in: Current HIV/AIDS Reports | Ausgabe 1/2019

Einloggen, um Zugang zu erhalten

Abstract

Purpose of Review

The purpose of this review is to summarize recent developments in PET imaging of neuropathologies underlying HIV-associated neurocognitive dysfunction (HAND). We concentrate on the recent post antiretroviral era (ART), highlighting clinical and preclinical brain PET imaging studies.

Recent Findings

In the post ART era, PET imaging has been used to better understand perturbations of glucose metabolism, neuroinflammation, the function of neurotransmitter systems, and amyloid/tau protein deposition in the brains of HIV-infected patients and HIV animal models. Preclinical and translational findings from those studies shed a new light on the complex pathophysiology underlying HAND.

Summary

The molecular imaging capabilities of PET in neuro-HIV are great complements for structural imaging modalities. Recent and future PET imaging studies can improve our understanding of neuro-HIV and provide biomarkers of disease progress that could be used as surrogate endpoints in the evaluation of the effectiveness of potential neuroprotective therapies.
Literatur
1.
Zurück zum Zitat McArthur JC, Steiner J, Sacktor N, Nath A. Human immunodeficiency virus-associated neurocognitive disorders: mind the gap. Ann Neurol. 2010;67(6):699–714.PubMed McArthur JC, Steiner J, Sacktor N, Nath A. Human immunodeficiency virus-associated neurocognitive disorders: mind the gap. Ann Neurol. 2010;67(6):699–714.PubMed
4.
Zurück zum Zitat Brew BJ. Evidence for a change in AIDS dementia complex in the era of highly active antiretroviral therapy and the possibility of new forms of AIDS dementia complex. AIDS (London, England). 2004;18(Suppl 1):S75–8.CrossRef Brew BJ. Evidence for a change in AIDS dementia complex in the era of highly active antiretroviral therapy and the possibility of new forms of AIDS dementia complex. AIDS (London, England). 2004;18(Suppl 1):S75–8.CrossRef
6.
11.
Zurück zum Zitat Chang L, Wang GJ, Volkow ND, Ernst T, Telang F, Logan J, et al. Decreased brain dopamine transporters are related to cognitive deficits in HIV patients with or without cocaine abuse. NeuroImage. 2008;42(2):869–78.PubMedPubMedCentralCrossRef Chang L, Wang GJ, Volkow ND, Ernst T, Telang F, Logan J, et al. Decreased brain dopamine transporters are related to cognitive deficits in HIV patients with or without cocaine abuse. NeuroImage. 2008;42(2):869–78.PubMedPubMedCentralCrossRef
12.
Zurück zum Zitat Nagano-Saito A, Liu J, Doyon J, Dagher A. Dopamine modulates default mode network deactivation in elderly individuals during the tower of London task. Neurosci Lett. 2009;458(1):1–5.PubMedCrossRef Nagano-Saito A, Liu J, Doyon J, Dagher A. Dopamine modulates default mode network deactivation in elderly individuals during the tower of London task. Neurosci Lett. 2009;458(1):1–5.PubMedCrossRef
18.
Zurück zum Zitat Descamps M, Hyare H, Stebbing J, Winston A. Magnetic resonance imaging and spectroscopy of the brain in HIV disease. J HIV Ther. 2008;13(3):55–8.PubMed Descamps M, Hyare H, Stebbing J, Winston A. Magnetic resonance imaging and spectroscopy of the brain in HIV disease. J HIV Ther. 2008;13(3):55–8.PubMed
26.
Zurück zum Zitat Wiley CA, Lopresti BJ, Becker JT, Boada F, Lopez OL, Mellors J, et al. Positron emission tomography imaging of peripheral benzodiazepine receptor binding in human immunodeficiency virus-infected subjects with and without cognitive impairment. J Neurovirol. 2006;12(4):262–71.PubMedCrossRef Wiley CA, Lopresti BJ, Becker JT, Boada F, Lopez OL, Mellors J, et al. Positron emission tomography imaging of peripheral benzodiazepine receptor binding in human immunodeficiency virus-infected subjects with and without cognitive impairment. J Neurovirol. 2006;12(4):262–71.PubMedCrossRef
27.
Zurück zum Zitat Hammoud DA, Endres CJ, Chander AR, Guilarte TR, Wong DF, Sacktor NC, et al. Imaging glial cell activation with [11C]-R-PK11195 in patients with AIDS. J Neurovirol. 2005;11(4):346–55.PubMedCrossRef Hammoud DA, Endres CJ, Chander AR, Guilarte TR, Wong DF, Sacktor NC, et al. Imaging glial cell activation with [11C]-R-PK11195 in patients with AIDS. J Neurovirol. 2005;11(4):346–55.PubMedCrossRef
28.
Zurück zum Zitat Wang GJ, Chang L, Volkow ND, Telang F, Logan J, Ernst T, et al. Decreased brain dopaminergic transporters in HIV-associated dementia patients. Brain. 2004;127(Pt 11):2452–8.PubMedCrossRef Wang GJ, Chang L, Volkow ND, Telang F, Logan J, Ernst T, et al. Decreased brain dopaminergic transporters in HIV-associated dementia patients. Brain. 2004;127(Pt 11):2452–8.PubMedCrossRef
38.
Zurück zum Zitat Reid W, Sadowska M, Denaro F, Rao S, Foulke J, Hayes N, et al. An HIV-1 transgenic rat that develops HIV-related pathology and immunologic dysfunction. Proc Natl Acad Sci. 2001;98(16):9271–6.PubMedCrossRef Reid W, Sadowska M, Denaro F, Rao S, Foulke J, Hayes N, et al. An HIV-1 transgenic rat that develops HIV-related pathology and immunologic dysfunction. Proc Natl Acad Sci. 2001;98(16):9271–6.PubMedCrossRef
44.
Zurück zum Zitat Lee DE, Reid WC, Ibrahim WG, Peterson KL, Lentz MR, Maric D, et al. Imaging dopaminergic dysfunction as a surrogate marker of neuropathology in a small-animal model of HIV. Mol Imaging. 2014;13:1–10.PubMed Lee DE, Reid WC, Ibrahim WG, Peterson KL, Lentz MR, Maric D, et al. Imaging dopaminergic dysfunction as a surrogate marker of neuropathology in a small-animal model of HIV. Mol Imaging. 2014;13:1–10.PubMed
57.
58.
Zurück zum Zitat Hsu DC, Sunyakumthorn P, Wegner M, Schuetz A, Silsorn D, Estes JD, et al. Central nervous system inflammation and infection during early, nonaccelerated simian-human immunodeficiency virus infection in rhesus macaques. J Virol. 2018;92(11). https://doi.org/10.1128/jvi.00222-18. Hsu DC, Sunyakumthorn P, Wegner M, Schuetz A, Silsorn D, Estes JD, et al. Central nervous system inflammation and infection during early, nonaccelerated simian-human immunodeficiency virus infection in rhesus macaques. J Virol. 2018;92(11). https://​doi.​org/​10.​1128/​jvi.​00222-18.
65.
Zurück zum Zitat Wallace M, Pyzalski R, Horejsh D, Brown C, Djavani M, Lu Y, et al. Whole body positron emission tomography imaging of activated lymphoid tissues during acute simian-human immunodeficiency virus 89.6PD infection in rhesus macaques. Virology. 2000;274(2):255–61.PubMedCrossRef Wallace M, Pyzalski R, Horejsh D, Brown C, Djavani M, Lu Y, et al. Whole body positron emission tomography imaging of activated lymphoid tissues during acute simian-human immunodeficiency virus 89.6PD infection in rhesus macaques. Virology. 2000;274(2):255–61.PubMedCrossRef
66.
Zurück zum Zitat Scharko AM, Perlman SB, PWN H, Hanson JM, Uno H, Pauza CD. Whole body positron emission tomography imaging of simian immunodeficiency virus-infected rhesus macaques. Proc Natl Acad Sci U S A. 1996;93(13):6425–30.PubMedPubMedCentralCrossRef Scharko AM, Perlman SB, PWN H, Hanson JM, Uno H, Pauza CD. Whole body positron emission tomography imaging of simian immunodeficiency virus-infected rhesus macaques. Proc Natl Acad Sci U S A. 1996;93(13):6425–30.PubMedPubMedCentralCrossRef
67.
Zurück zum Zitat Schreiber-Stainthorp W, Srinivasula S, Sinharay S, Shah S, Wang J, Dodd LE, et al., editors. Brain 18F-FDG PET of SIV-infected macaques after treatment interruption or initiation. Boston: CROI; 2018. Schreiber-Stainthorp W, Srinivasula S, Sinharay S, Shah S, Wang J, Dodd LE, et al., editors. Brain 18F-FDG PET of SIV-infected macaques after treatment interruption or initiation. Boston: CROI; 2018.
68.
Zurück zum Zitat Rottenberg DA, Sidtis JJ, Strother SC, Schaper KA, Anderson JR, Nelson MJ, et al. Abnormal cerebral glucose metabolism in HIV-1 seropositive subjects with and without dementia. J Nucl Med. 1996;37(7):1133–41.PubMed Rottenberg DA, Sidtis JJ, Strother SC, Schaper KA, Anderson JR, Nelson MJ, et al. Abnormal cerebral glucose metabolism in HIV-1 seropositive subjects with and without dementia. J Nucl Med. 1996;37(7):1133–41.PubMed
70.
Zurück zum Zitat von Giesen HJ, Antke C, Hefter H, Wenserski F, Seitz RJ, Arendt G. Potential time course of human immunodeficiency virus type 1-associated minor motor deficits: electrophysiologic and positron emission tomography findings. Arch Neurol. 2000;57(11):1601–7. von Giesen HJ, Antke C, Hefter H, Wenserski F, Seitz RJ, Arendt G. Potential time course of human immunodeficiency virus type 1-associated minor motor deficits: electrophysiologic and positron emission tomography findings. Arch Neurol. 2000;57(11):1601–7.
75.
Zurück zum Zitat Boven LA. Macrophages and HIV-1-associated dementia. Arch Immunol Ther Exp. 2000;48(4):273–9. Boven LA. Macrophages and HIV-1-associated dementia. Arch Immunol Ther Exp. 2000;48(4):273–9.
76.
Zurück zum Zitat Minagar A, Shapshak P, Fujimura R, Ownby R, Heyes M, Eisdorfer C. The role of macrophage/microglia and astrocytes in the pathogenesis of three neurologic disorders: HIV-associated dementia, Alzheimer disease, and multiple sclerosis. J Neurol Sci. 2002;202(1–2):13–23.PubMedCrossRef Minagar A, Shapshak P, Fujimura R, Ownby R, Heyes M, Eisdorfer C. The role of macrophage/microglia and astrocytes in the pathogenesis of three neurologic disorders: HIV-associated dementia, Alzheimer disease, and multiple sclerosis. J Neurol Sci. 2002;202(1–2):13–23.PubMedCrossRef
77.
Zurück zum Zitat Bartels AL, Leenders KL. Neuroinflammation in the pathophysiology of Parkinson’s disease: evidence from animal models to human in vivo studies with [11C]-PK11195 PET. Mov Disord. 2007;22(13):1852–6.PubMedCrossRef Bartels AL, Leenders KL. Neuroinflammation in the pathophysiology of Parkinson’s disease: evidence from animal models to human in vivo studies with [11C]-PK11195 PET. Mov Disord. 2007;22(13):1852–6.PubMedCrossRef
79.
Zurück zum Zitat Tai YF, Pavese N, Gerhard A, Tabrizi SJ, Barker RA, Brooks DJ, et al. Microglial activation in presymptomatic Huntington’s disease gene carriers. Brain. 2007;130(Pt 7):1759–66.PubMedCrossRef Tai YF, Pavese N, Gerhard A, Tabrizi SJ, Barker RA, Brooks DJ, et al. Microglial activation in presymptomatic Huntington’s disease gene carriers. Brain. 2007;130(Pt 7):1759–66.PubMedCrossRef
80.
Zurück zum Zitat Endres CJ, Pomper MG, James M, Uzuner O, Hammoud DA, Watkins CC, et al. Initial evaluation of 11C-DPA-713, a novel TSPO PET ligand, in humans. J Nucl Med. 2009;50(8):1276–82.PubMedPubMedCentralCrossRef Endres CJ, Pomper MG, James M, Uzuner O, Hammoud DA, Watkins CC, et al. Initial evaluation of 11C-DPA-713, a novel TSPO PET ligand, in humans. J Nucl Med. 2009;50(8):1276–82.PubMedPubMedCentralCrossRef
81.
Zurück zum Zitat Chauveau F, Van Camp N, Dolle F, Kuhnast B, Hinnen F, Damont A, et al. Comparative evaluation of the translocator protein radioligands 11C-DPA-713, 18F-DPA-714, and 11C-PK11195 in a rat model of acute neuroinflammation. J Nucl Med. 2009;50(3):468–76.PubMedCrossRef Chauveau F, Van Camp N, Dolle F, Kuhnast B, Hinnen F, Damont A, et al. Comparative evaluation of the translocator protein radioligands 11C-DPA-713, 18F-DPA-714, and 11C-PK11195 in a rat model of acute neuroinflammation. J Nucl Med. 2009;50(3):468–76.PubMedCrossRef
83.
Zurück zum Zitat Nath A, Anderson C, Jones M, Maragos W, Booze R, Mactutus C, et al. Neurotoxicity and dysfunction of dopaminergic systems associated with AIDS dementia. J Psychopharmacol (Oxford, England). 2000;14(3):222–7.CrossRef Nath A, Anderson C, Jones M, Maragos W, Booze R, Mactutus C, et al. Neurotoxicity and dysfunction of dopaminergic systems associated with AIDS dementia. J Psychopharmacol (Oxford, England). 2000;14(3):222–7.CrossRef
84.
Zurück zum Zitat Marcario JK, Manaye KF, SantaCruz KS, Mouton PR, Berman NE, Cheney PD. Severe subcortical degeneration in macaques infected with neurovirulent simian immunodeficiency virus. J Neurovirol. 2004;10(6):387–99.PubMedCrossRef Marcario JK, Manaye KF, SantaCruz KS, Mouton PR, Berman NE, Cheney PD. Severe subcortical degeneration in macaques infected with neurovirulent simian immunodeficiency virus. J Neurovirol. 2004;10(6):387–99.PubMedCrossRef
91.
Zurück zum Zitat Cannon DM, Ichise M, Rollis D, Klaver JM, Gandhi SK, Charney DS, et al. Elevated serotonin transporter binding in major depressive disorder assessed using positron emission tomography and [11C]DASB; comparison with bipolar disorder. Biol Psychiatry. 2007;62(8):870–7.PubMedCrossRef Cannon DM, Ichise M, Rollis D, Klaver JM, Gandhi SK, Charney DS, et al. Elevated serotonin transporter binding in major depressive disorder assessed using positron emission tomography and [11C]DASB; comparison with bipolar disorder. Biol Psychiatry. 2007;62(8):870–7.PubMedCrossRef
92.
Zurück zum Zitat Bhagwagar Z, Murthy N, Selvaraj S, Hinz R, Taylor M, Fancy S, et al. 5-HTT binding in recovered depressed patients and healthy volunteers: a positron emission tomography study with [11C]DASB. Am J Psychiatry. 2007;164(12):1858–65.PubMedCrossRef Bhagwagar Z, Murthy N, Selvaraj S, Hinz R, Taylor M, Fancy S, et al. 5-HTT binding in recovered depressed patients and healthy volunteers: a positron emission tomography study with [11C]DASB. Am J Psychiatry. 2007;164(12):1858–65.PubMedCrossRef
93.
Zurück zum Zitat Meyer JH, Houle S, Sagrati S, Carella A, Hussey DF, Ginovart N, et al. Brain serotonin transporter binding potential measured with carbon 11-labeled DASB positron emission tomography: effects of major depressive episodes and severity of dysfunctional attitudes. Arch Gen Psychiatry. 2004;61(12):1271–9.PubMedCrossRef Meyer JH, Houle S, Sagrati S, Carella A, Hussey DF, Ginovart N, et al. Brain serotonin transporter binding potential measured with carbon 11-labeled DASB positron emission tomography: effects of major depressive episodes and severity of dysfunctional attitudes. Arch Gen Psychiatry. 2004;61(12):1271–9.PubMedCrossRef
94.
Zurück zum Zitat Shah S, Sinharay S, Lee D, Reid WC, Wakim P, Matsuda K, et al., editors. Longitudinal PET imaging of the serotonergic system in SIV-infected nonhuman primates. Boston: CROI; 2018. Shah S, Sinharay S, Lee D, Reid WC, Wakim P, Matsuda K, et al., editors. Longitudinal PET imaging of the serotonergic system in SIV-infected nonhuman primates. Boston: CROI; 2018.
95.
Zurück zum Zitat An SF, Giometto B, Groves M, Miller RF, Beckett AA, Gray F, et al. Axonal damage revealed by accumulation of beta-APP in HIV-positive individuals without AIDS. J Neuropathol Exp Neurol. 1997;56(11):1262–8.PubMedCrossRef An SF, Giometto B, Groves M, Miller RF, Beckett AA, Gray F, et al. Axonal damage revealed by accumulation of beta-APP in HIV-positive individuals without AIDS. J Neuropathol Exp Neurol. 1997;56(11):1262–8.PubMedCrossRef
98.
Zurück zum Zitat Green DA, Masliah E, Vinters HV, Beizai P, Moore DJ, Achim CL. Brain deposition of beta-amyloid is a common pathologic feature in HIV positive patients. AIDS (London, England). 2005;19(4):407–11.CrossRef Green DA, Masliah E, Vinters HV, Beizai P, Moore DJ, Achim CL. Brain deposition of beta-amyloid is a common pathologic feature in HIV positive patients. AIDS (London, England). 2005;19(4):407–11.CrossRef
108.
Zurück zum Zitat Rempel HC, Pulliam L. HIV-1 Tat inhibits neprilysin and elevates amyloid beta. AIDS (London, England). 2005;19(2):127–35.CrossRef Rempel HC, Pulliam L. HIV-1 Tat inhibits neprilysin and elevates amyloid beta. AIDS (London, England). 2005;19(2):127–35.CrossRef
110.
Zurück zum Zitat Stanley LC, Mrak RE, Woody RC, Perrot LJ, Zhang S, Marshak DR, et al. Glial cytokines as neuropathogenic factors in HIV infection: pathogenic similarities to Alzheimer’s disease. J Neuropathol Exp Neurol. 1994;53(3):231–8.PubMedCrossRef Stanley LC, Mrak RE, Woody RC, Perrot LJ, Zhang S, Marshak DR, et al. Glial cytokines as neuropathogenic factors in HIV infection: pathogenic similarities to Alzheimer’s disease. J Neuropathol Exp Neurol. 1994;53(3):231–8.PubMedCrossRef
Metadaten
Titel
Brain PET Imaging: Value for Understanding the Pathophysiology of HIV-associated Neurocognitive Disorder (HAND)
verfasst von
Sanhita Sinharay
Dima A. Hammoud
Publikationsdatum
18.02.2019
Verlag
Springer US
Erschienen in
Current HIV/AIDS Reports / Ausgabe 1/2019
Print ISSN: 1548-3568
Elektronische ISSN: 1548-3576
DOI
https://doi.org/10.1007/s11904-019-00419-8

Weitere Artikel der Ausgabe 1/2019

Current HIV/AIDS Reports 1/2019 Zur Ausgabe

Behavioral Bio-Medical Interface (JL Brown and RJ DiClemente, Section Editors)

Medications for Treatment of Opioid Use Disorder among Persons Living with HIV

Central Nervous System and Cognition (SS Spudich, Section Editor)

HIV Eradication Strategies: Implications for the Central Nervous System

Central Nervous System and Cognition (SS Spudich, Section Editor)

HIV, Depression, and Cognitive Impairment in the Era of Effective Antiretroviral Therapy

The Science of Prevention (JD Stekler and JM Baeten, Section Editors)

HIV Prevention Interventions for Adolescents

Behavioral Bio-Medical Interface (JL Brown and RJ DiClemente, Section Editors)

Interventions to Reduce Drug Use Among Methamphetamine Users at Risk for HIV

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Triglyzeridsenker schützt nicht nur Hochrisikopatienten

10.05.2024 Hypercholesterinämie Nachrichten

Patienten mit Arteriosklerose-bedingten kardiovaskulären Erkrankungen, die trotz Statineinnahme zu hohe Triglyzeridspiegel haben, profitieren von einer Behandlung mit Icosapent-Ethyl, und zwar unabhängig vom individuellen Risikoprofil.

Gibt es eine Wende bei den bioresorbierbaren Gefäßstützen?

In den USA ist erstmals eine bioresorbierbare Gefäßstütze – auch Scaffold genannt – zur Rekanalisation infrapoplitealer Arterien bei schwerer PAVK zugelassen worden. Das markiert einen Wendepunkt in der Geschichte dieser speziellen Gefäßstützen.

Vorsicht, erhöhte Blutungsgefahr nach PCI!

10.05.2024 Koronare Herzerkrankung Nachrichten

Nach PCI besteht ein erhöhtes Blutungsrisiko, wenn die Behandelten eine verminderte linksventrikuläre Ejektionsfraktion aufweisen. Das Risiko ist umso höher, je stärker die Pumpfunktion eingeschränkt ist.

Wie managen Sie die schmerzhafte diabetische Polyneuropathie?

10.05.2024 DDG-Jahrestagung 2024 Kongressbericht

Mit Capsaicin-Pflastern steht eine neue innovative Therapie bei schmerzhafter diabetischer Polyneuropathie zur Verfügung. Bei therapierefraktären Schmerzen stellt die Hochfrequenz-Rückenmarkstimulation eine adäquate Option dar.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.