Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Konkret geht es um den Diabetes-Patienten mit kardiovaskulären Erkrankungen oder Risiken, die Herzinsuffizienz sowie die kardiovaskuläre Primär- und Sekundärprävention. Sind Sie hier schon auf dem neuesten Stand? Unsere Experten beleuchten, wo und warum das bisherige Procedere geändert werden soll und was in der Praxis sinnvoll ist. Holen Sie sich Ihr Update und 2 CME-Punkte beim MMW-Webinar am 24. April von 17.30 bis 19 Uhr. 
Erweiterte Suche
Anmelden
nach oben
Current HIV/AIDS Reports
Erschienen in: Current HIV/AIDS Reports 4/2017

05.08.2017 | Central Nervous System and Cognition (SS Spudich, Section Editor)

Differentiating HIV-Associated Neurocognitive Disorders From Alzheimer’s Disease: an Emerging Issue in Geriatric NeuroHIV

verfasst von: Benedetta Milanini, Victor Valcour

Erschienen in: Current HIV/AIDS Reports | Ausgabe 4/2017

Einloggen, um Zugang zu erhalten

Abstract

Purpose of Review

The purpose of this review was to examine characteristics that may distinguish HIV-associated neurocognitive disorder (HAND) from early Alzheimer’s disease (AD).

Recent Findings

Cerebrospinal fluid (CSF) AD biomarkers are perturbed in HIV, yet these alterations may be limited to settings of advanced dementia or unsuppressed plasma HIV RNA. Neuropsychological testing will require extensive batteries to maximize utility. Structural imaging is limited for early AD detection in the setting of HIV, but proper studies are absent. While positron-emission tomography (PET) amyloid imaging has altered the landscape of differential diagnosis for age-associated neurodegenerative disorders, costs are prohibitive.

Summary

Risk for delayed AD diagnosis in the aging HIV-infected population is now among the most pressing issues in geriatric neuroHIV. While clinical, imaging, and biomarker characterizations of AD are extensively defined, fewer data define characteristics of HIV-associated neurocognitive disorder in the setting of suppressed plasma HIV RNA. Data needed to inform the phenotype of AD in the setting of HIV are equally few.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
2.
Valcour V, et al. Aging exacerbates extrapyramidal motor signs in the era of highly active antiretroviral therapy. J Neuro-Oncol. 2008;14(5):362–7.
3.
DeVaughn S, et al. Aging with HIV-1 infection: motor functions, cognition, and attention—a comparison with Parkinson’s disease. Neuropsychol Rev. 2015;25(4):424–38.
4.
5.
•• Turner R, et al. An individual with human immunodeficiency virus, dementia, and central nervous system amyloid deposition. Alzheimer Dis Assoc Disord. 2016;4:1–5. A case study on a 71-year-old HIV-infected man with a mixed AD/HAND diagnosis. In this case CSF biomarkers were not helpful for AD diagnosis, showing decreased amyloid, increased tau and decreased p-tau.
6.
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(2):200–12.CrossRefPubMed
7.
Becker JT, et al. Prevalence of cognitive disorders differs as a function of age in HIV virus infection. AIDS. 2004;18(Suppl 1):S11–8.CrossRefPubMed
8.
Heaton RK, et al. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology. 2010;75(23):2087–96.CrossRefPubMedPubMedCentral
9.
Simioni S, et al. Cognitive dysfunction in HIV patients despite long-standing suppression of viremia. AIDS. 2010;24(9):1243–50.PubMed
10.
Nightingale S, et al. Controversies in HIV-associated neurocognitive disorders. Lancet Neurol. 2014;13(11):1139–51.
11.
Milanini B, et al. Cognitive reserve and neuropsychological functioning in older HIV-infected people. J Neuro-Oncol. 2016;22(5):575–83.
12.
13.
Heaton RK, et al. HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neuro-Oncol. 2011;17(1):3–16.
14.
• Saylor D, et al. HIV-associated neurocognitive disorder—pathogenesis and prospects for treatment. Nat Rev Neurol. 2016;12(5):309. This is a comprehensive review on the clinical features, epidemiology and neuropathogenesis of HAND. It also presents a number of critical and open questions that need to be addressed in future studies.
15.
Rosen HJ, et al. Metacognition in the behavioral variant of frontotemporal dementia and Alzheimer’s disease. Neuropsychology. 2014;28(3):436–47.CrossRefPubMedPubMedCentral
16.
Chiao S, et al. Deficits in self-awareness impact the diagnosis of asymptomatic neurocognitive impairment in HIV. AIDS Res Hum Retrovir. 2013;29(6):949–56.CrossRefPubMedPubMedCentral
17.
Robertson K, Liner J, Meeker RB. Antiretroviral neurotoxicity. J Neuro-Oncol. 2012;18(5):388–99.
18.
Clifford K, et al. Progressive brain atrophy despite persistent viral suppression in HIV over age 60. JAIDS. 2017; (in press).
19.
• Gelman BB. Neuropathology of HAND with suppressive antiretroviral therapy: encephalitis and neurodegeneration reconsidered. Curr HIV/AIDS Rep. 2015;12(2):272–9. This is a very useful review article on the need for a re-examination of the pathological mechanisms in the era of viral suppression.
20.
21.
Solomon IH, et al. Brain and liver pathology, amyloid deposition, and interferon responses among older HIV-positive patients in the late HAART era. BMC Infect Dis. 2017;17(1):151.CrossRefPubMedPubMedCentral
22.
23.
24.
Rempel HC, Pulliam L. HIV-1 Tat inhibits neprilysin and elevates amyloid beta. AIDS. 2005;19(2):127–35.CrossRefPubMed
25.
26.
Green DA, et al. Brain deposition of beta-amyloid is a common pathologic feature in HIV positive patients. AIDS. 2005;19(4):407–11.CrossRefPubMed
27.
Anthony IC, et al. Accelerated Tau deposition in the brains of individuals infected with human immunodeficiency virus-1 before and after the advent of highly active anti-retroviral therapy. Acta Neuropathol. 2006;111(6):529–38.CrossRefPubMed
28.
Gelman BB, Schuenke K. Brain aging in acquired immunodeficiency syndrome: increased ubiquitin-protein conjugate is correlated with decreased synaptic protein but not amyloid plaque accumulation. J Neuro-Oncol. 2004;10(2):98–108.
29.
30.
Khanlou N, et al. Increased frequency of alpha-synuclein in the substantia nigra in human immunodeficiency virus infection. J Neuro-Oncol. 2009;15(2):131–8.
31.
• Ortega M, Ances BM. Role of HIV in amyloid metabolism. J NeuroImmune Pharmacol. 2014;9(4):483–91. This work offers a broad overview of the multiple steps in the amyloid pathway that are disrupted by HIV as measured by CSF biomarkers and amyloid PET imaging.
32.
Andras IE, Toborek M. Amyloid beta accumulation in HIV-1-infected brain: the role of the blood brain barrier. IUBMB Life. 2013;65(1):43–9.CrossRefPubMed
33.
Mocchetti I, et al. Human immunodeficiency virus-associated dementia: a link between accumulation of viral proteins and neuronal degeneration. Curr Trends Neurol. 2014;8:71–85.PubMedPubMedCentral
34.
35.
•• Peterson J, et al. Cerebrospinal fluid (CSF) neuronal biomarkers across the spectrum of HIV infection: hierarchy of injury and detection. PLoS One. 2014;9(12):e116081. This study shows change in 6 CSF neuronal biomarkers according to different stages of HIV-infection and immunosuppression. It proposes a hierarchical model of progression to severe HIV-related CNS injury reflected by specific changes in CSF biomarkers. Given the cross-sectional study design, future longitudinal studies might be most valuable in better informing the evolving neuropathology over the course of HIV-infection.
36.
37.
Kim J, Yoon JH, Kim YS. HIV-1 Tat interacts with and regulates the localization and processing of amyloid precursor protein. PLoS One. 2013;8(11):e77972.CrossRefPubMedPubMedCentral
38.
Chen X, Hui L, Geiger NH, Haughey NJ, Geiger JD. Endolysosome involvement in HIV-1 transactivator protein-induced neuronal amyloid beta production. Neurobiol Aging. 2013;34(10):2370–8.CrossRefPubMedPubMedCentral
39.
40.
Valcour V, et al. Age, apolipoprotein E4, and the risk of HIV dementia: the Hawaii Aging with HIV Cohort. J Neuroimmunol. 2004;157(1–2):197–202.CrossRefPubMed
41.
Nir TM, et al. Mapping white matter integrity in elderly people with HIV. Hum Brain Mapp. 2014;35(3):975–92.CrossRefPubMed
42.
Wendelken L, Jahanshad N, Rosen H, Busovaca E, Allen I, Coppola G, et al. ApoE e4 is associated with cognition, brain integrity, and atrophy in HIV over age 60. J Acquir Immune Defic Syndr. 2016;73(4):426–32.
43.
Cysique LA, et al. APOE epsilon4 moderates abnormal CSF-abeta-42 levels, while neurocognitive impairment is associated with abnormal CSF tau levels in HIV+ individuals - a cross-sectional observational study. BMC Neurol. 2015;15:51.CrossRefPubMedPubMedCentral
44.
Soontornniyomkij V, Moore DJ, Gouaux B, Soontornniyomkij B, Tatro ET, Umlauf A, et al. Cerebral β-amyloid deposition predicts HIV-associated neurocognitive disorders in APOE ε4 carriers. AIDS. 2012;26(18):2327–35.
45.
•• Vera JH, et al. Neuroinflammation in treated HIV-positive individuals: a TSPO PET study. Neurology. 2016;86(15):1425–32. This study provides insight into the pathology of HAND in the era of suppressed plasma virus, showing in vivo neuroinflammation in cognitively normal HIV-infected individuals on effective cART with suppressed plasma virus.
46.
Kreisl WC, et al. (11)C-PBR28 binding to translocator protein increases with progression of Alzheimer’s disease. Neurobiol Aging. 2016;44:53–61.CrossRefPubMedPubMedCentral
47.
Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004;256(3):183–94.CrossRefPubMed
48.
Sheppard DP, et al. Elevated rates of mild cognitive impairment in HIV disease. J Neuro-Oncol. 2015;21(5):576–84.
49.
•• Makitalo S, et al. The cerebrospinal fluid biomarker profile in an HIV-infected subject with Alzheimer’s disease. AIDS Res Ther. 2015;12:23. A case study on a 63-year-old HIV-infected woman eventually noted to have a clinical history, neuropsychological profile and CSF biomarkers consistent with AD.
50.
51.
Brouillette MJ, et al. Identifying neurocognitive decline at 36 months among HIV-positive participants in the CHARTER cohort using group-based trajectory analysis. PLoS One. 2016;11(5):e0155766.CrossRefPubMedPubMedCentral
52.
53.
54.
Cysique LA, Maruff P, Brew BJ. Prevalence and pattern of neuropsychological impairment in human immunodeficiency virus-infected/acquired immunodeficiency syndrome (HIV/AIDS) patients across pre- and post-highly active antiretroviral therapy eras: a combined study of two cohorts. J Neuro-Oncol. 2004;10(6):350–7.
55.
Scott JC, et al. Neurocognitive consequences of HIV infection in older adults: an evaluation of the “cortical” hypothesis. AIDS Behav. 2011;15(6):1187–96.CrossRefPubMed
56.
Ciccarelli N, et al. Verbal list learning and memory profiles in HIV-infected adults, Alzheimer’s disease, and Parkinson’s disease: an evaluation of the “cortical hypothesis” of NeuroAIDS. Appl Neuropsychol Adult. 2016;1–10. doi:10.​1080/​23279095.​2016.​1189424
57.
Milanini BAI, Javandel S, Joanna H, Paul R, Valcour V. Discriminant analysis of neuropsychological testing differentiates HIV-associated neurocognitive disorder from mild cognitive impairment due to Alzheimer’s disease. Toronto: International Society of NeuroVirology; 2016. p. 25–8.
58.
Ances BM, Ellis RJ. Dementia and neurocognitive disorders due to HIV-1 infection. Semin Neurol. 2007;27(1):86–92.CrossRefPubMed
59.
Tarawneh R, Holtzman DM. The clinical problem of symptomatic Alzheimer disease and mild cognitive impairment. Cold Spring Harb Perspect Med. 2012;2(5):a006148.CrossRefPubMedPubMedCentral
60.
61.
Milanini B, et al. Psychiatric symptom burden in older people living with HIV with and without cognitive impairment: the UCSF HIV over 60 cohort study. AIDS Care. 2017;29(9);1178-85.
62.
Mega MS, et al. The spectrum of behavioral changes in Alzheimer’s disease. Neurology. 1996;46(1):130–5.CrossRefPubMed
63.
64.
FM M, et al. Prevalence of neuropsychiatric symptoms in mild cognitive impairment and Alzheimer’s disease, and its relationship with cognitive impairment. Curr Alzheimer Res. 2010;7(6):517–26.CrossRef
65.
Boublay N, Schott AM, Krolak-Salmon P. Neuroimaging correlates of neuropsychiatric symptoms in Alzheimer’s disease: a review of 20 years of research. Eur J Neurol. 2016;23(10):1500–9.CrossRefPubMed
66.
Krut JJ, Price R., Zetterberg H, Fuchs D, Hagberg L, Yilmaz A, Cinque P, Nilsson S, Gisslén M. No support for premature central nervous system aging in HIV-1 when measured by cerebrospinal fluid phosphorylated tau (p-tau). Virulence. 2016;19:1-6.
67.
Brew BJ, et al. CSF amyloid beta42 and tau levels correlate with AIDS dementia complex. Neurology. 2005;65(9):1490–2.CrossRefPubMed
68.
Peluso MJ, et al. Cerebrospinal fluid and neuroimaging biomarker abnormalities suggest early neurological injury in a subset of individuals during primary HIV infection. J Infect Dis. 2013;207(11):1703–12.CrossRefPubMedPubMedCentral
69.
Krut JJ, et al. Cerebrospinal fluid Alzheimer’s biomarker profiles in CNS infections. J Neurol. 2013;260(2):620–6.CrossRefPubMed
70.
Krut JJ, Mellberg T, Price RW, Hagberg L, Fuchs D, Rosengren L, et al. Biomarker evidence of axonal injury in neuroasymptomatic HIV-1 patients. PLoS One. 2014;9(2):e88591.
71.
Gisslen M, et al. Plasma concentration of the neurofilament light protein (NFL) is a biomarker of CNS injury in HIV infection: a cross-sectional study. EBioMedicine. 2016;3:135–40.CrossRefPubMed
72.
Zetterberg H, et al. Association of cerebrospinal fluid neurofilament light concentration with Alzheimer disease progression. JAMA Neurol. 2016;73(1):60–7.CrossRefPubMed
73.
Gongvatana A, et al. White matter tract injury and cognitive impairment in human immunodeficiency virus-infected individuals. J Neuro-Oncol. 2009;15(2):187–95.
74.
Thompson PM, et al. Thinning of the cerebral cortex visualized in HIV/AIDS reflects CD4+ T lymphocyte decline. Proc Natl Acad Sci U S A. 2005;102(43):15647–52.CrossRefPubMedPubMedCentral
75.
Klunder AD, Chiang M, Dutton RA, Lee SE, Toga AW, Lopez OL, et al. Mapping cerebellar degeneration in HIV/AIDS. Neuroreport. 2008;19(17):1655–9.
76.
Pfefferbaum A, et al. Regional brain structural dysmorphology in human immunodeficiency virus infection: effects of acquired immune deficiency syndrome, alcoholism, and age. Biol Psychiatry. 2012;72(5):361–70.CrossRefPubMedPubMedCentral
77.
Kallianpur KJ, et al. Peripheral blood HIV DNA is associated with atrophy of cerebellar and subcortical gray matter. Neurology. 2013;80(19):1792–9.CrossRefPubMedPubMedCentral
78.
McMurtray A, et al. Small-vessel vascular disease in human immunodeficiency virus infection: the Hawaii aging with HIV cohort study. Cerebrovasc Dis. 2007;24(2–3):236–41.CrossRefPubMed
79.
Jernigan TL, et al. Clinical factors related to brain structure in HIV: the CHARTER study. J Neuro-Oncol. 2011;17(3):248–57.
80.
81.
Becker JT, et al. Factors affecting brain structure in men with HIV disease in the post-HAART era. Neuroradiology. 2012;54(2):113–21.CrossRefPubMed
82.
Clark US, Cohen RA. Brain dysfunction in the era of combination antiretroviral therapy: implications for the treatment of the aging population of HIV-infected individuals. Curr Opin Investig Drugs. 2010;11(8):884–900.PubMedPubMedCentral
83.
Pini L, et al. Brain atrophy in Alzheimer’s disease and aging. Ageing Res Rev. 2016;30:25–48.CrossRefPubMed
84.
• Zhang Y, et al. Extracting patterns of morphometry distinguishing HIV associated neurodegeneration from mild cognitive impairment via group cardinality constrained classification. Hum Brain Mapp. 2016;37(12):4523–38. This study employed machine learning technology to differentiate HAND from Mild Cognitive Impairment (MCI) due to Alzheimer’s Disease (AD) and found that 8 brain regions were able to distinguish the two with 90% accuracy. Future studies are needed to validate these findings.
85.
Soontornniyomkij V, et al. HIV protease inhibitor exposure predicts cerebral small vessel disease. AIDS. 2014;28(9):1297-306.
86.
Watson C, et al. White matter hyperintensities correlate to cognition and fiber tract integrity in older adults with HIV. J Neuro-Oncol. 2017;23(3):422–9.
87.
Su T, et al. White matter structure alterations in HIV-1-infected men with sustained suppression of viraemia on treatment. AIDS. 2016;30(2):311–22.CrossRefPubMed
88.
• Underwood J, et al. Grey and white matter abnormalities in treated HIV-disease and their relationship to cognitive function. Clin Infect Dis. 2017. doi:10.​1093/​cid/​cix301. By using machine learning approach to combine cognitive, diffusion and volumetric data this study found widespread white matter abnormalities that correlated with cognitive impairment among successfully treated HIV-infected patients.
89.
Chen Y, et al. White matter abnormalities revealed by diffusion tensor imaging in non-demented and demented HIV+ patients. NeuroImage. 2009;47(4):1154–62.CrossRefPubMedPubMedCentral
90.
91.
92.
• Ances BM, et al. 11C-PiB imaging of human immunodeficiency virus-associated neurocognitive disorder. Arch Neurol. 2012;69(1):72–7. A study of 11C-PiB in HIV-infected individuals that found no increased 11C-PiB binding in cognitively impaired patients, suggesting that 11C-PiB may help differentiate HAND from AD.
93.
Ances BM, Morris CJ, Teshome M, Taylor J, Xiong C, Aldea P, et al. Cognitively unimpaired HIV-positive subjects do not have increased 11C-PiB: a case-control study. Neurology. 2010;75(2):111–5.
94.
Sathekge M, McFarren A, Dadachova E. Role of nuclear medicine in neuroHIV: PET, SPECT, and beyond. Nucl Med Commun. 2014;35(8):792–6.PubMedPubMedCentral
95.
Ishii K. PET approaches for diagnosis of dementia. AJNR Am J Neuroradiol. 2014;35(11):2030–8.CrossRefPubMed
96.
Vera JH, et al. PET brain imaging in HIV-associated neurocognitive disorders (HAND) in the era of combination antiretroviral therapy. Eur J Nucl Med Mol Imaging. 2017;44(5):895–902.CrossRefPubMed
97.
Tripathi M, et al. HIV encephalitis with subcortical tau deposition: imaging pathology in vivo using F-18 THK 5117. Eur J Nucl Med Mol Imaging. 2016;43(13):2456–7.CrossRefPubMed
98.
Dani M, Brooks DJ, Edison P. Tau imaging in neurodegenerative diseases. Eur J Nucl Med Mol Imaging. 2016;43(6):1139–50.CrossRefPubMed
Metadaten
Titel
Differentiating HIV-Associated Neurocognitive Disorders From Alzheimer’s Disease: an Emerging Issue in Geriatric NeuroHIV
verfasst von
Benedetta Milanini
Victor Valcour
Publikationsdatum
05.08.2017
Verlag
Springer US
Erschienen in
Current HIV/AIDS Reports / Ausgabe 4/2017
Print ISSN: 1548-3568
Elektronische ISSN: 1548-3576
DOI
https://doi.org/10.1007/s11904-017-0361-0

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

19.04.2024 | Vorhofflimmern | Nachrichten

Parodontalbehandlung verbessert Prognose bei Katheterablation

18.04.2024 | Arterielle Hypertonie | Nachrichten

Antihypertensiva schützen auch alte Menschen noch vor Demenz

18.04.2024 | Wirbelsäulenmetastase | Nachrichten

Stereotaktische Radiatio schlägt konventionelle Bestrahlung

17.04.2024 | DGIM 2024 | Nachrichten

Denken Sie bei starker Blutung auch an die Hemmkörper-Hämophilie
weitere anzeigen

Update Innere Medizin

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

Newsletter bestellen
Bildnachweise