nach oben

Erschienen in:

01.03.2011 | Original Research Article

Effect of Memantine on Resting State Default Mode Network Activity in Alzheimer’s Disease

verfasst von: Mr Marco Lorenzi, Alberto Beltramello, Nicola B. Mercuri, Elisa Canu, Giada Zoccatelli, Francesca B. Pizzini, Franco Alessandrini, Maria Cotelli, Sandra Rosini, Daniela Costardi, Carlo Caltagirone, Giovanni B. Frisoni

Erschienen in: Drugs & Aging | Ausgabe 3/2011

Einloggen, um Zugang zu erhalten

Abstract

Background

Memantine is an approved symptomatic treatment for moderate to severe Alzheimer’s disease that reduces the excitotoxic effects of hyperactive glutamatergic transmission. However, the exact mechanism of the effect of memantine in Alzheimer’s disease patients is poorly understood. Importantly, the default mode network (DMN), which plays a key role in attention, is hypoactive in Alzheimer’s disease and is under glutamatergic control.

Objective

To assess the effect of memantine on the activity of the DMN in moderate to severe Alzheimer’s disease.

Methods

Functional magnetic resonance imaging (MRI) data from 15 patients with moderate to severe Alzheimer’s disease, seven treated with memantine (mean±SD age 77±8 years, mean±SD Mini-Mental State Examination [MMSE] score 16±5) and eight with placebo (mean±SD age 76±6 years, mean±SD MMSE score 13±1), were acquired at baseline (T0) and after 6 months of treatment (T6). Resting state components were extracted after spatial normalization in individual patients with independent component analysis. The consistency of the components was assessed using ICASSO and the DMN was recognized through spatial correlation with a pre-defined template. Voxel-based statistical analyses were performed to study the change in DMN activity from T0 to T6 in the two groups.

Results

At T0, the two groups showed similar DMN activity except in the precuneus and cuneus, where the patients who started treatment with memantine had slightly greater activity (p <0.05 corrected for familywise error [FWE]). The prospective comparison between T0 and T6 in the treated patients showed increased DMN activation mapping in the precuneus (p <0.05, FWE corrected), while the prospective comparison in the untreated patients did not show significant changes. The treatment×time interaction term was significant at p <0.05, FWE corrected.

Conclusions

The results suggest a positive effect of memantine treatment in patients with moderate to severe Alzheimer’s disease, resulting in an increased resting DMN activity in the precuneus region over 6 months. Future studies confirming the present findings are required to further demonstrate the beneficial effects of memantine on the DMN in Alzheimer’s disease.

Nur mit Berechtigung zugänglich

Areosa SA, Sherriff F. Memantine for dementia. Cochrane Database Syst Rev 2005; (3): CD003154

Lopez OL, Becker JT, Wahed AS, et al. Long-term effects of the concomitant use of memantine with cholinesterase inhibition in Alzheimer disease. J Neurol Neurosurg Psychiatry 2009; 80(6): 600–7PubMedCrossRef

Peskind ER, Potkin SG, Pomara N, et al. Memantine treatment in mild to moderate Alzheimer disease: a 24-week randomized, controlled trial. Am J Geriatr Psychiatry 2006; 14(8): 704–5PubMedCrossRef

Tariot PN, Farlow MR, Grossberg GT. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA 2004; 291(3): 317–24PubMedCrossRef

Bakchine S, Loft H. Memantine treatment in patients with mild to moderate Alzheimer’s disease: results of a randomised, double-blind, placebo-controlled 6-month study. J Alzheimers Dis 2008; 13(1): 97–107PubMed

Schmidt R, Ropele S, Pendl B, et al. Longitudinal multimodal imaging in mild to moderate Alzheimer disease: a pilot study with memantine. J Neurol Neurosurg Psychiatry 2008; 79(12): 1312–17PubMedCrossRef

Parsons CG, Stöffler A, Danysz W. Memantine: a NMDA receptor antagonist that improves memory by restoration of homeostasis in the glutamatergic system — too little activation is bad, too much is even worse. Neuropharmacology 2007; 53(6): 699–723PubMedCrossRef

Seeman P, Caruso C, Lasaga M. Memantine agonist action at dopamine D2High receptors. Synapse 2008; 62(2): 149–53PubMedCrossRef

Giustizieri M, Cucchiaroni ML, Guatteo E, et al. Memantine inhibits ATP-dependent K+ conductances in dopamine neurons of the rat substantia nigra pars compacta. J Pharmacol Exp Ther 2007; 322(2): 721–9PubMedCrossRef

10.

Hesse S, Ballaschke O, Barthel H, et al. Dopamine transporter imaging in adult patients with attention-deficit/hyperactivity disorder. Psychiatry Res 2009; 171(2): 120–8PubMedCrossRef

11.

Gilden DL, Marusich LR. Contraction of time in attention-deficit hyperactivity disorder. Neuropsychology 2009; 23(2): 265–9PubMedCrossRef

12.

Monastero R, Camarda C, Pipia C, et al. Visual hallucinations and agitation in Alzheimer’s disease due to memantine: report of three cases. J Neurol Neurosurg Psychiatry 2007; 78(5): 546PubMedCrossRef

13.

Fox MD, Raichle ME. Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci 2007; 8(9): 700–11PubMedCrossRef

14.

Fransson P. How default is the default mode of brain function? Further evidence from intrinsic BOLD signal fluctuations. Neuropsychologia 2006; 44(14): 2836–45PubMedCrossRef

15.

Gusnard DA, Akbudak E, Shulman GL, et al. Medial prefrontal cortex and self-referential mental activity: relation to a default mode of brain function. Proc Natl Acad Sci U S A 2001; 98: 4259–64PubMedCrossRef

16.

Broyd SJ, Demanuele C, Debener S, et al. Default-mode brain dysfunction in mental disorders: a systematic review. Neurosci Biobehav Rev 2009; 33(3): 279–96PubMedCrossRef

17.

Rombouts S, Barkhof F, Goekoop R, et al. Altered resting state networks in mild cognitive impairment and mild Alzheimer’s. Hum Brain Mapp 2005; 26: 231–9PubMedCrossRef

18.

Liu Y, Wang K, Yu C, et al. Regional homogeneity, functional connectivity and imaging markers of Alzheimer’s disease: a review of resting-state fMRI studies. Neuropsychologia 2008; 46(6): 1648–56PubMedCrossRef

19.

Greicius MD, Srivastava G, Reiss AL, et al. Default-mode network activity distinguishes Alzheimer’s disease from healthy aging: evidence from functional MRI. Proc Natl Acad Sci U S A 2004; 101: 4637–42PubMedCrossRef

20.

Buckner RL, Snyder AZ, Shannon BJ, et al. Molecular, structural, and functional characterization of Alzheimer’s disease: evidence for a relationship between default activity, amyloid, and memory. J Neurosci 2005; 25: 7709–17PubMedCrossRef

21.

Moher D, Schulz KF, Altman DG. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomised trials. Lancet 2001; 357(9263): 1191–4PubMedCrossRef

22.

Altman DG, Schulz KF, Moher D, et al. The revised CONSORT statement for reporting randomized trials: explanation and elaboration. Ann Intern Med 2001; 134(8): 663–94PubMed

23.

McKhann G, Drachman D, Folstein M, et al. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984; 34(7): 939–44PubMedCrossRef

24.

Morris JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology 1993; 43: 2412–4PubMedCrossRef

25.

Rosen WG, Terry RD, Fuld PA, et al. Pathological verification of ischemic score in differentiation of dementias. Ann Neurol 1980; 7(5): 486–8PubMedCrossRef

26.

Protocollo MEM_T V0 [in Italian]. Brescia: Laboratorio di Epidemiologia e Neuroimaging, IRCCS [online]. Available from URL: http://www.centroalzheimer.it/Public/Protocollo_MEM_T0.doc [Accessed 2010 Nov 26]

27.

Lezak MD, Howieson DB, Loring DW, et al. Neuropsychological assessment. 4th ed. New York (NY): Oxford University Press, 2004

28.

Folstein MF, Folstein SE, McHugh PR. ‘Mini-mental state’: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12(3): 189–98PubMedCrossRef

29.

Cummings JL, Mega M, Gray K, et al. The neuropsychiatric inventory: comprehensive assessment of psychopathology in dementia. Neurology 1994; 44(12): 2308–14PubMedCrossRef

30.

Eshed I, Althoff CE, Hamm B, et al. Claustrophobia and premature termination of magnetic resonance imaging examinations. J Magn Reson Imaging 2007; 26(2): 401–4PubMedCrossRef

31.

Calhoun VD, Adali T, Pearlson GD, et al. A method for making group inferences from functional MRI data using independent component analysis. Hum Brain Mapp 2001; 14(3): 140–51PubMedCrossRef

32.

Correa N, Adali T, Calhoun VD. Performance of blind source separation algorithms for fMRI analysis using a group ICA method. Magn Reson Imaging 2007; 25(5): 684–94PubMedCrossRef

33.

Maldjian JA, Laurienti PJ, Kraft RA, et al. An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. Neuroimage 2003; 19(3): 1233–9PubMedCrossRef

34.

Hoyer S. Age as risk factor for sporadic dementia of the Alzheimer type? Ann N Y Acad Sci 1994 May 31; 719: 248–56PubMedCrossRef

35.

Noda M, Nakanishi H, Akaike N. Glutamate release from microglia via glutamate transporter is enhanced by amyloid-beta peptide. Neuroscience 1999; 92(4): 1465–74PubMedCrossRef

36.

Harris NG, Plant HD, Inglis BA, et al. Neurochemical changes in the cerebral cortex of treated and untreated hydrocephalic rat pups quantified with in vitro 1H-NMR spectroscopy. J Neurochem 1997; 68(1): 305–12PubMedCrossRef

37.

Magistretti PJ, Pellerin L. Astrocytes couple synaptic activity to glucose utilization in the brain. News Physiol Sci 1999 Oct; 14: 177–82PubMed

38.

Wu J, Anwyl R, Rowan MJ. beta-Amyloid selectively augments NMDA receptor-mediated synaptic transmission in rat hippocampus. Neuroreport 1995; 6(17): 2409–13PubMedCrossRef

39.

Johnson JW, Kotermanski SE. Mechanism of action of memantine. Curr Opin Pharmacol 2006; 6(1): 61–7PubMedCrossRef

40.

Gruetter R, Seaquist ER, Kim S, et al. Localized in vivo 13C-NMR of glutamate metabolism in the human brain: initial results at 4 tesla. Dev Neurosci 1998; 20(4–5): 380–8PubMedCrossRef

41.

Shen J, Petersen KF, Behar KL, et al. Determination of the rate of the glutamate/glutamine cycle in the human brain by in vivo 13C NMR. Proc Natl Acad Sci U S A 1999; 96(14): 8235–40PubMedCrossRef

42.

Sibson NR, Dhankhar A, Mason GF, et al. Stoichiometric coupling of brain glucose metabolism and glutamatergic neuronal activity. Proc Natl Acad Sci U S A 1998; 95(1): 316–21PubMedCrossRef

43.

Aubert A, Pellerin L, Magistretti PJ, et al. A coherent neurobiological framework for functional neuroimaging provided by a model integrating compartmentalized energy metabolism. Proc Natl Acad Sci USA 2007; 104(10): 4188–93PubMedCrossRef

44.

Magistretti PJ, Pellerin L. Cellular mechanisms of brain energy metabolism and their relevance to functional brain imaging. Philos Trans R Soc Lond B Biol Sci 1999; 354(1387): 1155–63PubMedCrossRef

45.

Lin AP, Shic F, Enriquez C, et al. Reduced glutamate neurotransmission in patients with Alzheimer’s disease: an in vivo (13) C magnetic resonance spectroscopy study. MAGMA 2003; 16(1): 29–42PubMedCrossRef

46.

Parpura-Gill A, Beitz D, Uemura E. The inhibitory effects of beta amyloid on glutamate and glucose uptakes by cultured astrocytes. Brain Res 1997; 754: 65–71PubMedCrossRef

47.

Minoshima S, Giordani B, Berent S, et al. Metabolic reduction in the posterior cingulate cortex in very early Alzheimer’s disease. Ann Neurol 1997; 42: 85–94PubMedCrossRef

48.

Damoiseaux JS, Keller KE, Menon V, et al. Default mode network connectivity tracks clinical progression in Alzheimer’s disease. San Francisco (CA): Organization for the Human Brain Mapping, 2009

49.

Peters M, Romieu P, Maurice T, et al. Involvement of the sigma 1 receptor in the modulation of dopaminergic transmission by amantadine. Eur J Neurosci 2004; 19(8): 2212–20CrossRef

50.

Meisner F, Scheller C, Kneitz S, et al. Memantine upregulates BDNF and prevents dopamine deficits in SIV-infected macaques: a novel pharmacological action of memantine. Neuropsychopharmacology 2008; 33(9): 2228–36PubMedCrossRef

51.

Achard S, Bullmore E. Efficiency and cost of economical brain functional networks. PLoS Comput Biol 2007; 3(2): e17PubMedCrossRef

52.

Thomas TC, Grandy DK, Gerhardt GA, et al. Decreased dopamine D4 receptor expression increases extracellular glutamate and alters its regulation in mouse striatum. Neuropsychopharmacology 2009; 34(2): 436–45PubMedCrossRef

53.

Konradi C, Leveque JC, Hyman SE. Amphetamine and dopamine-induced immediate early gene expression in striatal neurons depends on postsynaptic NMDA receptors and calcium. J Neurosci 1996; 16(13): 4231–9PubMed

54.

Keefe KA, Ganguly A. Effects of NMDA receptor antagonists on D1 dopamine receptor-mediated changes in striatal immediate early gene expression: evidence for involvement of pharmacologically distinct NMDA receptors? Dev Neurosci 1998; 20(2–3): 216–8PubMedCrossRef

55.

Northoff G, Walter M, Schulte RF, et al. GABA concentrations in the human anterior cingulate cortex predict negative BOLD responses in fMRI. Nat Neurosci 2007; 10(12): 1515–7PubMedCrossRef

56.

Molinaro G, Battaglia G, Riozzi B, et al. Memantine treatment reduces the expression of the K(+)/CL(−)cotrans-porter KCC2 in the hippocampus and cerebral cortex, and attenuates behavioural responses mediated by GABA(A) receptor activation in mice. Brain Res 2009; 1265: 75–9PubMedCrossRef

57.

Song MS, Rauw G, Baker GB, et al. Memantine protects rat cortical cultured neurons against beta-amyloid-induced toxicity by attenuating tau phosphorylation. Eur J Neurosci 2008; 28(10): 1989–2002PubMedCrossRef

58.

Frisoni GB, Fox NC, Jack CR, et al. The clinical use of structural MRI in Alzheimer disease. Nat Rev Neurol 2010 Feb; 6(2): 67–77PubMedCrossRef

59.

Lin Q, Zheng Y, Yin F, et al. A fast algorithm for one-unit ICA-R. Information Sci 2007; 177: 1265–75CrossRef

Titel: Effect of Memantine on Resting State Default Mode Network Activity in Alzheimer’s Disease
verfasst von: Mr Marco Lorenzi
Alberto Beltramello
Nicola B. Mercuri
Elisa Canu
Giada Zoccatelli
Francesca B. Pizzini
Franco Alessandrini
Maria Cotelli
Sandra Rosini
Daniela Costardi
Carlo Caltagirone
Giovanni B. Frisoni
Publikationsdatum: 01.03.2011
Verlag: Springer International Publishing
Erschienen in: Drugs & Aging / Ausgabe 3/2011
Print ISSN: 1170-229X
Elektronische ISSN: 1179-1969
DOI: https://doi.org/10.2165/11586440-000000000-00000

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

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

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

Newsletter bestellen

Springer Medizin

Abstract

Background

Objective

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2011

Effects of Anticholinergic Drugs on Verbal Episodic Memory Function in the Elderly

Naproxen/Esomeprazole Fixed-Dose Combination

Use of Low-Molecular-Weight Heparins and New Anticoagulants in Elderly Patients with Renal Impairment

Optimal Pharmacotherapeutic Management of Chronic Lymphocytic Leukaemia

Polypharmacy, Aging and Potential Drug-Drug Interactions in Outpatients in Taiwan