Effect of memantine on resting state default mode network activity in Alzheimer's disease

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

Research output: Contribution to journalArticlepeer-review


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

Original languageEnglish
Pages (from-to)205-217
Number of pages13
JournalDrugs and Aging
Issue number3
Publication statusPublished - 2011


  • Alzheimer's-disease, treatment
  • Memantine, therapeutic use

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Geriatrics and Gerontology


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