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.
Effect of memantine on resting state default mode network activity in Alzheimer's disease.
BELTRAMELLO, ALBERTO;ZOCCATELLI, Giada;PIZZINI, Francesca;ALESSANDRINI, FRANCO;
2011-01-01
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.
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