Open-label study of the short-term effects of memantine on FDG-PET in frontotemporal dementia

Tiffany W Chow, Ariel Graff-Guerrero, Nicolaas Plg Verhoeff, Malcolm A Binns, David F Tang-Wai, Morris Freedman, Mario Masellis, Sandra E Black, Alan A Wilson, Sylvain Houle, Bruce G Pollock, Tiffany W Chow, Ariel Graff-Guerrero, Nicolaas Plg Verhoeff, Malcolm A Binns, David F Tang-Wai, Morris Freedman, Mario Masellis, Sandra E Black, Alan A Wilson, Sylvain Houle, Bruce G Pollock

Abstract

Background: Memantine has shown effects on cortical metabolism in Alzheimer's disease (AD), and the mechanism of action may not be specific to AD alone. We hypothesized that participants with frontotemporal dementia taking memantine would show an increased cortical metabolic activity in frontal regions, temporal regions, or in salience network hubs.

Methods: Sixteen participants with behavioral or language variant frontotemporal dementia syndromes (FTD) were recruited from tertiary FTD clinics and treated with memantine hydrochloride 10 mg twice daily in this fixed-dose, open-label pilot study. The primary endpoint was enhancement of cortical metabolic activity after 7-8 weeks of treatment. Secondary endpoints were measures of mood and behavior disturbance, frontal executive function, and motor disturbance.

Results: Voxel-wise parametric image analysis of positron emission tomography (PET) data from seven behavioral variant FTD patients, eight semantic dementia patients, and one progressive nonfluent aphasia patient, of mean age 64.3 years, mean duration of illness 4.25 years, and baseline mean sum of boxes Clinical Dementia Rating score 6.59, revealed an increase in [(18)F]-fluorodeoxyglucose (FDG) normalized metabolic activity in bilateral insulae and the left orbitofrontal cortex (P < 0.01). The increase on FDG-PET did not correlate with changes on behavioral inventories. Post hoc analysis indicated that semantic dementia participants drove this finding.

Conclusion: This open-label clinical PET study suggests that memantine induces an increase in metabolism in the salience network in FTD. A placebo-controlled follow-up study is warranted.

Keywords: Alzheimer’s disease; PET scan; frontotemporal dementia; metabolism; semantic dementia.

Figures

Figure 1
Figure 1
Flowchart for recruitment, including early withdrawals.
Figure 2
Figure 2
Clusters of at least 10 voxels in bilateral insulae and left orbitofrontal cortex where the t-contrast for increase between baseline and 2-month FDG-PET normalized metabolic activity had P values <0.01. Color bars indicate t statistic values. Volumes of interest are shown on the T1-weighted template created from the average of all 16 participants with frontotemporal atrophy in the MNI space. Abbreviation: MNI, Montreal Neurological Institute.

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