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

Tiffany W Chow^1–6, Ariel Graff-Guerrero^4,6, Nicolaas PLG Verhoeff^2–4,7, Malcolm A Binns^3,8, David F Tang-Wai^5,9, Morris Freedman^1,3,5, Mario Masellis^5,10, Sandra E Black^3,5,10, Alan A Wilson^4,6, Sylvain Houle^4,6, Bruce G Pollock^4,6
1Division of Neurology, ²Department of Psychiatry, ³Rotman Research Institute, Baycrest; ⁴Departments of Psychiatry, ⁵Medicine, Division of Neurology, University of Toronto; ⁶Centre for Addiction and Mental Health PET Centre; ⁷Kunin-Lunenfeld Applied Research Unit, Baycrest; ⁸Dalla Lana School of Public Health, University of Toronto; ⁹University Health Network Memory Clinic; ¹⁰LC Campbell Cognitive Neurology Research Unit, Department of Medicine (Neurology), Sunnybrook Health Sciences Centre, Toronto, ON, Canada

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 [¹⁸F]-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, frontotemporal dementia, metabolism, PET scan, semantic dementia