title: Open-label study of the short-term effects of memantine on FDG-PET in frontotemporal dementia.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Neurology, Baycrest.
authors.forename: Tiffany W
authors.initials: TW
authors.lastname: Chow
authors.forename: Ariel
authors.initials: A
authors.lastname: Graff-Guerrero
authors.forename: Nicolaas Plg
authors.initials: NP
authors.lastname: Verhoeff
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: Binns
authors.forename: David F
authors.initials: DF
authors.lastname: Tang-Wai
authors.forename: Morris
authors.initials: M
authors.lastname: Freedman
authors.forename: Mario
authors.initials: M
authors.lastname: Masellis
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Black
authors.forename: Alan A
authors.initials: AA
authors.lastname: Wilson
authors.forename: Sylvain
authors.initials: S
authors.lastname: Houle
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Pollock