Premium
O3‐05‐08: The effect of memantine on FDG‐PET imaging in frontotemporal dementia
Author(s) -
Chow Tiffany W.C.,
Graff-Guerrero Ariel,
Freedman Morris,
Tang-Wai David,
Black Sandra E.,
Pollock Bruce
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2010.05.426
Subject(s) - memantine , frontotemporal dementia , psychology , medicine , dementia , positron emission tomography , semantic dementia , neuroscience , oncology , disease
Background: Patients with FTD have no FDA-approved disease-modification intervention. Memantine’s purported mechanism of action is NMDAreceptor antagonism and resultant changes to cortical excitation. It is therefore potentially useful for neurodegenerative dementias other than Alzheimer’s disease, but at this time its use for FTD is an unlabeled indication. Methods: 11 subjects with behavioral or language variant FTD titrated up to a dose of memantine 10mg bid. FDG-PET scans were performed at baseline and 7-8 weeks after starting drug, which was targeted as the time to attain a steady state plasma level. The Frontal Behavioural Inventory, Stereotypy Rating Inventory, motor component of the United Parkinson’s Disease Rating Scale, and the Clinical Dementia Rating Scale modified for FTD were secondary outcome measures. Results: 8 of the 11 caregivers involved in monitoring benefit from the memantine have requested continuation of memantine by prescription after the study, based on their observations that patients were behaviourally or cognitively improved with the drug. Baseline PET images revealed expected frontotemporal hypometabolic defects for each of the subjects. SPM group analysis of the PET data revealed 3 voxel clusters of significant increased uptake: left parahippocampal gyrus, left caudate, and right anterior cingulate with p values < .05. In addition, there is a voxel cluster of significantly decreased uptake in the L cerebellum. Figure shows the right anterior cingulate voxel cluster on a T1-weighted image averaged from the subjects and fit to MNI space. The changes on FDGPET do not correlate with changes in secondary outcome measure scores. No serious adverse events have occurred to-date. Conclusions: Preliminary results for this open-label trial with target recruitment N 1⁄4 15 raise questions about whether memantine has a neuroprotective effect on FTD that is as yet not evident in clinical behavioral inventory changes. PET data at 6 months may provide further evidence to support or refute this effect, but this preliminary data suggests a placebo-controlled RCT may be warranted.