FDG-PET in Semantic Dementia after 6 Months of Memantine: an Open-Label Pilot Study

To follow up on the increases we reported in normalized metabolic activity in salience network hubs from a 2-month open-label study of memantine in frontotemporal dementia (FTD).We repeated fluorodeoxyglucose positron emission tomography (FDG-PET) after 6 months of drug use and subjected the data to Statistical Parametrical Mapping (SPM) analysis to reveal clusters of significant change from baseline. We also sought correlations between changes in behavioral disturbances on the Frontal Behavioral Inventory (FBI) and the PET signal.Recruitment of one progressive nonfluent aphasia and one behavioral variant FTD precluded statistical analysis for any FTD subtype other than semantic dementia (SD). The baseline-to-6-month interval showed increased normalized metabolic activity in the left orbitofrontal cortex (p 0.002) for five participants with SD. The 2-6-month interval revealed a late increase in normalized metabolic activity in the left insula (p 0.013), right insula (p 0.009), and left anterior cingulate (p 0.005). The right anterior cingulate showed both an initial increase and a delayed further increase (2-6 months, p 0.016). FBI scores worsened by 43.3%. One participant with SD opted not to continue memantine beyond 2 months yet showed similar FDG-PET increases.Increases in normalized cortical metabolic activity in salience network hubs were sustained in SD over a 6-month period. Because one participant without medication also showed these changes, further investigation is recommended through a double-blind, placebo-controlled study with FDG-PET as an outcome measure.