Many patients with FTD are treated off-label with AD medications (cholinesterase inhibitors and memantine), despite the lack of evidence of efficacy . Since there is a relative preservation of cholinergic neurons in FTD, the absence of benefit of cholinesterase inhibitors in patients with FTD comes as no surprise [84, 102]. Cholinesterase inhibitors may even worsen behavioral symptoms, especially disin- hibition and compulsiveness .
After some small open-label studies and a first negative multicenter randomized placebo-controlled trial of 49 patients  , a multicenter randomized doubleblind, placebo-controlled trial has been conducted in 81 patients with FTD or semantic dementia with 20-mg memantine daily during 26 weeks . There was no significant effect of memantine on the NPI or on the Clinical Global Impression of Change (CGIC) Scale. Furthermore, patients under memantine had more cognitive adverse events than patients under placebo.