Acute treatment with the PDE4 inhibitor roflumilast improves verbal word memory in healthy old individuals : a double-blind placebo-controlled study

Abstract There is ample evidence that PDE4 inhibition can improve memory performance in animal studies. In the current study, we examined the acute effects of the PDE4 inhibitor roflumilast on memory performance in healthy subjects (60-80 years of age). We tested the effects of acute roflumilast administration (100, 250, 1000 μg) in a double-blind, placebo-controlled, 4-way crossover design. Participants were first screened for their verbal word memory performance to ensure normal memory performance (within 0.5 STDEV from norm score; n=20) Drug effects on memory performance were tested in a verbal memory test and a spatial memory test. Reported side effects of drug treatment were registered. Roflumilast (100 μg) improved the delayed-recall performance of the participants (Cohen’s d, 0.69). No effects were observed in the spatial memory task. Roflumilast was well tolerated at this low dose. Although no clear adverse side effects were reported at the low dose, mild adverse events (including headache, dizziness, insomnia and diarrhoea) were reported after the 1000 μg dose. The current study provides first evidence that the PDE4 inhibitor roflumilast improves verbal memory performance in old participants. The current data encourage further development of PDE4 inhibitors for improving memory.