Propentofylline (HWA 285, Hoechst AG) is a novel xanthine derivative that increases the level of the second messenger cyclic adenosine monophosphate and the release of nerve growth factor that is a selective neurotrophic factor for cholinergic neurons. These pharmacological properties and also the results of phase II studies support the hypothesis that patients with AD would benefit from treatment with propentofylline.Thus, we studied 25 patients with the clinical diagnosis of probable AD according to NINCDS-ADRDA criteria in a double blind, placebo-controlled trial. All patients were mildly to moderately demented and scored between 15 and 25 on the mini-mental-state test (MMSE). Before and after a 12 week treatment period patients underwent neuropsychological testing as well as measurement of regional cerebral glucose metabolism (rCMRGl) using PET of 1 8 F-2-fluoro-2-deoxy-D-glucose (FDG) at resting and stimulation by a verbal memory task.Before treatment the groups were comparable to severity of dementia and rCMRGl at resting and under cognitive stimulation. After 3 months treatment with propentofylline we observed a significant increase of the global stimulation effect in contrast to a decrease in the placebo group (p<0.01). Regional changes of stimulation effects were mostly reflected in the basal ganglia (p<0.001), thalamus (p<0.01), sensorimotor cortex (p<0.01), temporoparietal (p<0.05) and frontal association cortex (p<0.05).In conclusion, the present study demonstrated in AD positive effects of propentofylline on cerebral metabolic response to memory tasks. To proof the longterm clinical efficacy further multicenter trials are necessary.