Propentofylline in adult-onset cognitive disorders: double-blind, placebo-controlled, clinical, psychometric and brain mapping studies.

In a double-blind, placebo-controlled parallel group trial, the therapeutic efficacy and central effects of propentofylline (HWA 285) - a xanthine derivative with neuroprotective, metabolic, hemorheologic and antithrombotic action - were studied in 190 elderly outpatients with mild to moderate chronic cognitive disturbances (mild dementia, DSM-III-R). They received after a 2-week run-in period (placebo) for 12 weeks either 3 x 300 mg propentofylline or 3 x 1 tablet placebo (given at least 1 h before meals). The verum group (n = 96, age 68 +/- 9) was comparable to the placebo group (n = 94, age 69 +/- 8) in regard to age, height, smoking, consumption of stimulating alcoholic drinks, family and living status. Clinical evaluation by the Gottfries-Brane-Steen (GBS) scale demonstrated a significant superiority of propentofylline over placebo in the total score and the four GBS factors (motor, intellectual, emotional functions and other symptoms) as well as in the clinical global impression and Mini-Mental State. Psychometric measures showed slight and significant improvement in both groups but no intergroup differences. EEG brain mapping was carried out before and after 12 weeks' treatment in the Viennese subsample involving 24 propentofylline and 24 placebo patients. Propentofylline-treated patients exhibited, as compared with placebo-treated ones, a trend towards augmentation of total power, furthermore an increase in relative delta and beta and a decrease in alpha power, an acceleration of the dominant frequency as well as a slowing of the centroid of the combined delta/theta band. The total centroid tended towards acceleration, while the centroid deviation increased significantly. These alterations reflect vigilance changes of the dissociative type and differ from those of the classical nootropics. Clinical and psychometric evaluations demonstrated changes in the same direction as in the total sample, but interdrug differences were not significant. Thus, EEG brain mapping seems to be more sensitive in objectivating central drug effects.