Amantadine infusions in mild dementia: acute double-blind placebo-controlled EEG mapping and psychometric studies

In a double-blind, placebo-controlled study, the acute central effects of amantadine infusions (200 mg for 1 h) were studied in 20 mildly demented patients (DSM-III-R) utilizing EEG mapping as well as psychometry and psychophysiology at the hours 0, 2, 4, 6 and 8. Multivariate analysis of the EEG demonstrated a significant CNS effect of 200 mg amantadine as compared with placebo mostly at the 4th and 6th hour. These effects were primarily over temporo-occipital, fronto-temporal and temporal regions. Univariate analysis showed a decrease of total power and of absolute power in all frequency bands. Furthermore, an increase of relative delta and beta activities, a decrease of theta and alpha activities, as well as an acceleration of the respective centroids of the alpha, beta and total activity were observed. The delta/theta centroid showed initially a slight increase and thereafter a clear decrease. The changes were similar to those seen after psychostimulants. Multivariate analysis of noopsychic variables showed an improvement in the 6th hour after amantadine and no changes after placebo, but inter-drug differences did not reach significance. Univariate analyses revealed differential results which included improvement in digit span and deterioration in the speed related test such as DSST and reaction time. In thymopsychic variables, de-activation was observed after amantadine as compared with placebo in the 2nd to the 6th hour with a maximum in the 4th hour. As patients felt themselves slightly over-activated before treatment, de-activation may be regarded as improvement of vigilance in the narrow sense of the word. There were no psychophysiological changes.