DOUBLE-BLIND PLACEBO-CONTROLLED STUDY OF METRIFONATE, AN ACETYLCHOLINESTERASE INHIBITOR, FOR ALZHEIMER-DISEASE

Fifty patients with probable Alzheimer disease (AD) completed a 3-mont h double-blind study to compare metrifonate to placebo. We dosed metri fonate to achieve a 40-60% inhibition of red blood cell acetylcholines terase activity. The Alzheimer Disease Assessment Scale cognitive subs cale score (ADAS-C) served as the primary outcome measure. At the comp letion of 3 months of treatment, the metrifonate group ADAS-C score di ffered significantly from the placebo group score by 2.6 points (g <0. 01). A 0.75-point trend toward improvement occurred during treatment i n the ADAS cognitive performance of the metrifonate group (p=0.15), an d a 1.10-point deterioration in cognitive performance was found in the placebo group (p <0.02). On the Global Improvement Scale (GIS), the t wo groups differed significantly on their changes from baseline to tre atment phase (p <0.02). Significant deterioration occurred in GIS scor es (p <0.01) and in Mini Mental State Examination (MMSE) scores (p <0. 03) in the placebo-treated group. Adverse effects were uncommon and di d not require adjustment of the dose of metrifonate or discontinuation of treatment. We achieved a mean of 52.3% decrease in red blood cell acetylcholinesterase activity. During up to 18 months of subsequent op en metrifonate treatment of patients, we found a deterioration of 1.68 points per year in MMSE performance. These findings support further s tudy of the effects of metrifonate on deterioration rate in AD.