Dihydroergokryptine vs. placebo in dementia of Alzheimer type: interim results of a randomized multicenter study after a 1-year follow-up.

In order to evaluate the efficacy of dihydroergokryptine mesylate (DEK) - a semisynthetic ergot alkaloid having a neuroprotective activity through the activation of antioxidant enzymatic systems - in dementia of Alzheimer type, a long-term, randomized, placebo-controlled, double-blind study was carried out. The interim analysis after 1-year follow-up is here reported. Two-hundred-and-fifteen patients fulfilling the NINCDS-ADRDA criteria for probable Alzheimer's disease were enrolled by 14 geriatric and neurologic Italian centers. The study design included a 1-month pre-treatment phase with placebo; 1-year double-blind treatment with DEK or placebo; a further 1-year open phase of treatment with DEK. The active drug dosage was 5 mg bid orally administered for the first 2 weeks, 10 mg bid for the following 2 weeks, 20 mg bid for the following 11 months. Efficacy was assessed by means of Gottfries-Bråne-Steen (GBS) Rating Scale for dementia and Mental Deterioration Battery. The univariate analysis showed a significant improvement of GBS subscales and factors (with the exception of the Factor III, depression-anxiety). Multivariate analysis showed a significant difference between treatments in GBS scale (P=0.002) without any influence of age and illness duration. These results were confirmed by the end-point analysis carried out on GBS scores using baseline value as covariate. Minor adverse events were observed in 9 out of 108 patients (8.3\%) of the DEK group and in 7 out of 107 (6.5\%) of the placebo group. No change in blood pressure, heart rate and routine laboratory tests was observed. These preliminary results suggest positive symptomatic effects of DEK on elderly patients with probable Alzheimer's disease indicating a slowing down of the cognitive decline.