Nicergoline in the Treatment of Mild-to-Moderate Alzheimer??s Disease

Abstract

To assess the long-term efficacy and tolerability of nicergoline 30mg twice daily in the treatment of mild-to-moderate Alzheimer's disease. Multicentre, randomised, double-blind, placebo-controlled study of 6 months' duration. 33 investigational sites in five European countries (Italy, Sweden, UK, Belgium and Germany). 346 patients with mild-to-moderate probable Alzheimer's disease (as defined by the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association), with Mini-Mental State Examination scores of 12 to 24, aged >50 years. Patients were randomised to either nicergoline 30mg tablets twice daily or to matching placebo treatment for 6 months. Primary efficacy measures were the cognitive portion of the Alzheimer's Disease Assessment Scale (ADAS-cog) and the Clinical Global Impression of Change (CGIC); the ADAS non-cognitive portion (ADAS non-cog) and total score, the Instrumental Activities of Daily Living (IADL), and the Physical Self-Maintenance Scale (PSMS) were considered as secondary measures. The completion rate was 83.6% for nicergoline and 81.1% for the placebo group. The two groups were well balanced for all demographic and disease characteristics, except education, which was higher in the placebo group. Cognitive function (ADAS-cog) at endpoint was significantly improved by nicergoline (mean change from baseline was −0.17 in the nicergoline group and 1.38 in the placebo group, p = 0.04). The CGIC rating revealed a non-significantly reduced rate of deterioration in the nicergoline group; the same applied to IADL and PSMS results. ADAS non-cog non-significantly favoured the nicergoline group and fewer nicergoline patients developed newly emergent non-cognitive symptoms during the study. The ADAS total score closely reflected ADAS-cog changes. 59.9% of nicergoline and 60.9% of placebo recipients reported adverse events, usually of mild severity and self-limiting; adverse events determined discontinuation in 8.5% of nicergoline and 8.3% of placebo patients. The metabolic system was most frequently affected in nicergoline patients due to the high incidence of hyperuricaemia; psychiatric adverse events were more frequently represented in the placebo group. Serious adverse events occurred in 22 patients per treatment group. Nicergoline was well tolerated and exerted a positive effect on the cognitive symptoms of mild-to-moderate Alzheimer's disease, indicating a therapeutic potential that needs to be confirmed with further investigations.