Nimodipine in the Treatment of Probable Alzheimer's Disease: Results of Two Multicentre Trials

The results of both in vitro and animal studies suggest that calcium dysregulation plays an important role in neuronal cell degeneration, and thus support the use of calcium antagonists for the treatment of Alzheimer's disease (AD). The aim of this pooled analysis of 2 multicentre randomised trials was to assess the efficacy and tolerability of nimodipine administered for 6 months in a total of 1648 patients with probable AD. There were no statistically significant differences between nimodipine and placebo for any of the primary outcome variables. However, significant improvements in the secondary variable, Mini Mental State Examination (MMSE; p = 0.004) score, compared with the placebo group, were noted when the individual study data were pooled. Differences favouring nimodipine also emerged when patients were stratified according to their baseline MMSE scores. In more severely impaired patients (MMSE scores 12 to 18), nimodipine 180 mg/day was significantly superior to placebo for Alzheimer's Disease Assessment Scale (ADAS) total (p = 0.01) and cognitive (p = 0.035) scores as well as MMSE total score (p = 0.006). Secondary analyses of these data indicated that patients with more severe cognitive disturbances, yet able to recall ≥ 1 word twice in succession (BSR test), demonstrated the greatest response to nimodipine 180 mg/day treatment. Nimodipine was well tolerated when administered at either 90 or 180 mg/day. In conclusion, although nimodipine did not significantly slow disease progression in the overall study population, patients with moderately severe dementia did appear to benefit from nimodipine treatment, especially those who performed well on the selective reminding test.