Efficacy of rivastigmine in subjects with moderately severe Alzheimer's disease

Cholinesterase (ChE) inhibitors are primarily used in the treatment of mild to moderate Alzheimer's disease (AD), but may also be effective in more severe disease.

To evaluate the dual ChE inhibitor, rivastigmine, in more severe dementia.

We retrospectively analysed pooled data from three randomised, placebo-controlled, double-blind, 6-month trials, involving 2126 AD subjects. Subjects were selected according to baseline Mini-Mental State Examination (MMSE) score to identify subjects with more severe cognitive impairment (10-12 MMSE points). One-hundred-and-seventeen subjects were included who had been treated with rivastigmine 6-12 mg/day or placebo. The AD Assessment Scale-Cognitive Subscale (ADAS-Cog), the MMSE, a six-item subscore of the Progressive Deterioration Scale (PDS) and the BEHAVE-AD assessed efficacy. Tolerability was assessed by recording adverse events (AEs) and the relative risk (RR) of discontinuation.

This group of subjects responded well to rivastigmine. After 6 months, the mean ADAS-Cog score declined by 6.3 points in the placebo group and increased by 0.2 points in the rivastigmine group (observed cases; p<0.001). Clinical benefits were also observed with the MMSE, the six-item PDS score and items of the BEHAVE-AD. Rivastigmine showed the same pattern of AEs as in other studies, but the RR of dropping out due to AEs was lower than in subjects with milder AD.

Current treatment guidelines do not recommend treating individuals with severe AD with ChE inhibitors. However, this retrospective analysis suggests that rivastigmine 6-12 mg/day may benefit subjects with more severe disease, as well as subjects with mild to moderate impairment.