Potential long-term effects of rivastigmine on disease progression may be linked to drug effects on vascular changes in Alzheimer brains

Alzheimer's disease patients with hypertension or other vascular risk factors have been shown to receive greater symptomatic benefits than patients with strictly Alzheimer's disease following short-term treatment with rivastigmine, an inhibitor of acetylcholinesterase and butyrylcholinesterase. We evaluated the long-term efficacy of rivastigmine in Alzheimer's disease patients with or without hypertension. Subjects in a 26-week placebo-controlled trial of rivastigmine entered an open-label extension study for 104 weeks. Efficacy measures included the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Progressive Deterioration Scale (PDS) and Global Deterioration Scale (GDS). Subjects were stratified by the presence or absence of hypertension at baseline. At 104 weeks, there was a trend for hypertensive patients from the original rivastigmine 6-12 mg/day group (early starters), who received rivastigmine for the full 104 weeks) to have better ADAS-cog scores than the original placebo group (late starters), who received open-label rivastigmine for the last 78 weeks only). Significant treatment differences were observed in the hypertensive subgroup on the PDS and GDS. In non-hypertensive patients, changes from baseline at week 104 were similar in 'early' and 'late' starters of rivastigmine treatment. The additional apparent benefits on disease progression detected in patients with hypertension and Alzheimer's disease may be linked to drug effects on cerebrovascular factors. These findings may have an important influence on the way cholinesterase inhibitors are prescribed.