Five-Year Effects of Rivastigmine on Cognitive Performance

Author: Mary Sano, MD, Professor of Medicine, Mount Sinai School of Medicine, New York, New York

Alzheimer’s disease (AD) is characterized by a relentless decline in cognitive performance and in the ability to perform normal daily tasks. Untreated or placebo-treated patients with AD show an average annual deterioration of about three points on the Mini-Mental State Examination (MMSE) or, depending on baseline levels, five to seven points on the Cognitive sub-scale of the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog). Short-term symptomatic treatments, such as cholinesterase inhibitors, are available for mild-to-moderate AD, but achieving further delay in cognitive decline or slowing long-term deterioration of symptoms would be clinically meaningful.

An earlier five-year study of rivastigmine (Exelon®, Novar-tis) suggested slowed deterioration when MMSE scores were compared with modeled projections. The ADAS-Cog, however, provides a more extensive and sensitive assessment of cognitive function than the MMSE. In addition, the Global Deterioration Scale (GDS) can be used to evaluate the clinical meaningfulness of ADAS-Cog.
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Investigators pooled data from large, open-label extension studies of ADAS-Cog scores in 1,998 patients. In those studies, patients completing placebo-controlled rivastigmine trials had been invited to continue open-label rivastigmine (up to 12 mg) for up to five years. Mean ADAS-Cog scores and mean changes from baseline were calculated and compared with validated projections for untreated decline. They assessed the length of time that patients’ scores remained above predetermined ADAS-Cog levels.

During the evaluation period, 22.4% of the patients had withdrawn from the study because ofADEs, and 16% withdrew their consent for other reasons. The baseline characteristics of the remaining patients were similar to those of the entire group, but their cognitive impairment was milder: a mean ADAS-Cog score of 17.4 vs. 24.6 for the overall population and a mean GDS score of 3.7 vs. 4.1 for the overall population.

The ADAS-Cog score threshold of 23 corresponded to moderate dementia (a GDS score of 4); a threshold of 33, moderately severe dementia (a GDS score of 5), and a threshold of 45, severe dementia (a GDS score of 6). For model-based untreated patients, mean ADAS-Cog scores increased beyond the threshold for moderately severe dementia (ADAS-Cog = 33) at approximately 1.5 years. canadian pharmacy viagra

For patients receiving rivastigmine, the ADAS-Cog scores exceeded 33 after 2.5 years of treatment. Subsequently, mean ADAS-Cog scores increased past the severe AD threshold of 45 at approximately three years for the model-based untreated patients, compared with the rivastigmine-treated patients, who had not passed that threshold at five years (36.8 for the 75 patients remaining in the study).

The projected ADAS-Cog score for untreated patients was 56.9 at five years. The observed mean increase from baseline at five years in ADAS-Cog for the rivastigmine-treated patients was 19.4 points; for the untreated model-based patients, it was 27.3 points.

The most common side effects were gastrointestinal, and these tended to subside in a few weeks after the patients were stabilized on an acceptable dose. online pharmacy prescription drugs

In general, these results suggest that rivastigmine, which is a sustained dual inhibitor of acetylcholinesterase and butyryl-cholinesterase, might have long-term clinical efficacy in AD patients. It appeared to slow the decline of cognitive symptoms of patients remaining in the study by up to 40% for as long as five years. It stabilized patients, thus delaying deterioration by up to two years. In terms of reducing the burden for care-givers, it is possible that the patients who are taking rivastig-mine might remain interactive longer, need less supervision, and stay more alert.