Typically, patients may be expected to survive for up to a decade after the diagnosis of AD. The combination of the need for early treatment and the long natural history of AD means that treatment may continue for many years. It is therefore essential that agents used in treating AD be safe and effective with long-term use. Although the safety and efficacy of AChEIs have been proven for up to 1 year, they have yet to be clearly established for long-term use. Most long-term trials rely on an historical placebo-treated cohort or a calculated predicted rate of decline based on the rate of decline in the double-blind phase of the trial (Beier MT).

Data from a further extension study (Raskind MA etal) on galantamine safety and efficacy for up to 3 years of continuous use have recently been published. All patients had completed open-label extensions to one of two earlier double-blind studies, and had received galantamine 24 mg per day during earlier open-label extensions, thus having had at least 6 months of treatment prior to this study. During this extension study, patients received open-label galantamine 24 mg per day for an additional 24 months.

Cognitive decline in galantamine-treated subjects was compared with that in a clinically similar historical control sample of AD patients who had received placebo for 12 months and with the mathematically predicted decline of untreated patients over 36 months. Patients treated continuously with galantamine for 36 months increased a mean +/- SE of 10.2 +/- 0.9 points on the Alzheimer's Disease Assessment Scale-11-item cognitive subscale-a substantially smaller cognitive decline (approximately 50%) than that predicted for untreated patients. Patients discontinuing galantamine therapy before 36 months had declined at a similar rate before discontinuation as those completing 36 months of treatment. Almost 80% of patients who received galantamine continuously for up to 36 months seemed to demonstrate cognitive benefits compared with those predicted for untreated patients. Thus, the authors concluded that the cognitive decline over 36 months of continuous galantamine treatment was substantially less than the predicted cognitive decline of untreated patients with mild to moderate dementia. These findings suggest that galantamine slows the clinical progression of AD.