Galantamine treatment in Alzheimer's disease: response and long-term outcome in a routine clinical setting

Åsa K Wallin, Carina Wattmo, Lennart Minthon
Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden

Background: In the absence of long-term, placebo-controlled studies of cholinesterase inhibitors in Alzheimer's disease (AD), analysis of the results of open-label trials becomes crucial. This study aimed to explore the three-year effects of galantamine treatment, as well as subgroups of response and adherence to treatment.
Methods: Two hundred and eighty patients with a clinical diagnosis of AD were included in the prospective, open-label, multicenter Swedish Alzheimer Treatment Study, and received galantamine treatment. Efficacy measures included cognitive tests, ie, the Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-cog), functional rating (Instrumental Activities of Daily Living Scale [IADL]), and global rating. Assessments were carried out before treatment and every six months for a period of three years. K-means cluster analysis was used to identify response subgroups.
Results: After three years of treatment, the mean change from baseline was 2.6 points in MMSE and 5.6 points in ADAS-cog scores. Globally, half of the patients improved or remained unchanged for two years. Cluster analysis identified two response clusters. Cluster 1 included patients with low ability in ADAS-cog and IADL scores at baseline. Even though the patients in cluster 1 were older and less educated, they responded better at six months compared with patients in cluster 2. Cluster 2 included patients with better ADAS-cog and IADL scores at baseline. Patients in cluster 2 had a higher frequency of the APOE ε4 allele, a slower pretreatment progression rate, and remained in the study longer than those in cluster 1. Three-year completers (n = 129, 46%) received higher doses of galantamine compared with dropouts.
Conclusion: AD patients who received long-term galantamine treatment were cognitively and globally stabilized. Subgroup response analysis identified a better short-term response in older patients with lower cognitive and functional abilities at baseline, a faster pretreatment progression rate, and a lower incidence of the APOE ε4 allele. The galantamine dose was higher in the population of completers.

Keywords: Alzheimer's disease, long-term treatment, routine setting, cholinesterase inhibitor, galantamine, k-means cluster analysis, completion rates