Effect of galantamine on verbal repetition in AD: a secondary analysis of the VISTA trial
Rockwood K, Fay S, Jarrett P, Asp E;
Commented by , 30 Apr 2007
Aim of the study
To assess the importance of verbal repetition as a target symptom in AD using the cholinesterase inhibitor galantamine.
Method
Secondary analysis of the Video-Imaging Synthesis of Treating Alzheimer's disease (VISTA) study, which compared galantamine to placebo over 4 months in 130 persons with mild to moderate AD, defined as MMSE score between 10 and 25 and an ADAS-cog score of 18 or higher. The primary outcome was Goal Attainment Scaling (GAS) in which individualized problems identified at baseline by patients, caregivers and physicians are assessed bimonthly by two independent raters. Other outcomes included the CIBIC-plus, ADAS-cog, DAD, CBS.
Results
Reduction of verbal repetition (particularly repetitive questioning and story telling) was set as a treatment goal in 44% of randomized subjects. More patients and caregivers (32%) set repetition goals than physicians (18%). After 4 months more galantamine than placebo-treated patients showed a reduction of verbal repetition (58% vs 24%; p < 0.01). This reduction correlated with improvement in other clinical measures such as the patient-rated GAS and the CIBIC-plus, but not the ADAS-cog.
Professor Gauthier's comments
The authors conclude that a reduction of verbal repetition is a clinical marker of a positive clinical response to a cholinesterase inhibitor. It can be used to begin discussion about treatment benefits with such drugs in mild to moderate AD.
The original report of the VISTA Study can be found in the CMAJ 2006; 174 (8); 1099-1105 (ref. 1). The great novelty of that study was using individualized treatment goals as primary outcome. The clinicians observed a significantly greater improvement of the GAS as a whole (3 to 6 goals per patient) for patients on galantamine compared to placebo (change from baseline score 4.8 [SD 9.6] v. 0.9 [SD 9.5]; SRM = 0.41, p = 0.02).
The rating by patients and caregivers was not statistically different between treatment groups (change from baseline score 4.2 [SD 10.6] v. 2.3 [SD 9.0], SRM = 0.20, p = 0.27). The accompanying editorial by H. Kaduszkiewicz (ref. 2) acknowledged the feasibility of using the GAS as an outcome measure in clinical trials of anti-dementia drugs.
The point of this month's commented article is that clinicians must rely on patients and caregivers feedback to assess response to symptomatic drugs in mild to moderate AD, and ask about common symptoms of that stage of disease, including verbal repetition. In later stages, agitation and aggression (both verbal and physical) will be important target symptoms, potentially responsive to the other drug class for AD, the NMDA receptor antagonist memantine.
Improvements in such target symptoms are more useful to assess treatment benefits than improvement in MMSE scores, at least with the drugs currently available.
References
1. Rockwood K, Fay S, Song X, MacKnight C, Gorman M; Video-Imaging Synthesis of Treating Alzheimer's Disease (VISTA) Investigators. Attainment of treatment goals by people with Alzheimer's disease receiving galantamine: a randomized controlled trial. CMAJ 2006;174(8); 1099-2105. [Epub 2006 Mar 22]. Free full text article
2. Kaduszkiewicz H. An innovative approach to involve patients in measuring treatment effects in drug trials. CMAJ 2006; 174 (8); 1117-1118. [Epub 2006 Mar 22]. Free full text article