Attainment of treatment goals by people with Alzheimer's disease receiving galantamine: a randomized controlled trial

Abstract

Background: Although cholinesterase inhibitors have produced statistically significant treatment effects, their clinical meaningfulness in Alzheimer's disease is disputed. An important aspect of clinical meaningfulness is the extent to which an intervention meets the goals of treatment.

Methods: In this randomized controlled trial, patients with mild to moderate Alzheimer's disease were treated with either galantamine or placebo for 4 months, followed by a 4-month open-label extension during which all patients received galantamine. The primary outcome measures were Goal Attainment Scaling (GAS) scores from assessments by clinicians and by patients or caregivers of treatment goals set before treatment and evaluated every 2 months. Secondary outcome measures included the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog), the Clinician's Interview-based Impression of Change plus Caregiver Input (CIBIC-plus), the Disability Assessment for Dementia (DAD) and the Caregiving Burden Scale (CBS). To evaluate treatment effect, we calculated effect sizes (as standardized response means [SRMs]) and p values.

Results: Of 159 patients screened, 130 (mean age 77 [standard deviation (SD) 7.7]; 63% women) were enrolled in the study (64 in the galantamine group and 66 in the placebo group); 128 were included in the analysis because they had at least one post-baseline evaluation. In the intention-to-treat analysis, the clinician-rated GAS scores showed a significantly greater improvement in goal attainment among patients in the galantamine group than among those in the placebo group (change from baseline score 4.8 [SD 9.6]) v. 0.9 [SD 9.5] respectively; SRM = 0.41, p = 0.02). The patient- caregiver-rated GAS scores showed a similar improvement in the galantamine group (change from baseline score 4.2 [SD 10.6]); however, because of the improvement also seen in the placebo group (2.3 [SD 9.0]), the difference between groups was not statistically significant (SRM = 0.20, p = 0.27). Of the secondary outcome measures, the ADAS-cog scores differed significantly between groups (SRM = -0.36, p = 0.04), as did the CIBIC-plus scores (SRM = -0.40, p = 0.03); no significant differences were in either the DAD scores (SRM = 0.28, p = 0.13) or the CBS scores (SRM = -0.17, p = 0.38).

Interpretation: Clinicians, but not patients and caregivers, observed a significantly greater improvement in goal attainment among patients with mild to moderate Alzheimer's disease who were taking galantamine than among those who were taking placebo.

Fig. 1: Flow of patients through the study. R = randomization.

Fig. 2: Mean change in GAS (Goal Attainment Scaling) scores among patients with mild to moderate Alzheimer's disease, by treatment group. Top panel: clinician-rated GAS scores. Bottom panel: patient-caregiver–rated GAS scores. Error bars represent 95% confidence intervals. GAL-GAL (black triangles) = patients who received galantamine during both the placebo-controlled phase (months 0–4) and the open-label phase (months 4–8); PLA-GAL (white squares) = patients who received placebo during the placebo-controlled phase and galantamine during the open-label phase. (Missing data were imputed based on the last observation carried forward, excluding baseline data; for the comparison between groups in the open-label phase, only observations in the galantamine group during the placebo-controlled phase were carried forward.)

Fig. 3: Mean change in the ADAS-cog (cognitive subscale of the Alzheimer's Disease Assessment Scale) scores, by treatment group. Error bars represent 95% confidence intervals. See Fig. 2 for description of GAL-GAL (black triangles) and PLA-GAL (white squares) data sets. (Missing data were imputed based on the last observation carried forward, excluding baseline data; for the comparison between groups in the open-label phase, only observations in the galantamine group during the placebo-controlled phase were carried forward.)

Fig. 4: Mean CIBIC-plus (CIinician's Interview-based Impression of Change plus Caregiver Input) scores, by treatment group. Error bars represent 95% confidence intervals. See Fig. 2 for description of GAL-GAL (black triangles) and PLA-GAL (white squares) data sets. (Missing data were imputed based on the last observation carried forward, excluding baseline data; for the comparison between groups in the open-label phase, only observations in the galantamine group during the placebo-controlled phase were carried forward.)