Management of patients with Alzheimer's disease plus cerebrovascular disease: 12-month treatment with galantamine. Galantamine treatment of vascular dementia: a randomized trial.
We evaluated the long-term cognitive effects and safety of galantamine 24 mg/day in patients with Alzheimer's disease plus cerebrovascular disease (AD + CVD or mixed dementia). Subgroup analysis was performed of patients with AD + CVD who participated in a 6-month, multicenter, randomized, double-blind, parallel-group study and a 6-month, open-label, active-treatment extension.
                Two hundred and eighty-five patients with AD + CVD were randomized to receive either placebo (n = 97) or galantamine 24 mg/day (n = 188) for 6 months. Two hundred and thirty-eight (84%) patients continued with the open-label phase of the study (86 from the placebo group, 152 from the galantamine group) and were treated with galantamine 24 mg/day. The primary efficacy measure was cognitive performance as assessed using the eleven-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog/11). Standard safety evaluations and adverse-event monitoring were performed throughout the 12-month study period. Patients with AD + CVD treated with galantamine experienced statistically and clinically significant improvement in cognition at month 6 (mean change in ADAS-cog/11 score -1.1; p < or = 0.05 vs. baseline) and maintained their cognitive function for the entire 12-month study (mean change in ADAS-cog/11 score +0.1). In contrast, the cognitive function deteriorated among those in the placebo group (mean change in ADAS-cog/11 at month 6 +2.0; p < or = 0.001 vs. baseline). Patients with AD + CVD who were switched from placebo to galantamine for the open-label phase of the trial did show improvement in cognitive function; however, they never attained the same cognitive level as patients who had been treated with galantamine for the entire 12 months [mean (+/- SE) ADAS-cog/11 scores in the placebo/galantamine group 25.7 +/- 1.32 and 24.2 +/- 1.57 at months 6 and 12, respectively, and in the galantamine/galantamine group 21.5 +/- 0.87 and 22.2 +/- 1.06 at months 6 and 12, respectively]. The results of this subgroup analysis indicate that galantamine is effective for long-term maintenance of the cognitive function in patients with AD + CVD and is safe and well tolerated in this patient population.
                Copyright 2004 S. Karger AG, Basel To evaluate efficacy and safety of galantamine for patients with vascular dementia (VaD).
                In this multinational, randomized, double-blind, placebo-controlled, parallel-group clinical trial, 788 patients with probable VaD who also satisfied strict centrally read MRI criteria were randomized to receive galantamine or placebo. Efficacy was evaluated using measures of cognition, daily function, and behavior. The primary efficacy measures were the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-cog/11) and the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL) total score. Secondary outcomes included the Clinician's Interview Based on Impression of Change-Plus Caregiver Input (CIBIC-plus), Neuropsychiatric Inventory, and EXIT-25 for assessment of executive functioning. Safety and tolerability were also monitored.
                Patients treated with galantamine had a greater improvement in ADAS-cog/11 after 26 weeks compared with placebo (-1.8 vs -0.3; p < 0.001). There was no difference between galantamine and placebo at week 26 on the ADCS-ADL score (0.7 vs 1.3; p = 0.783). Improvement in global functioning measured by the CIBIC-plus associated with galantamine approached significance (p = 0.069). A difference between treatment groups for EXIT-25 favoring galantamine was detected (p = 0.041). Safety data revealed that 13% of galantamine and 6% of placebo patients discontinued treatment because of adverse events.
                Significance was not reached for both co-primary endpoints. Galantamine was effective for improving cognition, including executive function, in patients with vascular dementia, with good safety and tolerability. However, improvement in activities of daily living with galantamine was similar to that observed with placebo.