Objective: Dementia with Lewy bodies (DLB) is a neurodegenerative disease associated with a central cholinergic deficiency. In addition to dementia, it is manifested by at least 2 of the following features: parkinsonism, visual hallucinations, and/or fluctuations in alertness. The primary objective of this trial were to show at 12 and 24 weeks that a dose of 8–24 mg/day of galantamine is effective in improving behavior, global function, and cognition in DLB patients (vs baseline). Secondary endpoints included safety measures and activities of daily living (ADL).
Design: This open-label, 24-week, multicenter trial was conducted in the United States. An analysis was performed at Week 12. Dosing was escalated using the recommended schedule (galantamine 4 mg bid for 8 weeks, then 8 mg bid for 4 weeks, then 12 mg until study completion at 24 weeks). One dose reduction was allowed.
Materials and Methods: The Neuropsychiatric Inventory (NPI-4 item [depression, delusions, apathy, and hallucinations] and NPI-12 item) scale was used to measure changes in behavior. Cognitive changes were measured by the Alzheimer's Disease Assessment Scale–cognitive subscale (ADAS-cog). The 23-item version of the Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS/ADL) was used to evaluate changes in function. Global functioning was measured by the ADCS–Clinician's Global Impression of Change (ADCS-CGIC). The safety of galantamine also was evaluated.
Results: 19 patients were enrolled (mean age: 76.8 ± 8.2 years; 68.4% male; mean baseline scores: MMSE, 19.84 ± 5.75; ADAS-cog, 25.9 ± 14.0; NPI-12, 20.5; UPDRS, 19.5). Results at 12 weeks indicated a mean change from baseline in NPI-12 of 4.0 points, with a 4.3-point change in NPI-4 (p = 0.02); >70% of patients had a response of >4.0 points. NPI components that improved included delusions, hallucinations, agitation, apathy, night behaviors, depression, and aberrant motor behavior. Patients demonstrated improvement in cognition (ADAS-cog) of 4.8 points, including word recall and word recognition tests. Results at 24 weeks indicated a mean change from baseline in NPI-12 of 12.6 points (SE: 2.8; p = 0.0005), with a 5.8-point change in NPI-4 (SE: 1.3; p = 0.0008). ADAS-cog scores improved by 5.8 points (SE: 2.8) at Week 24 (p = 0.06). There was a 4.9-point improvement in ADL and a 0.5-point improvement in global function at Week 12. At Week 24, there was a 3.71-point (SE: 3.8) improvement in ADL (p > 0.1) and a 0.64-point (SE: 0.29) improvement in global function (p = 0.04). Galantamine was safe and well tolerated. The most frequently reported adverse events were nausea (31.5%) and fatigue (21.0%).
Conclusions: This analysis suggests that galantamine is safe and effective in DLB patients. Retention rates were higher, and adverse events were lower than in previous trials of cholinesterase inhibitors in DLB.
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