Background: Alzheimer's disease (AD) and vascular dementia (VaD) are the 2 most common forms of dementia, and there is considerable overlap between these conditions in terms of clinical signs and symptoms (eg, cognitive, functional, behavorial). The relationship between cholinergic dysfunction and cognitive and functional impairment in patients with VaD and AD with concomitant cerebrovascular disease (AD + CVD) suggests a potential role for acetylcholinesterase inhibitor (AChEI) therapy.
Galantamine is a novel agent that is both an AChEI and allosteric modulator of nicotinic acetylcholine receptors. Galantamine has demonstrated sustained benefits on cognition, global function, activities of daily living, behavior, and caregiver burden in patients with mild-to-moderate AD.
Methods: In a double-blind, multicenter trial, patients (N = 592) diagnosed with AD + CVD or VaD were randomized to receive galantamine 24 mg/day (n = 396) or placebo (n = 196) for 6 months. All patients were eligible to enter a 6-month, galantamine-only, open-label extension (OLE). Primary endpoints were safety, tolerability, and change in cognition (measured using the Alzheimer's Disease Assessment Scale–cognitive subscale [ADAS-cog]). Patients who completed the 12-month study (n = 326) were eligible to enter a further 24-month OLE.
Results: In a 12-month interim investigation of the 2-year OLE, both treatment groups showed similar rates of decline over the first 12 months of the 24-month extension study (4.3 points and 4.2 points in the GAL/GAL/GAL and PLA/GAL/GAL groups, respectively). Changes from baseline (start of double-blind therapy in the previous study) are smaller than changes from the initial visit of the current study, as they reflect the initial improvement in cognitive function with galantamine therapy observed in the earlier trials. When analyzed separately, patients with VaD maintained cognitive abilities better than patients with AD + CVD (mean change from baseline of 0.8 ± 8.02 [95% CI, –0.8, 2.5] among patients with VaD vs 4.4 ± 9.24 [95% CI 2.7, 6.0] among patients with AD + CVD). In patients with VaD, cognition was maintained above baseline levels for approximately 21 months and was not statistically significantly different from baseline at 24 months. In patients with AD + CVD, cognition was maintained above baseline levels for 12 months. The most frequently reported adverse events, characteristic of an elderly population with dementia, included depression (13%), agitation (12%), and insomnia (11%). Gastrointestinal adverse events were less common than in the initial study, indicating a decline in incidence with long-term therapy.
Conclusions: Galantamine was safe and demonstrated broad clinical efficacy by maintaining cognitive abilities in patients with AD + CVD or VaD for at least 24 months compared with baseline levels.
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