Acute response to cholinergic challenge predicts long-term response to galantamine treatment in patients with Alzheimer's Disease

Abstract

Cholinesterase inhibitors have been shown to improve cognitive functioning in patients with Alzheimer’s Disease (AD), but are associated with side effects and only 20-40% of the patients clinically improve. In this study, we aimed to investigate the acute pharmacodynamic (PD) effects of a single dose of galantamine on CNS functioning in mild to moderate AD patients and its potential to predict long-term treatment response. This study consisted of a challenge phase, in which a single dose of 16 mg galantamine was administered to 50 mild to moderate AD patients in a double-blind, placebo-controlled cross-over fashion. Acute PD effects were monitored with use of a CNS test battery. In the subsequent treatment phase of the study, patients were treated with open-label galantamine according to regular care. After 6 months of galantamine treatment, patients were categorized as either responder or as non-responder based on their MMSE, NPI and DAD scores. An analysis of covariance was performed to study the difference in acute PD effects between responders and non-responders. Acute decreases of absolute frontal alpha (-20.4; 95%CI=-31.6,-7.47; p=.0046), beta (-15.7; 95% CI=-28.3,-0.93; p=.0390) and theta (-25.9; 95%CI=-38.4,-10.9; p=.0024) EEG parameters and of relative frontal theta power (-3.27%; 95%CI=-5.96,-0.58; p=.0187) on EEG after a single dose administration of galantamine significantly distinguished long-term treatment responders (n=11) from non-responders (n=32) after 6 months. This study demonstrates that patients who demonstrate a reduction in EEG power in the alpha and theta frequency after a single administration of galantamine 16 mg will most likely respond to treatment.