PET imaging of the in vivo brain acetylcholinesterase activity and nicotine binding in galantamine-treated patients with AD

Abstract 

The effect of galantamine treatment on cortical acetylcholinesterase (AChE) activity and nicotinic receptor binding was investigated by positron emission tomography (PET) in 18 patients with mild Alzheimer's disease (AD) in relation to galantamine concentration and the patients’ cognitive performances. The first 3 months of the study was of a randomized double-blind placebo-controlled design, during which 12 patients received galantamine (16–24mg/day) and 6 patients the placebo, and this was followed by 9 months’ galantamine treatment in all patients. The patients underwent PET examinations to measure cortical AChE activity (¹¹C-PMP) and ¹¹C-nicotine binding. Neuropsychological tests were performed throughout the study. Inhibition (30–40%) of cortical AChE activity was observed after 3 weeks to 12 months of galantamine treatment. No significant change in mean cortical ¹¹C-nicotine binding was observed during the study. ¹¹C-Nicotine binding, however, positively correlated with plasma galantamine concentration. Both the changes of AChE activity and ¹¹C-nicotine binding correlated positively with the results of a cognitive test of attention. In conclusion, galantamine caused sustained AChE inhibition for up to 12 months. At the individual level, the in vivo cortical AChE inhibition and ¹¹C-nicotine binding were associated with changes in the attention domain of cognition rather than episodic memory.

Keywords: Alzheimer's disease, Acetylcholinesterase, ¹¹C-Nicotine binding, Positron emission tomography (PET), Cerebrospinal fluid, Plasma, Cognitive function, Attention, Galantamine