Background: Galantamine has emerged from a large preclinical and clinical research program as a potent new drug for the treatment of Alzheimer’s disease (AD). Different from other drugs used in AD, galantamine, a modest acetylcholinesterase inhibitor, has shown unique modulating effects on the brain’s nicotinic receptors (nAChRs) and several other neurotransmitter systems.
Objective: A high-resolution positron emission tomography (PET) was performed to measure the regional cerebral metabolic rates for glucose (rCMRgIc) in a galantamine treated AD patient such as to determine the cerebral effects of the drug in vivo.
Design: A 72 year old, female with memory complaints over 1 year and subsequently confirmed AD diagnosis was treated with galantamine 4mg bid. over 5 weeks.
Materials and Methods: Prior to and following the 5-week treatment the patient’s glucose utilization (rCMRgIc) and the AChE activity were measured with an ECAT Exact PET Scan, using C11-MP4A as a tracer. Dementia severity was assessed by MMSE and further neuropsychological tests were performed for short-term and long-term verbal memory functions such as for the visuo-spatial skills.
Results: After 5 week galantamine 4mg bid. the cognitive deficits had slightly improved as reported by the patient and confirmed by the neuropsychological test results. The AChE activity, measured by C11-MP4A-PET, displayed about 20% AChE inhibition after galantamine application, i.e. a marked decrease in tracer activity compared to the assessment before treatment. The rCMRgIc analysis (“FDG-PET”) demonstrated a marked increase in glucose metabolism in frontal and temporo-parietal areas. The increase of glucose utilization together with the concomitant clinical improvement are unlikely to be due to the modest AChE inhibition level of the drug, indicating that other mechanisms may be involved in the restoration of cholinergic and metabolic activity. We postulate that the increased glucose metabolism is linked to nAChR stimulation by galantamine which has been shown to act as allosteric enhancer of nicotinic neurotransmission.
Conclusion: The distinct increase of rCMRgIc observed following treatment with the modest AchE inhibitor galantamine suggests a nicotinic stimulation that leads to channel activation, higher Ca-permeability and consequently to a neurotrophic response including stimulation of gene transcription and protein biosynthesis. Further studies are required to solidly establish a neuroprotective effect of galantamine in AD patients and MCI.
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