Objective: To determine the effects of cholinergic therapy on the muscarinic receptor in patients with Alzheimer’s disease.
Design: A randomized double-blind placebo-controlled pilot study.
Materials and Methods: 12 patients with mild to moderate AD and 6 controls were studied. The patients underwent ADAS-COG psychometric assessment and SPECT brain imaging with I-123 quinuclidinyl benzilate (QNB), to demonstrate the post-synaptic muscarinic M1 receptor, prior to being randomised in a double-blind study to receive either an acetylcholinesterase inhibitor (donepezil) or placebo for 4 months. Following this time period, the ADAS-COG and the I-123 QNB receptor scan were repeated. All image analyses were undertaken using SPM99.
Results: I-123 QNB imaging demonstrated a significant relationship between baseline psychometric impairment and deficits on scanning. Both placebo and actively treated groups demonstrated significant deleterious changes in their receptor status. Significantly greater reductions in receptor status were demonstrated in the placebo group as compared to those receiving active treatment. Intra-individual reproducibility of the I-123 QNB imaging technique appeared highly robust.
Conclusion: The results of this pilot study suggest that cholinergic therapy in AD may reduce the loss of the muscarinic postsynaptic M1 receptors. Sequential I-123 QNB imaging appears to be a powerful tool in monitoring the response of these receptors to disease modifying therapies.
Back to S030 New Findings in the Pharmacology of Dementia
Back to The Eleventh International Congress