A randomised placebo controlled study to assess the effects of cholinergic treatment on muscarinic receptors in Alzheimer’s disease

Kemp, P.M., Holmes, C., Hoffmann, S., Wilkinson, S., Zivanovic, M., Thom, J., Bolt, L., Fleming, J.S. and Wilkinson, D.G. (2003) A randomised placebo controlled study to assess the effects of cholinergic treatment on muscarinic receptors in Alzheimer’s disease. Journal of Neurology Neurosurgery and Psychiatry, 74 (11), 1567-1570. (doi:10.1136/jnnp.74.11.1567).

Abstract

Objective:to determine the effects of cholinergic treatment on the muscarinic receptor in patients with Alzheimer’s disease.
Methods:12 patients with mild to moderate Alzheimer’s disease and six controls were studied. The patients underwent ADAS-COG psychometric assessment and SPECT brain imaging with 123I quinuclidinyl benzilate (QNB), to demonstrate the postsynaptic muscarinic M1 receptor, before being randomised in a double blind study to receive either an acetylcholinesterase inhibitor (donepezil) or placebo for four months. Following this, the ADAS-COG and the 123I-QNB receptor scan were repeated. The controls were imaged on one occasion only. All image analyses were undertaken using SPM99.
Results:123I-QNB imaging showed a significant relation between baseline psychometric impairment and deficits on scanning. Both placebo and actively treated groups had reductions in 123I-QNB uptake. Greater reductions in receptor binding were demonstrated in the placebo group than in those receiving active treatment. Intraindividual reproducibility of the 123I-QNB imaging technique appeared highly robust.
Conclusions:the results suggest that 123I-QNB uptake is better preserved in Alzheimer’s disease patients on cholinergic treatment than on placebo. Cholinergic treatment may play a neuroprotective role. Sequential 123I-QNB imaging seems to be a powerful tool in monitoring the response of these receptors to disease modifying treatments.

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Contributors

Author: C. Holmes

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