A randomised placebo controlled study to assess the effects of cholinergic treatment on muscarinic receptors in Alzheimer’s disease
- P M Kemp1,
- C Holmes2,
- S Hoffmann3,
- S Wilkinson2,
- M Zivanovic1,
- J Thom1,
- L Bolt3,
- J Fleming3,
- D G Wilkinson2
- 1Department of Nuclear Medicine, Southampton University Hospitals Trust, Southampton, UK
- 2Memory Assessment and Research Centre, Moorgreen Hospital, Southampton
- 3Department of Medical Physics and Bioengineering, Southampton University Hospitals Trust
- Correspondence to: Dr Paul M Kemp, Department of Nuclear Medicine, Southampton University Hospitals Trust, Southampton SO16, 6YD, UK;
- Received 23 December 2002
- Accepted 16 May 2003
- Revised 7 May 2003
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.
Competing interests: Pfizer-Eisai have awarded a project grant to DW and CH, involved them in multicentre trials, and contributed to their expenses for conference presentations.