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

A randomised placebo controlled study to assess the effects of cholinergic treatment on muscarinic receptors in Alzheimer’s disease
A randomised placebo controlled study to assess the effects of cholinergic treatment on muscarinic receptors in Alzheimer’s disease
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.
alzheimer’s disease, quinuclidinyl benzilate, spect
0022-3050
1567-1570
Kemp, P.M.
c982082a-81d9-404a-b2e6-f2eb19cd1163
Holmes, C.
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Hoffmann, S.
b25297be-096e-4cdc-a01c-d6d6c2492705
Wilkinson, S.
515fffa9-1b52-4208-9898-563773dda70a
Zivanovic, M.
04aebbad-3290-4b2a-afe8-050c9e13ed07
Thom, J.
3384d082-5240-4fe7-9abf-2571dcf39400
Bolt, L.
6030050a-498b-4e67-b65e-5575828e1c22
Fleming, J.S.
bf089a52-bc49-402a-9129-0dfecf452936
Wilkinson, D.G.
c6ce3fd6-86d5-454c-82b0-f4a857700eef
Kemp, P.M.
c982082a-81d9-404a-b2e6-f2eb19cd1163
Holmes, C.
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Hoffmann, S.
b25297be-096e-4cdc-a01c-d6d6c2492705
Wilkinson, S.
515fffa9-1b52-4208-9898-563773dda70a
Zivanovic, M.
04aebbad-3290-4b2a-afe8-050c9e13ed07
Thom, J.
3384d082-5240-4fe7-9abf-2571dcf39400
Bolt, L.
6030050a-498b-4e67-b65e-5575828e1c22
Fleming, J.S.
bf089a52-bc49-402a-9129-0dfecf452936
Wilkinson, D.G.
c6ce3fd6-86d5-454c-82b0-f4a857700eef

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).

Record type: Article

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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More information

Published date: 2003
Additional Information: Short Report
Keywords: alzheimer’s disease, quinuclidinyl benzilate, spect

Identifiers

Local EPrints ID: 25707
URI: http://eprints.soton.ac.uk/id/eprint/25707
ISSN: 0022-3050
PURE UUID: 431b8a75-e1c2-4251-9de5-0a853aba8099
ORCID for C. Holmes: ORCID iD orcid.org/0000-0003-1999-6912

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Date deposited: 24 Apr 2006
Last modified: 16 Mar 2024 03:06

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Contributors

Author: P.M. Kemp
Author: C. Holmes ORCID iD
Author: S. Hoffmann
Author: S. Wilkinson
Author: M. Zivanovic
Author: J. Thom
Author: L. Bolt
Author: J.S. Fleming
Author: D.G. Wilkinson

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