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 (123)I 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 (123)I-QNB receptor scan were repeated. The controls were imaged on one occasion only. All image analyses were undertaken using SPM99. RESULTS: (123)I-QNB imaging showed a significant relation between baseline psychometric impairment and deficits on scanning. Both placebo and actively treated groups had reductions in (123)I-QNB uptake. Greater reductions in receptor binding were demonstrated in the placebo group than in those receiving active treatment. Intraindividual reproducibility of the (123)I-QNB imaging technique appeared highly robust. CONCLUSIONS: The results suggest that (123)I-QNB uptake is better preserved in Alzheimer's disease patients on cholinergic treatment than on placebo. Cholinergic treatment may play a neuroprotective role. Sequential (123)I-QNB imaging seems to be a powerful tool in monitoring the response of these receptors to disease modifying treatments.
RCT Entities:
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 (123)I 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 (123)I-QNB receptor scan were repeated. The controls were imaged on one occasion only. All image analyses were undertaken using SPM99. RESULTS:(123)I-QNB imaging showed a significant relation between baseline psychometric impairment and deficits on scanning. Both placebo and actively treated groups had reductions in (123)I-QNB uptake. Greater reductions in receptor binding were demonstrated in the placebo group than in those receiving active treatment. Intraindividual reproducibility of the (123)I-QNB imaging technique appeared highly robust. CONCLUSIONS: The results suggest that (123)I-QNB uptake is better preserved in Alzheimer's diseasepatients on cholinergic treatment than on placebo. Cholinergic treatment may play a neuroprotective role. Sequential (123)I-QNB imaging seems to be a powerful tool in monitoring the response of these receptors to disease modifying treatments.
Authors: Cassia R Overk; Christian C Felder; Yuan Tu; Doug A Schober; Kelly R Bales; Joanne Wuu; Elliott J Mufson Journal: J Chem Neuroanat Date: 2010-03-27 Impact factor: 3.052
Authors: Pamela E Potter; Paula K Rauschkolb; Yoga Pandya; Lucia I Sue; Marwan N Sabbagh; Douglas G Walker; Thomas G Beach Journal: Acta Neuropathol Date: 2011-05-01 Impact factor: 17.088
Authors: Sanjeet Pakrasi; Sean J Colloby; Michael J Firbank; Elaine K Perry; David J Wyper; Jonathan Owens; Ian G McKeith; E David Williams; John T O'Brien Journal: J Neurol Date: 2007-03-14 Impact factor: 4.849