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 (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.
Kemp
P M
PM
Department of Nuclear Medicine, Southampton University Hospitals Trust, Southampton, UK. paul.kemp@suht.swest.nhs.uk
Holmes
C
C
Hoffmann
S
S
Wilkinson
S
S
Zivanovic
M
M
Thom
J
J
Bolt
L
L
Fleming
J
J
Wilkinson
D G
DG
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000077265:Donepezil; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007189:Indans / Q000494:pharmacology / Q000627:therapeutic use*; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000493:pharmacokinetics*; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D010919:Placebos; D011594:Psychometrics; D011813:Quinuclidinyl Benzilate / Q000493:pharmacokinetics*; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome
D002800:Cholinesterase Inhibitors; D007189:Indans; D007457:Iodine Radioisotopes; D018727:Muscarinic Antagonists; D010880:Piperidines; D010919:Placebos; D011813:Quinuclidinyl Benzilate; D000077265:Donepezil