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Am J Psychiatry 1997; 154:1459-1461
Copyright © 1997 by American Psychiatric Association
Brain proton magnetic resonance spectroscopy (1H-MRS) in Alzheimer's disease: changes after treatment with xanomeline, an M1 selective cholinergic agonist
A Satlin, N Bodick, WW Offen and PF Renshaw
Department of Psychiatry, McLean Hospital, Belmont, MA 02178, USA. asatlin@warren.med.harvard.edu
OBJECTIVE: Higher than normal cellular levels of the phospholipid catabolic
intermediate glycerophosphocholine have been found in postmortem brain
tissue of persons with Alzheimer's disease. Proton magnetic resonance
spectroscopy (1H-MRS) can detect a choline resonance that is largely due to
glycerophosphocholine. The authors tested the hypothesis that treatment
with xanomeline, an M1 selective muscarinic cholinergic agonist, would be
associated with a decrease in the 1H-MRS choline resonance. METHOD:
Patients with mild to moderate Alzheimer's disease received placebo or
xanomeline for 6 months. 1H-MRS spectra were collected at baseline and
after treatment discontinuation for 12 patients, two taking placebo and 10
taking xanomeline at a dose of 25 mg t.i.d. (N = 4), 50 mg t.i.d. (N = 3),
or 75 mg t.i.d. (N = 3). RESULTS: For the combined group of patients taking
xanomeline, there was a significant decrease in the choline/creatine ratio
from baseline to endpoint. CONCLUSIONS: Treatment of Alzheimer's disease
with a cholinergic agonist is associated with a decrease in the MRS choline
resonance. Xanomeline may reduce breakdown of cholinergic neuron membranes
by reducing the cellular requirement for free choline for acetylcholine
synthesis.
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