BRAIN PROTON MAGNETIC-RESONANCE SPECTROSCOPY (H-1-MRS) IN ALZHEIMERS-DISEASE - CHANGES AFTER TREATMENT WITH XANOMELINE, AN M-1 SELECTIVE CHOLINERGIC AGONIST

Objective: Higher than normal cellular levels of the phospholipid cata bolic intermediate glycerophosphocholine have been found in postmortem brain tissue of persons with Alzheimer's disease. Proton magnetic res onance spectroscopy (H-1-MRS) can detect a choline resonance that is l argely due to glycerophosphocholine. The authors tested the hypothesis that treatment with xanomeline, an M-1 selective muscarinic cholinerg ic agonist, would be associated with a decrease in the H-1-MRS choline resonance. Method. Patients with mild to moderate Alzheimer's disease received placebo or xanomeline for 6 months. H-1-MRS spectra were col lected 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 signifi cant decrease in the choline/creatine ratio from baseline to endpoint. Conclusions: Treatment of Alzheimer's disease with a cholinergic agon ist is associated with a decrease in the MRS choline resonance. Xanome line may reduce breakdown of cholinergic neuron membranes by reducing the cellular requirement for free choline for acetylcholine synthesis.