Abstract

Patients with mild-to-moderate Alzheimer disease received transdermal xanomeline, an M1-selective cholinergic agonist, or placebo for 4 months. Clinical assessments and proton magnetic resonance spectroscopic imaging examinations were carried out at baseline, and after 8 and 16 weeks of treatment. There was a positive correlation between change from baseline in parietal lobe gray-matter cytosolic choline, expressed in terms of choline/creatine resonance ratios, and cognitive performance as measured with the Alzheimer's Disease Assessment Scale Cognitive Subscale. Specifically, increased levels of cytosolic choline, a precursor pool for acetylcholine synthesis, were associated with greater progression in memory impairment during treatment.