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.
Publication types
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Clinical Trial
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Clinical Trial, Phase III
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Randomized Controlled Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Cutaneous
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Aged
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Aged, 80 and over
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Alzheimer Disease / drug therapy*
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Alzheimer Disease / metabolism
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Brain / metabolism*
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Choline / metabolism
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Cognition / drug effects*
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Creatine / metabolism
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Female
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Humans
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Magnetic Resonance Spectroscopy*
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Male
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Middle Aged
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Muscarinic Agonists / administration & dosage
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Muscarinic Agonists / therapeutic use*
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Psychotropic Drugs / administration & dosage
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Psychotropic Drugs / therapeutic use*
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Pyridines / administration & dosage
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Pyridines / therapeutic use*
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Thiadiazoles / administration & dosage
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Thiadiazoles / therapeutic use*
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Treatment Outcome
Substances
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Muscarinic Agonists
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Psychotropic Drugs
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Pyridines
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Thiadiazoles
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xanomeline
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Creatine
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Choline