Brain proton magnetic resonance spectroscopy (1H-MRS) in Alzheimer's disease: changes after treatment with xanomeline, an M1 selective cholinergic agonist.

Abstract

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.

• Authors: A Satlin, N Bodick, W W Offen, P F Renshaw
• Journal: The American journal of psychiatry (Am J Psychiatry) Vol. 154 Issue 10 Pg. 1459-61 (Oct 1997) ISSN: 0002-953X [Print] United States
• PMID: 9326834 (Publication Type: Clinical Trial, Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Muscarinic Antagonists
• Protons
• Pyridines
• Thiadiazoles
• Glycerylphosphorylcholine
• xanomeline
• Creatine
• Choline
• Acetylcholine

Topics

• Acetylcholine (biosynthesis)
• Alzheimer Disease (diagnosis, drug therapy, metabolism)
• Brain (metabolism)
• Choline (metabolism)
• Creatine (metabolism)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Frontal Lobe (metabolism)
• Glycerylphosphorylcholine (administration & dosage, metabolism)
• Humans
• Magnetic Resonance Spectroscopy
• Muscarinic Antagonists (administration & dosage, therapeutic use)
• Neurons (metabolism)
• Parasympathetic Nervous System (metabolism)
• Protons
• Pyridines (therapeutic use)
• Thiadiazoles (therapeutic use)