title: 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.
  
  
  METHODS
  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.affiliation: Department of Psychiatry, McLean Hospital, Belmont, MA 02178, USA. asatlin@warren.med.harvard.edu
authors.forename: A
authors.initials: A
authors.lastname: Satlin
authors.forename: N
authors.initials: N
authors.lastname: Bodick
authors.forename: W W
authors.initials: WW
authors.lastname: Offen
authors.forename: P F
authors.initials: PF
authors.lastname: Renshaw
mesh_terms: D000109:Acetylcholine / Q000096:biosynthesis; D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005625:Frontal Lobe / Q000378:metabolism; D005997:Glycerylphosphorylcholine / Q000008:administration & dosage / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D009474:Neurons / Q000378:metabolism; D010275:Parasympathetic Nervous System / Q000378:metabolism; D011522:Protons; D011725:Pyridines / Q000627:therapeutic use*; D013830:Thiadiazoles / Q000627:therapeutic use*
chemical_list: D018727:Muscarinic Antagonists; D011522:Protons; D011725:Pyridines; D013830:Thiadiazoles; D005997:Glycerylphosphorylcholine; C075257:xanomeline; D003401:Creatine; D002794:Choline; D000109:Acetylcholine