High field (1)H MRS of the hippocampus after donepezil treatment in Alzheimer disease.
The purpose of this study was to measure metabolite level changes in patients with newly diagnosed Alzheimer Disease (AD) following four months of donepezil treatment. A small number of cognitively normal elderly subjects were also scanned longitudinally (twice within one year) to assess the reproducibility. Short echo-time (1)H magnetic resonance spectra were acquired at 4.0 T in the right hippocampus. Subjects were scanned at the time of first diagnosis (prior to receiving donepezil) and then following four months of donepezil treatment (5 mg/day for the first month, 10 mg/day thereafter). Changes in absolute metabolite levels and metabolite ratios were quantified and compared. There was no change in measured cognitive function following four months of donepezil treatment in the AD patients. Decreased levels of N-acetylaspartate, choline, N-acetylaspartate/creatine, choline/creatine, and myo-inositol/creatine were observed in AD patients after four months of treatment. Cognitively normal elderly subjects showed an increase in myo-inositol/choline ratio following one year. The reduced levels of N-acetylaspartate in AD patients indicates continued decline in neuronal function and/or integrity. However decreased levels of choline and myo-inositol/creatine ratio may indicate a positive treatment effect.
Bartha
Robert
R
Centre for Functional and Metabolic Mapping, Robarts Research Institute, University of Western Ontario, 1151 Richmond Street, Suite 2, London, Ontario, Canada N6A 5B8. rob.bartha@imaging.robarts.ca
Smith
Matthew
M
Rupsingh
Raul
R
Rylett
Jane
J
Wells
Jennie L
JL
Borrie
Michael J
MJ
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D001224:Aspartic Acid / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D002794:Choline / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D003401:Creatine / Q000378:metabolism; D000077265:Donepezil; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007189:Indans / Q000494:pharmacology* / Q000627:therapeutic use; D007294:Inositol / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D011522:Protons
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D011522:Protons; D001224:Aspartic Acid; D007294:Inositol; D000077265:Donepezil; D003401:Creatine; D002794:Choline