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Increased glutamate in the hippocampus after galantamine treatment for Alzheimer disease


Penner, Jacob, Rupsingh, Raul, Smith, Matthew, Wells, Jennie L., Borrie, Michael J., Bartha, Robert


Progress In Neuro-Psychopharmacology & Biological Psychiatry, Volume: 34, No.: 1, Pages.: 104-110

Year of Publication



Galantamine is a cholinesterase inhibitor and allosteric potentiating ligand modulating presynaptic nicotinic acetylcholine receptors that is used in the treatment of Alzheimer disease (AD). The purpose of this study was to determine if galantamine treatment would result in detectable hippocampal metabolite changes that correlated with changes in cognition, as measured by the Mini-Mental State Examination (MMSE) and the Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog). Short echo-time proton magnetic resonance (MR) spectra were acquired from within the right hippocampus of ten patients using a 4 Tesla magnetic resonance imaging (MRI) scanner. Spectra were used to quantify absolute metabolite levels for N-acetylaspartate (NAA), glutamate (Glu), choline (Cho), creatine (Cr), and myo-inositol (mI). Patient scans and cognitive tests were performed before and 4 months after beginning galantamine treatment, which consisted of an 8 mg daily dose for the first month and a 16 mg daily dose for the remaining three months. The levels of Glu, Glu/Cr, and Glu/NAA increased after four months of treatment, while there were no changes in MMSE or ADAS-cog scores. Additionally, changes (Delta) in Glu over the four months (DeltaGlu) correlated with DeltaNAA, and Delta(Glu/Cr) correlated with DeltaMMSE scores. Increased Glu and the ratio of Glu to Cr measured by MR spectroscopy after galantamine treatment were associated with increased cognitive performance. The increase in Glu may be related to the action of galantamine as an allosteric potentiating ligand for presynaptic nicotinic acetylcholine receptors, which increases glutamatergic neurotransmission.; Copyright 2009 Elsevier Inc. All rights reserved.

Bibtex Citation

@article{Penner_2010, doi = {10.1016/j.pnpbp.2009.10.007}, url = {}, year = 2010, month = {feb}, publisher = {Elsevier {BV}}, volume = {34}, number = {1}, pages = {104--110}, author = {Jacob Penner and Raul Rupsingh and Matthew Smith and Jennie L. Wells and Michael J. Borrie and Robert Bartha}, title = {Increased glutamate in the hippocampus after galantamine treatment for Alzheimer disease}, journal = {Progress in Neuro-Psychopharmacology and Biological Psychiatry} }


aged, aged, 80 and over, alzheimer disease, analogs derivatives, aspartic acid, brain mapping, choline, cholinesterase inhibitors, creatine, drug effects, drug therapy, female, galantamine, glutamic acid, hippocampus, humans, inositol, magnetic resonance spectroscopy, male, mental status schedule, metabolism, methods, neuropsychological tests, pathology, pharmacology, regression analysis, therapeutic use

Countries of Study


Types of Dementia

Alzheimer’s Disease

Type of Outcomes


Type of Interventions

Pharmaceutical Interventions

Pharmaceutical Interventions

Anti-Alzheimer medications, e.g.: donezepil, galantamine, rivastigmine, memantime