title: Brain metabolic and clinical effects of rivastigmine in Alzheimer's disease.
abstract: In-vivo metabolic measures with positron emission tomography using (18)F-fluorodeoxyglucose (FDG-PET) have demonstrated hypometabolism in temporal, frontal, and hippocampal areas during the early stages of Alzheimer's disease (AD). Progression of the dementia in AD involves compromised cholinergic functioning. Cholinesterase inhibitors have demonstrated efficacy in improving cognition and behaviour in AD. In this study, we demonstrate the usefulness of FDG-PET in measuring the progression of untreated AD and its modification by treatment with rivastigmine (Exelon, Novartis Pharmaceuticals, East Hanover, New Jersey, USA), a centrally selective cholinesterase inhibitor of the carbamate type. Patients with mild to moderate probable AD (Mini-Mental Status Exam scores of 10-26, inclusive) were enrolled in a double-blind, placebo controlled comparison of three fixed daily doses of rivastigmine (3, 6, or 9 mg/d) or placebo for 26 wk. FDG-PET scans were obtained on 27 patients at baseline and following 26 wk of treatment using the Snodgrass Picture Naming activation task. A total of 71.4% of the patients treated with placebo deteriorated clinically compared to only 25.0% of the patients treated with rivastigmine (chi2 = 4.8; p & 0.03). Rivastigmine-responders (i.e. those who clinically improved or remained clinically stable as measured by the Clinicianaposs Interview-Based Impression of Change-plus) showed a marked increase in brain metabolism (p <0.01) involving, but not limited to, structures comprising the memory-related cortices and the prefrontal system. These metabolic changes were not observed in the placebo-treated patients or the rivastigmine non-responders. Of note is that responders increased hippocampal metabolism by 32.5% (p < 0.03) compared to a non-significant decrease in the non-responders (6.4%) and placebo-treated patients (4.1%). These results are consistent with the literature suggesting that FDG-PET can sensitively measure the progression of AD and its improvement with cholinesterase inhibitors. Rivastigmine prevented the expected deterioration in clinical status and dramatically increased brain metabolic activity in a majority of patients.
authors.affiliation: Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92627-3960, USA. sgpotkin@uci.edu
authors.forename: S G
authors.initials: SG
authors.lastname: Potkin
authors.forename: R
authors.initials: R
authors.lastname: Anand
authors.forename: K
authors.initials: K
authors.lastname: Fleming
authors.forename: G
authors.initials: G
authors.lastname: Alva
authors.forename: D
authors.initials: D
authors.lastname: Keator
authors.forename: D
authors.initials: D
authors.lastname: Carreon
authors.forename: J
authors.initials: J
authors.lastname: Messina
authors.forename: J C
authors.initials: JC
authors.lastname: Wu
authors.forename: R
authors.initials: R
authors.lastname: Hartman
authors.forename: J H
authors.initials: JH
authors.lastname: Fallon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging; D001923:Brain Chemistry / Q000187:drug effects*; D002219:Carbamates / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D048448:Phenylcarbamates; D019275:Radiopharmaceuticals; D000068836:Rivastigmine; D014055:Tomography, Emission-Computed
chemical_list: D002219:Carbamates; D018696:Neuroprotective Agents; D048448:Phenylcarbamates; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D000068836:Rivastigmine