Brain metabolic and clinical effects of rivastigmine in Alzheimer’s disease

In-vivo metabolic measures with positron emission tomography using ")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 (v#fl 4–8; p! 0–03). Rivastigmine-responders (i.e. those who clinically improved or remained clinically stable as measured by the Clinician’s Interview-Based Impression of Change-plus) showed a marked increase in brain metabolism (p! 0–01