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

In-vivo metabolic measures with positron emission tomography using (18)-flu orodeoxyglucose (FDG-PET) have demonstrated hypometabolism in temporal, fro ntal, and hippocampal areas during the early stages of Alzheimer's disease (AD). Progression of the dementia in AD involves compromised cholinergic fu nctioning. Cholinesterase inhibitors have demonstrated efficacy in improvin g cognition and behaviour in AD. In this study, we demonstrate the usefulne ss of FDG-PET in measuring the progression of untreated AD and its modifica tion 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-Men tal 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 p atients at baseline and following 26 wk of treatment using the Snodgrass Pi cture Naming activation task. A total of 71.4% of the patients treated with placebo deteriorated clinically compared to only 25.0% of the patients tre ated with rivastigmine (chi (2) = 4.8; p < 0.03). Rivastigmine-responders ( i.e. those who clinically improved or remained clinically stable as measure d by the Clinician's Interview-Based Impression of Change-plus) showed a ma rked increase in brain metabolism (p < 0.01) involving, but not limited to, structures comprising the memory-related cortices and the prefrontal syste m. These metabolic changes were not observed in the placebo-treated patient s or the rivastigmine nonresponders. Of note is that responders increased h ippocampal metabolism by 32.5 % (p < 0.03) compared to a non-significant de crease in the non-responders (6.4%) and placebo-treated patients (4.1%). Th ese results are consistent with the literature suggesting that FDG-PET can sensitively measure the progression of AD and its improvement with cholines terase inhibitors. Rivastigmine prevented the expected deterioration in cli nical status and dramatically increased brain metabolic activity in a major ity of patients.