Schizophrenic subjects with predominantly negative symptoms have greater metabolic abnormalities than subjects with predominantly positive symptoms, particularly in frontal, temporal, and cerebellar circuitry. These results are consistent with abnormalities in corticocortical, corticobasal ganglia, mesocortical dopamine, and cerebellar-thalamic-prefrontal circuits, which may underlie the negative symptoms of schizophrenia.
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 71n4 % of the patients treated with placebo deteriorated clinically compared to only 25n0 % of the patients treated with rivastigmine (χ# l 4n8; p 0n03). Rivastigmineresponders (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 0n01) 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 nonresponders. Of note is that responders increased hippocampal metabolism by 32n5% (p 0n03) compared to a non-significant decrease in the non-responders (6n4 %) and placebo-treated patients (4n1 %). 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.
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