Does the enhancement of cholinergic neurotransmission influence brain glucose kinetics and clinical symptomatology in progressive supranuclear palsy?

Chotinergic systems are markedly affected both in cortical and subcortical cerebral areas of patients with progressive supranuclear palsy(PSP). To determine whether it is possible to modify the clinical picture of PSP through the enhancement of brain cholinergic neurotransmission, we studied the effects of physostigmine, an anticholinesterase reference drug, on symptoms and brain glucose metabolism using (18F)fluorodeoxyglucose (FDG) and PET. Patients were evaluated blind in a randomized order with both placebo and physostigmine infusions after an individual determination of maximal tolerated dose.

Under steady-state physostigmine infusions, although glucose consumption was not significantly modified, the entry of glucose from blood to brain was regionally increased from 8 to 32% of placebo values suggesting an increase in cerebral blood flow (CBF) or an increase in the activity of brain glucose transporter. Following physostigmine administration in the same patients: the errors in ... more.

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