Cholinergic deficit and response to donepezil therapy in Parkinson's disease with dementia.
ABSTRACT Background: Although donepezil, an acetylcholinesterase inhibitor, has been proved to be effective in ameliorating cognitive impairment in Parkinson's disease with dementia (PDD), the responsiveness of patients to donepezil therapy varies. [5-(11)C-methoxy]donepezil, the radiolabeled form of donepezil, is a ligand for positron emission tomography (PET), which can be exploited for the quantitative analysis of donepezil binding to acetylcholinesterase and for cholinergic imaging. Objectives: To investigate the deficits of the cholinergic system in the brain in PDD and its association with response to donepezil therapy. Methods: Twelve patients with PDD and 13 normal control subjects underwent [5-(11)C-methoxy]donepezil-PET imaging. For patients with PDD, daily administration of donepezil was started after [5-(11)C-methoxy]donepezil-PET imaging and continued for 3 months. Results: In the PDD group, the mean total distribution volume of the cerebral cortices was 22.7% lower than that of the normal control group. The mean total distribution volume of the patients with PDD was significantly correlated with improvement of visuoperceptual function after 3 months of donepezil therapy. Conclusion: The results suggest that donepezil therapy is more effective in patients with less decrease in acetylcholinesterase, a binding site of donepezil, at least in the specific cognitive domain.
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ABSTRACT: Cognitive impairment is a frequent complication of Parkinson's disease (PD). Mild cognitive impairment (MCI) may progress to dementia more frequently and rapidly. PD dementia (PDD) and PD-MCI have a mean prevalence up to 75% each; a four- to six-times increased incidence rate compared with controls. Recent diagnostic clinical criteria for both PDD and PD-MCI require validation. Cognitive decline in PD can be probed clinically, comprehensive neuropsychological assessment being the best way to define it. Neuroimaging in both disorders revealed cortical atrophy, hypometabolism, white matter changes, dopaminergic/cholinergic dysfunction and increased amyloid burden. Combined analysis of imaging and cerebrospinal fluid markers (tau and Aβ-42) is the most promising method for indentifying PD-MCI and PDD. Morphological substrates are a combination of Lewy and Alzheimer pathologies causing destruction of essential neuronal networks. PDD and dementia with Lewy bodies are considered similar parts of a disease spectrum. Treatment with cholinesterase inhibitors revealed mild-to-moderate results.Expert Review of Neurotherapeutics 12/2012; 12(12):1451-66. · 2.96 Impact Factor