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Dubois B.,University Pierre and Marie Curie | Tolosa E.,University of Barcelona | Tolosa E.,French Institute of Health and Medical Research | Katzenschlager R.,Donauspital SMZ Ost | And 9 more authors.
Movement Disorders | Year: 2012

Parkinson's disease dementia (PDD) is associated with cholinergic deficits. This report presents an efficacy and safety study of the acetylcholinesterase inhibitor donepezil hydrochloride in PDD. PDD patients (n = 550) were randomized to donepezil (5 or 10 mg) or placebo for 24 weeks. Coprimary end points were the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Clinician's Interview-Based Impression of Change plus caregiver input (CIBIC+; global function). Secondary end points measured executive function, attention, activities of daily living (ADLs), and behavioral symptoms. Safety and tolerability were assessed. ADAS-cog mean changes from baseline to week 24 (end point) were not significant for donepezil in the intent-to-treat population by the predefined statistical model (difference from placebo: -1.45, P = .050, for 5 mg; -1.45, P = .076, for 10 mg). Alternative ADAS-cog analysis, removing the treatment-by-country interaction term from the model, revealed significant, dose-dependent benefit with donepezil (difference from placebo: -2.08, P = .002, for 5 mg; -3.31, P < .001, for 10 mg). The 10-mg group, but not the 5-mg group, had significantly better CIBIC+ scores compared with placebo (3.7 vs 3.9, P = .113, for 5 mg; 3.6 vs 3.9, P = .040, for 10 mg). Secondary end points-Mini-Mental State Exam; Delis-Kaplan Executive Function System; Brief Test of Attention, representing cognitive functions particularly relevant to PDD-showed significant benefit for both donepezil doses (P ≤ .007). There were no significant differences in ADLs or behavior. Adverse events were more common with donepezil but mostly mild/moderate in severity. Although the study did not achieve its predefined primary end points, it presents evidence suggesting that donepezil can improve cognition, executive function, and global status in PDD. Tolerability was consistent with the known safety profile of donepezil. © 2012 Movement Disorder Society. Source


Katzenschlager R.,Donauspital SMZ Ost
Journal of the Neurological Sciences | Year: 2011

Parkinson's disease (PD) is a progressive neurodegenerative condition which requires gradually increasing doses of dopaminergic substances for adequate motor control. Some vulnerable patients increase their doses beyond those required for motor control. This may result in a pattern of compulsive drug taking which may be associated with typical behavioural changes which define dopaminergic dysregulation syndrome (DDS). This is frequently associated with impulse control disorders and a specific behavioural abnormality involving prolonged repetitive tasks, called punding. The pathophysiology of DDS likely involves a number of factors, including genetic and personality related risk factors, habit formation resulting from unpleasant OFF symptoms, fronto-striatal dysfunction and a sensitisation process due to repeated dopaminergic stimulation. Management includes attempts to reduce the dopaminergic dose; specific treatment options are currently unknown. Early detection and prevention are therefore essential. © 2011 Elsevier B.V. Source

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