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O3‐06–08: The therapeutic effect of donepezil on attention and executive function in patients with Parkinson's disease dementia (PDD)
Author(s) -
Swartz Jina E.,
Moline Margaret L.,
Gray Julian,
Thomas Gail,
Harre Mark,
Hsu Timothy
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.457
Subject(s) - donepezil , dementia , verbal fluency test , psychology , executive dysfunction , population , dementia with lewy bodies , rivastigmine , placebo , psychiatry , cognition , medicine , disease , neuropsychology , pathology , alternative medicine , environmental health
Background: The loss of cholinergic neurotransmission has been associated with impairments in attention, memory and executive function several conditions with prominent cognitive difficulties, including dementias (Alzheimer’s disease, Lewy body and Parkinson’s dementia) and schizophrenia, among others. Anticholinergic therapy has been demonstrated to worsen these domains in both demented and normal individuals. Using therapeutic agents such as cholinesterase inhibitors to enhance cholinergic function represents a rational treatment strategy. Domains such as executive function and attention mediated by cholinergic pathways may particularly benefit. The study reported here evaluated donepezil in patients with Parkinson’s disease dementia on several measures of executive function. Methods: Design: 24-week, multi-centre, randomised, double-blind, 3-arm parallel groups, balanced randomisation (placebo, 5 mg, 10 mg). The 10 mg group received 5 mg for 4 weeks. Inclusion criteria: 40 years, PD (UK Brain Bank criteria); Mild moderate dementia (DSM-IV criteria) one year from PD onset; MMSE 10-26; Co-primary outcomes: ADAS-Cog; CIBIC ; Secondary outcomes related to executive function: Brief Test of Attention; D-KEFS Verbal Fluency (including letter fluency, category fluency and category switching); Secondary outcome related to cognition: MMSE; and Analysis population: ITT-LOCF. Results: 550 subjects were randomised (5 mg, n 195; 10 mg, n 182; placebo, n 173). Co-primary outcomes have been reported previously. Statistically significant cognitive improvement (change from baseline to endpoint) was observed on secondary measures of executive function and attention, including the MMSE (p 0.001), Brief Test of Attention and the components of the D-KEFS verbal fluency test (all p 0.01). Both active treatment groups tended to improve, while the placebo group tended to worsen. Both 5 mg and 10 mg were significant compared to placebo, and there was no statistical difference between the donepezil groups. Donepezil was generally well tolerated. Adverse events were consistent with the known safety profile. There were no notable differences between groups in the frequency or nature of serious adverse events or in UPDRS Part III scores. Conclusions: Donepezil appears effective in treating deficits in executive functioning and attention in patients with mild to moderately severe dementia associated with PD.