Abstract
Introduction: Dementia is frequently associated with Parkinson’s disease, especially in later stages. Efficacy of cholinesterase inhibitors (ChI) in Alzheimer’s dementia is well established. However, treatment with ChI in Parkinson’s disease dementia (PDD) remains controversial. The objective of this systematic review and meta-analysis was to assess the effects of ChI in PDD. Methods: A comprehensive literature search was performed in MEDLINE, EMBASE and Cochrane library up to March 2014 using the descriptors “Parkinson’s disease”, “dementia in Parkinson’s disease”, “cognition”, “acetylcholinesterase inhibitors”, “cholinesterase inhibitors”, “anticholinesterase agents”, “rivastigmine”, “donepezil” and “galantamine” (Pubmed search strategy). All randomized, doubleblinded, placebo-controlled trials that met the eligibility criteria and assessed the effects of ChI in PDD were considered for analysis. There were no restrictions regarding paper language. Summary effect-sizes were presented as standardized mean differences (SMD) and the pooled analysis was performed with a fixed-effects model. Outcomes considered for analysis were the Mini Mental Status Exam (MMSE) score and the cognition scale for evaluation of dementia ADAS-Cog. The degree of heterogeneity between included studies was assessed through the I2 test. Results: After a comprehensive search, 175 references were retrieved. From these, five randomized trials involving 946PDD subjects were included in the review. Four studies used donepezil and only one study used rivastigmine. The pooled analysis of five studies that assessed the effects of ChI in MMSE total score showed a SMD of 0.24 (CI 95% 0.11 - 0.38). Three studies considered the effects of ChI on Adas-Cog and the pooled results showed a SMD of 0.21 (CI 95% 0.07 - 0.35). There was no significant heterogeneity between the studies. Conclusions: The results of this systematic review and meta- analysis suggest that ChI improves cognitive impairment in PDD subjects. Despite statistically significant, the translation of these results into relevant clinical improvement should be taken with caution, as the studies did not address what would be considered a clinically significant result.
Highlights
Dementia is frequently associated with Parkinson’s disease, especially in later stages
The criteria to define a clinical diagnosis of Parkinson’s disease dementia (PDD) must include the diagnosis of Parkinson’s disease (PD) according to the United Kingdom Brain Bank criteria and insidious cognition impairment associated with behavioral features, characterized by the presence of attentional deficits, memory and executive function disturbances, visuospatial dysfunction, apathy, humor and personality changes, hallucinations, delirium and excessive daytime sleepiness [8]
A total of five randomized trials [14] [18]-[21], comprising 946 subjects who assessed the effects of cholinesterase inhibitors in PDD were included in the analysis
Summary
Dementia is frequently associated with Parkinson’s disease, especially in later stages. Outcomes considered for analysis were the Mini Mental Status Exam (MMSE) score and the cognition scale for evaluation of dementia ADAS-Cog. The degree of heterogeneity between included studies was assessed through the I2 test. Three studies considered the effects of ChI on Adas-Cog and the pooled results showed a SMD of 0.21 (CI 95% 0.07 - 0.35). Conclusions: The results of this systematic review and meta-analysis suggest that ChI improves cognitive impairment in PDD subjects. The criteria to define a clinical diagnosis of PDD must include the diagnosis of PD according to the United Kingdom Brain Bank criteria and insidious cognition impairment associated with behavioral features, characterized by the presence of attentional deficits, memory and executive function disturbances, visuospatial dysfunction, apathy, humor and personality changes, hallucinations, delirium and excessive daytime sleepiness [8]. According to previous published data, the effect of cholinesterase inhibitors (ChI) on cognition in mild to moderate PDD is the modest [14], and side effects on Parkinsonian symptoms such as rising tremor must be considered [15]
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