TITLE:
Effects of Cholinesterase Inhibitors in Cognition on Parkinson’s Disease Dementia: A Systematic Review and Meta-Analysis
AUTHORS:
Marina Martorelli, Larissa Monteiro, Ailton Melo
KEYWORDS:
Parkinson’s Disease, Dementia, Cognitive Impairment, Cholinesterase Inhibitors, Cognition, Non-Motor Symptoms
JOURNAL NAME:
Advances in Parkinson's Disease,
Vol.4 No.4,
November
19,
2015
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.