Cholinesterase inhibitors and memantine for Parkinson's disease dementia and Lewy body dementia: A meta-analysis

Recently, several randomized controlled trials on the use of cholinesterase inhibitors or memantine as treatments for cognitive impairment in Parkinson's disease (CIND-PD), Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) were completed. The present study provided a meta-analysis of these studies to evaluate the efficacy of cholinesterase inhibitors and memantine on CIND-PD, PDD and DLB. The Cochrane Library, Pubmed, Embase and Web of Science databases were searched to retrieve eligible studies. As primary efficacy outcomes, cognitive function, global impression, behavioral symptoms and motor function were selected, while falling and adverse events were regarded as safety outcomes. Of note, domain-specific cognitive function was assessed as a primary efficacy outcome and falling as a safety outcome, which, to the best of our knowledge, has not been studied previously in CIND-PD, PDD and DLB. A total of 15 trials were included in the present meta-analysis. The results revealed that treatment with cholinesterase inhibitors resulted in improvements in cognitive function, the clinician's global impression, behavioral symptoms and motor function, in accordance with the results of previous studies. Furthermore, it was revealed that cholinesterase inhibitors had a significant effect on attention, processing speed, executive functions, memory and language; however, they did not improve visuospatial cognition compared with placebos. Memantine had a significant effect on attention, processing speed and executive functions. In addition, cholinesterase inhibitors and memantine did not significantly reduce falling. It was demonstrated that an increased number of adverse events occurred in the pooled cholinesterase inhibitors and memantine group, compared with that in the placebo group (risk ratio (RR)=1.09; 95% confidence interval (CI): 1.04-1.16; P=0.001); however, in the subgroup analysis, only the rivastigmine group experienced significantly more adverse events than the placebo group (85 vs. 73%; RR=1.18; 95% CI: 1.08-1.29; P=0.0001), but donepezil and memantine did not produce any significant adverse events. In conclusion, cholinesterase inhibitors and memantine have an effect not only on global cognitive function and motor function, but also on attention, processing speed, executive functions, memory and language. However, careful monitoring of the side effects of rivastigmine may be required. Further clinical trials are required to verify these conclusions.