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Research paper
Efficacy and safety of cholinesterase inhibitors and memantine in cognitive impairment in Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies: systematic review with meta-analysis and trial sequential analysis
  1. Hui-Fu Wang1,
  2. Jin-Tai Yu1,2,3,
  3. Shao-Wen Tang4,
  4. Teng Jiang1,
  5. Chen-Chen Tan2,
  6. Xiang-Fei Meng2,
  7. Chong Wang2,
  8. Meng-Shan Tan3,
  9. Lan Tan1,2,3
  1. 1Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China
  2. 2Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China
  3. 3Department of Neurology, Qingdao Municipal Hospital, College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, China
  4. 4Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China
  1. Correspondence to Dr Jin-Tai Yu, Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong 266071, China; yu-jintai{at}


Objective Recently, several large randomised controlled trials about the treatments of cognitive impairment or dementia due to Parkinson's disease (CIND-PD or PDD) and dementia with Lewy bodies (DLB) were completed. Here, we systematically reviewed the studies (including the recent reports) to provide updated evidence for the treatments of CIND-PD, PDD and DLB.

Methods We searched Cochrane Dementia and Cognitive Improvement Group Specialised Register, Pubmed, Embase, and other sources for eligible trials. We selected global impression and cognitive function as primary efficacy outcomes, and dropouts and adverse events as safety outcomes. Furthermore, Meta-analysis and trial sequential analysis (TSA) were used here.

Results Ten trials were included in this study. Cholinesterase inhibitors and memantine produced small global efficacy on clinicians’ global impression of change (CGIC), from a weighted mean difference of −0.40 (95% CI −0.77 to −0.03) to −0.65 (95% CI −1.28 to −0.01); however, cholinesterase inhibitors but not memantine significantly improved cognition on Mini-Mental State Examination (MMSE), from 1.04 (95% CI 0.43 to 1.65) to 2.57 (95% CI 0.90 to 4.23). Additionally, both of them had good safety outcomes, although rivastigmine showed an increased risk on adverse events than placebo (risk ratio, RR 1.19, TSA adjusted 95% CI 1.04 to 1.36), these events were usually mild or moderate, and the risk disappeared on serious adverse events.

Conclusions Cholinesterase inhibitors and memantine slightly improve global impression; however, only cholinesterase inhibitors enhance cognitive function. Besides, all the drugs have good safety outcomes. But the limited trials precluded the generalisation of these outcomes.

  • Dementia
  • Parkinson's Disease
  • Neuropharmacology
  • Systematic Reviews

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