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.
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.
Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China.
Hui-Fu
HF
Wang
Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China Department of Neurology, Qingdao Municipal Hospital, College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, China.
Jin-Tai
JT
Yu
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
Shao-Wen
SW
Tang
Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China.
Teng
T
Jiang
Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
Chen-Chen
CC
Tan
Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
Xiang-Fei
XF
Meng
Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
Chong
C
Wang
Department of Neurology, Qingdao Municipal Hospital, College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, China.
Meng-Shan
MS
Tan
Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China Department of Neurology, Qingdao Municipal Hospital, College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, China.
Lan
L
Tan
D000978:Antiparkinson Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D020961:Lewy Body Disease / Q000188:drug therapy*; D008559:Memantine / Q000009:adverse effects / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy*
D000978:Antiparkinson Agents; D002800:Cholinesterase Inhibitors; D008559:Memantine
Dementia; LEWY BODY; Neuropharmacology; Parkinson's Disease; Systematic Reviews