title: Cholinesterase inhibitors for Parkinson's disease: a systematic review and meta-analysis.
abstract: BACKGROUND
  Parkinson's disease (PD) is a progressive neurodegenerative movement disorder frequently associated with a wide variety of non-motor symptoms related to non-dopaminergic pathways. Although the depletion of dopamine is the key neurochemical impairment in PD and anticholinergic medications are used for symptomatic treatment, significant deficits in cholinergic transmission are also present and have been associated with cognitive decline and gait dysfunction. Therefore, use of a cholinesterase inhibitor (ChI) might improve cognitive function and reduce the risk of falls in patients with PD, although it could plausibly worsen motor features. Our objective was to conduct a systematic review of prospective, randomised controlled trials, in order to assess the efficacy and safety of ChIs compared with placebo in patients with PD.
  
  
  RESULTS
  MEDLINE, Web of Science, CENTRAL and Scopus databases were searched to identify studies published before 5 May 2014 and including patients with PD treated with ChIs. From 945 references identified and screened, 19 were assessed for eligibility and 4 trials were included for a total of 941 patients with PD. ChIs significantly slowed Mini-Mental State Examination decline without effect on risk of falls. Tremor rates and adverse drug reactions favoured the placebo group. Alzheimer Disease Assessment Scale-cognitive subscale, global assessment and behavioural disturbance improved in the ChI group without effect on disability. There was no significant difference between the groups for Unified Parkinson Disease Rating Scale III. A significantly reduced death rate was observed in the treated cohort as compared with placebo.
  
  
  CONCLUSIONS
  ChIs are effective in the treatment of cognitive impairment in patients with PD, but do not affect risk of falls. The choice of treatment has to be balanced considering the increased tremor and adverse drug reactions.
authors.affiliation: Department of Medicine and Health Sciences, School of Medicine, University of Molise, Campobasso, Italy Department of Translational Medical Sciences, Federico II University of Naples, Naples, Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Pagano
authors.affiliation: Salvatore Maugeri Foundation, IRCCS Institute of Telese Terme, Telese Terme, Benevento, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rengo
authors.affiliation: Geriatrics Unit, University of Pisa, Pisa, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pasqualetti
authors.affiliation: Department of Translational Medical Sciences, Federico II University of Naples, Naples, Italy.
authors.forename: Grazia Daniela
authors.initials: GD
authors.lastname: Femminella
authors.affiliation: Geriatrics Unit, University of Pisa, Pisa, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Monzani
authors.affiliation: Department of Translational Medical Sciences, Federico II University of Naples, Naples, Italy Salvatore Maugeri Foundation, IRCCS Institute of Telese Terme, Telese Terme, Benevento, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Ferrara
authors.affiliation: Department of Neurology, Cedar-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Tagliati
mesh_terms: D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D010300:Parkinson Disease / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D002800:Cholinesterase Inhibitors
keywords: DEMENTIA; GAIT; META-ANALYSIS; PARKINSON'S DISEASE