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Background: Falls are a common complication of Parkinson's disease. There is a need for new therapeutic options to target this debilitating aspect of the disease. Cholinergic deficit has been shown to contribute to both gait and cognitive dysfunction seen in the condition. Potential benefits of using cholinesterase inhibitors were shown during a single centre phase 2 trial. The aim of this trial is to evaluate the effectiveness of a cholinesterase inhibitor on fall rate in people with idiopathic Parkinson's disease., Methods: This is a multi-centre, double-blind, randomised placebo-controlled trial in 600 people with idiopathic Parkinson's disease (Hoehn and Yahr stages 1 to 4) with a history of a fall in the past year. Participants will be randomised to two groups, receiving either transdermal rivastigmine or identical placebo for 12 months. The primary outcome is the fall rate over 12 months follow-up. Secondary outcome measures, collected at baseline and 12 months either face-to-face or via remote video/telephone assessments, include gait and balance measures, neuropsychiatric indices, Parkinson's motor and non-motor symptoms, quality of life and cost-effectiveness., Discussion: This trial will establish whether cholinesterase inhibitor therapy is effective in preventing falls in Parkinson's disease. If cost-effective, it will alter current management guidelines by offering a new therapeutic option in this high-risk population., Trial Registration: REC reference: 19/SW/0043. EudraCT: 2018-003219-23., Iscrtn: 41639809 (registered 16/04/2019). ClinicalTrials.gov Identifier: NCT04226248 PROTOCOL AT TIME OF PUBLICATION: Version 7.0, 20th January 2021., (© 2021. The Author(s).)

Background: Gait impairments are common in patients with Alzheimer's disease. Cholinesterase inhibitors are used to treat the symptoms of patients with Alzheimer's disease, but they have not been shown to reduce the severity of Alzheimer's disease-related gait disorders., Methods: This was a prospective, single-arm, open-label, non-randomized study. The aim of the present study was to determine the effect of the acetylcholinesterase inhibitor rivastigmine on gait in 21 newly diagnosed patients with mild to moderate Alzheimer's disease. The outcome variables were velocity, stride length, and cadence during single-task and dual-task gait trials. The subjects were also assessed with the Mini-Mental State Examination, Alzheimer's Disease Cooperative Study Activities of Daily Living, Functional Assessment Staging, and Geriatric Depression Scale., Results: After 12 weeks of treatment with rivastigmine, gait velocity was significantly improved in the dual-task gait trials; gait velocity was increased from 40.59 ± 13.59 m/min at baseline to 46.88 ± 12.73 m/min when counting backward from 100 in steps of 7 while walking, and gait velocity was increased from 37.06 ± 15.57 m/min at baseline to 42.03 ± 14.02 m/min when naming animals while walking. In the single-task gait trials, which consisted only of walking at their usual pace or at a fast pace, gait velocity was not increased by rivastigmine administration., Conclusion: Our findings indicated that rivastigmine improved gait in subjects with mild to moderate Alzheimer's disease during dual-task trials. The observed enhancement of dual-task gait might be caused by an improvement of cognitive function rather than motor function., Trial Registration: UMIN, UMIN000025869. Registered December 16, 2016, https://upload.umin.ac.jp/cgi-open-bin/icdr/ctr_view.cgi?recptno=R000029744.

Background: Cholinesterase inhibitors are used to treat the symptoms of dementia and can theoretically cause bradycardia. Previous studies suggest that patients taking these medications have an increased risk of undergoing pacemaker insertion. Since these drugs have a marginal impact on patient outcomes, it might be preferable to change drug treatment rather than implant a pacemaker. This population-based study determined the association of people with dementia exposed to cholinesterase inhibitor medication and pacemaker insertion., Methods: We used data from the Ontario health administrative databases from January 1, 1993 to June 30, 2012. We included all community-dwelling seniors who had a code for dementia and were exposed to cholinesterase inhibitors (donezepil, galantamine, and rivastigmine) and/or drugs used to treat co-morbidities of hypertension, diabetes, depression and hypothyroidism. We controlled for exposure to anti-arrhythmic drugs. Observation started at first exposure to any medication and continued until the earliest of pacemaker insertion, death, or end of study., Results: 2,353,909 people were included with 96,000 (4.1%) undergoing pacemaker insertion during the observation period. Case-control analysis showed that pacemaker patients were less likely to be coded with dementia (unadjusted OR 0.42 [95%CI 0.41-0.42]) or exposed to cholinesterase inhibitors (unadjusted OR 0.39 [95%CI 0.37-0.41]). That Cohort analysis showed patients with dementia taking cholinesterase inhibitors had a decreased risk of pacemaker insertion (unadj-HR 0.58 [0.55-0.61]). Adjustment for patient age, sex, and other medications did not notably change results, as did restricting the analysis to incident users., Conclusions: Patients taking cholinesterase inhibitors rarely undergo, and have a significantly reduced risk of, cardiac pacemaker insertion.