• Natalie E Allen, Colleen G Canning, Lorena Rosa S Almeida, Bastiaan R Bloem, Samyra Hj Keus, Niklas Löfgren, Alice Nieuwboer, Geert Saf Verheyden, Tiê P Yamato, and Catherine Sherrington.
• Sydney School of Health Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
• Cochrane Db Syst Rev. 2022 Jun 6; 6 (6): CD011574CD011574.

BackgroundMost people with Parkinson's disease (PD) experience at least one fall during the course of their disease. Several interventions designed to reduce falls have been studied. An up-to-date synthesis of evidence for interventions to reduce falls in people with PD will assist with informed decisions regarding fall-prevention interventions for people with PD.ObjectivesTo assess the effects of interventions designed to reduce falls in people with PD.Search MethodsCENTRAL, MEDLINE, Embase, four other databases and two trials registers were searched on 16 July 2020, together with reference checking, citation searching and contact with study authors to identify additional studies. We also conducted a top-up search on 13 October 2021.Selection CriteriaWe included randomised controlled trials (RCTs) of interventions that aimed to reduce falls in people with PD and reported the effect on falls. We excluded interventions that aimed to reduce falls due to syncope.Data Collection And AnalysisWe used standard Cochrane Review procedures. Primary outcomes were rate of falls and number of people who fell at least once. Secondary outcomes were the number of people sustaining one or more fall-related fractures, quality of life, adverse events and economic outcomes. The certainty of the evidence was assessed using GRADE.Main ResultsThis review includes 32 studies with 3370 participants randomised. We included 25 studies of exercise interventions (2700 participants), three studies of medication interventions (242 participants), one study of fall-prevention education (53 participants) and three studies of exercise plus education (375 participants). Overall, participants in the exercise trials and the exercise plus education trials had mild to moderate PD, while participants in the medication trials included those with more advanced disease. All studies had a high or unclear risk of bias in one or more items. Illustrative risks demonstrating the absolute impact of each intervention are presented in the summary of findings tables. Twelve studies compared exercise (all types) with a control intervention (an intervention not thought to reduce falls, such as usual care or sham exercise) in people with mild to moderate PD. Exercise probably reduces the rate of falls by 26% (rate ratio (RaR) 0.74, 95% confidence interval (CI) 0.63 to 0.87; 1456 participants, 12 studies; moderate-certainty evidence). Exercise probably slightly reduces the number of people experiencing one or more falls by 10% (risk ratio (RR) 0.90, 95% CI 0.80 to 1.00; 932 participants, 9 studies; moderate-certainty evidence).  We are uncertain whether exercise makes little or no difference to the number of people experiencing one or more fall-related fractures (RR 0.57, 95% CI 0.28 to 1.17; 989 participants, 5 studies; very low-certainty evidence). Exercise may slightly improve health-related quality of life immediately following the intervention (standardised mean difference (SMD) -0.17, 95% CI -0.36 to 0.01; 951 participants, 5 studies; low-certainty evidence). We are uncertain whether exercise has an effect on adverse events or whether exercise is a cost-effective intervention for fall prevention. Three studies trialled a cholinesterase inhibitor (rivastigmine or donepezil). Cholinesterase inhibitors may reduce the rate of falls by 50% (RaR 0.50, 95% CI 0.44 to 0.58; 229 participants, 3 studies; low-certainty evidence). However, we are uncertain if this medication makes little or no difference to the number of people experiencing one or more falls (RR 1.01, 95% CI 0.90 to 1.14230 participants, 3 studies) and to health-related quality of life (EQ5D Thermometer mean difference (MD) 3.00, 95% CI -3.06 to 9.06; very low-certainty evidence). Cholinesterase inhibitors may increase the rate of non fall-related adverse events by 60% (RaR 1.60, 95% CI 1.28 to 2.01; 175 participants, 2 studies; low-certainty evidence). Most adverse events were mild and transient in nature.  No data was available regarding the cost-effectiveness of medication for fall prevention. We are uncertain of the effect of education compared to a control intervention on the number of people who fell at least once (RR 10.89, 95% CI 1.26 to 94.03; 53 participants, 1 study; very low-certainty evidence), and no data were available for the other outcomes of interest for this comparisonWe are also uncertain (very low-certainty evidence) whether exercise combined with education makes little or no difference to the number of falls (RaR 0.46, 95% CI 0.12 to 1.85; 320 participants, 2 studies), the number of people sustaining fall-related fractures (RR 1.45, 95% CI 0.40 to 5.32,320 participants, 2 studies), or health-related quality of life (PDQ39 MD 0.05, 95% CI -3.12 to 3.23, 305 participants, 2 studies). Exercise plus education may make little or no difference to the number of people experiencing one or more falls (RR 0.89, 95% CI 0.75 to 1.07; 352 participants, 3 studies; low-certainty evidence). We are uncertain whether exercise combined with education has an effect on adverse events or is a cost-effective intervention for fall prevention.  AUTHORS' CONCLUSIONS: Exercise interventions probably reduce the rate of falls, and probably slightly reduce the number of people falling in people with mild to moderate PD.  Cholinesterase inhibitors may reduce the rate of falls, but we are uncertain if they have an effect on the number of people falling. The decision to use these medications needs to be balanced against the risk of non fall-related adverse events, though these adverse events were predominantly mild or transient in nature. Further research in the form of large, high-quality RCTs are required to determine the relative impact of different types of exercise and different levels of supervision on falls, and how this could be influenced by disease severity. Further work is also needed to increase the certainty of the effects of medication and further explore falls prevention education interventions both delivered alone and in combination with exercise.Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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