Should ReSPonD change falls prevention in Parkinson's disease?

SUMMARY The ReSPonD trial was a single-centre, double-blind, placebo controlled phase 2 trial to investigate whether the acetylcholinesterase inhibitor rivastigmine would reduce gait variability in Parkinson's disease (PD). 1 A total of 130 patients with PD were randomised to receive twice daily oral rivastigmine or placebo for 32 weeks in a 1:1 ratio. Rivastigmine was uptitrated to a target dose of 12 mg per day over 12 weeks. Inclusion criteria were: at least one fall in the preceding year, ability to walk 18 metres without a walking aid, no previous exposure to acetylcholinesterase inhibitors and importantly no dementia or other neurological, orthopaedic or visual problem that interfered with gait. The primary endpoint was the difference in step time variability between the two groups at 32 weeks. Step time variability was measured with a triaxial accelerometer during three different variations of an 18 metre walking task: normal walking, a simple dual task (walking while naming words beginning with a single letter) and a complex dual task (walking while naming words alternating between two letters). At the end of the study period, the treatment arm had a reduction in step time variability of 28% for normal walking (geometric mean 0·72, 95% CI 0·58–0·88; p = 0·002) and 21% in the simple dual task (0·79; 0·62–0·99; p = 0·045). There was a non-significant trend towards improvement for the complex dual task. Adjusted falls incidence rate ratio was considerably lower in the rivastigmine group (0.55, 95% CI 0.38–0.81; p = 0.002). There was a higher incidence of gastrointestinal side effects 52% vs 18% (predominantly nausea) in the rivastigmine group. The authors concluded that rivastigmine can improve gait stability and might reduce falls in patients with PD, necessitating a phase 3 randomised controlled trial with falls as the primary outcome. OPINION Rivastigmine is a licensed treatment for PD dementia, so clinical application in this patient group is already established. The aetiology of falls in PD is multifactorial. Current approaches to falls prevention in PD with exercise-based interventions have had conflicting outcomes when studied in clinical trials, with some evidence supporting Tai Chi. Given the frequency of and morbidity associated with falls in PD, a pharmacological approach to falls prevention is an attractive prospect. Although dopaminergic depletion is the primary deficit and there is some evidence for improvement in gait variability with levodopa use, 6 falls remain common. Cholinergic impairment in PD may be implicated in …