Anticholinesterase offers a ‘steadying hand’ to PD patients

By Lucy Piper, Senior medwireNews Reporter

The dementia drug rivastigmine may reduce the risk of falls in patients with Parkinson’s disease (PD) by improving gait stability, findings from the phase II ReSponD trial show.

Patients taking the acetylcholinesterase were much steadier during an 18 metre walking task than were patients taking placebo, demonstrating a significant 28% greater reduction in step time variability 32 weeks after starting treatment.

“We already know that rivastigmine works to treat dementia by preventing the breakdown of acetylcholine, however, our study shows for the first time that it can also improve regularity of walking, speed, and balance”, lead researcher Emily Henderson (School for Social and Community Medicine, University of Bristol, UK) commented in a press release.

In turn, patients taking rivastigmine were 45% less likely to fall than their peers given placebo, which Henderson said is “a real breakthrough”.

A total of 114 patients randomly assigned to receive rivastigmine or placebo were assessed. They had fallen at least once, and a median of five times, in the past year and were able to walk unaided for 18 metres. Rivastigmine was the patients’ first exposure to an acetylcholinesterase inhibitor and it was started at 3 mg/day and titrated to a target dose of 12 mg/day over 12 weeks.

At 32 weeks, the 55 patients in the rivastigmine group had an average step time variability during a normal walking task of 0.043 seconds, compared with 0.064 seconds for the placebo group.

“This gain might or might not be mediated via improved cognition, specifically improved attention to compensate for impaired gait resulting from striatal dopaminergic loss, or via a direct effect on gait”, the team reports in The Lancet Neurology.

Step time variability also differed somewhat when the patients were asked to walk while doing a simple cognitive task, with those in the rivastigmine being 21% steadier. However, there was no significant difference when the patients completed a complex cognitive task while walking.

The drug was also associated with a significant reduction in the monthly fall rate, which was an average of 1.4 for those taking rivastigmine, compared with 2.4 for those taking placebo. But there was no significant effect on episodes of gait freezing or neuropsychological outcomes such as fear of falling, anxiety or depression.

In a related comment, Caroline Moreau and colleagues, from Hôpital Roger Salengro, CHRU de Lille, France, say the long-awaited findings “provide valuable arguments in favour of high-dose rivastigmine treatment in patients with high-level gait disorders.”

They call for confirmation in a larger sample of patients and those with a range of cognitive and behavioural profiles.

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