Avoid anticholinergics in Parkinson’s, say researchers, despite study findings

Use of anticholinergic drugs by patients with newly diagnosed Parkinson’s disease (PD) is not associated with cognitive decline, according to new research^[1]
, but the study authors say there may be “good reasons” why these findings contradict previous studies.

The study, led by Alison Yarnall, a research fellow at Newcastle University, used data from the ICICLE-PD study – a twin-centre, longitudinal, observational study exploring the development of dementia in Parkinson’s disease (PD).

The researchers studied the medication history of 219 patients with incident PD and 99 healthy controls to calculate each participant’s anticholinergic burden using the anticholinergic drug scale (ADS). Each drug was given a score from 0 to 3 according to its level of anticholinergic activity and these were summed at baseline and 18 months for each participant.

Comparing patients who had an ADS score of 0 at 18 months (PD-ADS; n=112) with those with an ADS score of one or more at both time points (PD+ADS; n=83), the researchers found no difference in global cognition or in assessments of attention, memory or executive function. The proportion of patients with mild cognitive impairment was also similar between the two groups, at 49.4% in PD+ADS and 45.5% in PD-ADS (P=0.35).

The data show that anticholinergic burden over 18 months could not be used to predict cognitive performance, say the researchers.

“Although our study did not confirm deleterious effects upon cognition, there may be good reasons for this,” says research team member David Burn, professor of movement disorder neurology at Newcastle University. “The duration of follow-up was shorter than previous studies. Our participants were also younger in comparison to other studies and had incident rather than prevalent disease.”

Anticholinergics are sometimes used in early PD to treat tremor. In this study, the researchers speculate that the overall low anticholinergic burden observed (mean ADS score at 18 months was 0.8) could be due to physician awareness of adverse outcomes associated with their use.

“Converging lines of evidence suggest that anticholinergic drugs — both those recognised as ‘classic’ anticholinergics as well as other less obvious drugs but with high anticholinergic activity — should be avoided as far as possible in people with Parkinson’s,” Burn adds.

Other studies have suggested that anticholinergic drugs can adversely affect cognition and might be involved in amyloid deposition. In addition, patients with PD frequently develop dementia, which is known to be mediated to a large extent by cholinergic deficiency.

In 2015, a much larger study^[2]
, involving more than 3,000 patients aged over 65 years, found a dose-response relationship between the use of anticholinergics and the risk of developing dementia and Alzheimer’s disease over a 10-year period.

Commenting on the latest study, Shelly Gray from the University of Washington in Seattle, lead author of the 2015 study, says prescribers should still be cautious in their use of anticholinergics among patients with PD.

“There are often alternatives to using anticholinergics in patients with PD,” she says. “Anticholinergics are linked with many other poor outcomes in older adults, including constipation, an increased risk for falls and delirium, so they are best avoided if possible.”