Rivastigmine May Improve Executive Function in Parkinson's Dementia

Allison Gandey

October 21, 2009

October 21, 2009 (Baltimore, Maryland) — Results from a post hoc analysis of data from a randomized placebo-controlled trial suggest that rivastigmine (Exelon, Novartis) eases symptoms in patients with Parkinson's dementia. Presenting here at the 134th annual meeting of the American Neurological Association, investigators showed the cholinesterase inhibitor may improve executive function.

Researchers say rivastigmine, first approved in the United States for Alzheimer's disease, and more recently for Parkinson's dementia, is benefiting patients.

It was a message that attendees might have been hard pressed to miss at the meeting, with multiple post hoc and retrospective analyses to this effect presented during the poster session. Investigators were the first to admit the limitations of what they called "mostly hypothesis-generating" studies.

"These data are derived from the original 24-week trial of rivastigmine," Martin Farlow, MD, from Indiana University at Indianapolis, told Medscape Neurology about 2 of his posters. "It was that pivotal study that first got rivastigmine approved in Parkinson's in the United States and Europe." The Exelon in Parkinson's disease dementia study, known as EXPRESS, included 541 patients from multiple centers.

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Dr. Martin Farlow outlines the adverse event profile of rivastigmine.

The new analysis, also led by Frederick Schmitt, PhD, from the Sanders-Brown Center on Aging in Lexington, Kentucky, evaluated secondary outcome measures from the trial and assessed executive function. The investigators used Delis-Kaplan Executive Function System (D-KEFS) subtests and the Symbol Digit Modalities test. Patients had Parkinson's for 2 or more years and were experiencing mild to moderate dementia.

Researchers report the numbers for this analysis were small because executive-function tests were not performed at all sites.

Number of Patients Who Provided Data on Executive Function

Test Rivastigmine 3 – 12 mg per day Placebo
D-KEFS letter fluency 258 144
D-KEFS card sorting 49 22
D-KEFS color-word 62 35
Symbol digit modalities 43 22

The results presented on the poster depict a series of figures outlining a benefit of rivastigmine, but the authors did not provide a clear numerical breakdown for the D-KEFS letter fluency, card sorting, or symbol digit modalities tests.

In the D-KEFS color-word interference test, the authors report that treatment with rivastigmine resulted in fewer self-corrected errors vs placebo (n = 29 and −0.6 points vs n = 11 and 1.1 points). The researchers report no significant treatment differences for the naming, reading, and inhibition tasks.

"The medication is helpful," Dr. Farlow said during an interview. "The effects clearly aren't just with memory and general functioning but are improving other areas as well, such as tasks that require multiple steps."

Dr. Farlow suggested that as many as 70% of Parkinson's patients will develop dementia at some point during the course of their illness. "This is one study that demonstrates a beneficial effect of treating cognitive symptoms," he said.

One study, but with so many post hoc analyses presented at the meeting, it might have been easy to forget that all of the data were based on a single clinical trial.

Dr. Quincy Almeida

Asked by Medscape Neurology to comment, Quincy Almeida, PhD, from Wilfrid Laurier University in Waterloo, Ontario, Canada, said, "We have many patients that are being prescribed rivastigmine, and so the results of the study are promising."

He added, "It would have been nice to see significant improvements on more subtests of DKEFS, and it is also important to consider how Parkinson motor deficits might have an overall influence on speed tests." For example, he noted, bradyphrenia can often be confused with slow speech initiation and production. "It certainly appears to be worthy of further investigation."

This study was supported by Novartis Pharmaceuticals. Senior author Jason Olin is a Novartis employee, and he coauthored the other rivastigmine posters at the meeting.

American Neurological Association 134th Annual Meeting: Poster T66. Presented October 13, 2009.


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