Rotigotine May Improve Frontal Lobe Function in Alzheimer Patients

By Reuters Staff

July 22, 2020

NEW YORK (Reuters Health) - Rotigotine did not improve overall cognitive performance in mild to moderate Alzheimer disease (AD) in a phase II trial, but patients on the drug showed "clear and remarkable" improvements in frontal lobe-related function.

Study participants taking the drug also had greater improvement in activities of daily living (ADL), Dr. Giacomo Koch of IRCCS Fondazione S. Lucia in Rome and colleagues found.

The drug is presently used to treat Parkinson's disease and restless legs syndrome.

"We chose to evaluate the effects of rotigotine on frontal lobe functions because dopamine largely modulates frontal cortex activity, and a previous study showed that treatment with rotigotine induces an improvement of cortical plasticity in the frontal cortex in patients with mild Alzheimer disease," Dr. Koch and his team explain in their report in JAMA Network Open.

They randomized 94 patients with mild to moderate AD who were already taking acetylcholinesterase inhibitors to receive rotigotine via transdermal patch, one week at 2 mg/day followed by 23 weeks at 4 mg/day, or a placebo patch for 24 weeks.

There were no differences between the rotigotine and placebo groups in week 24 cognitive performance based on the Alzheimer Disease Assessment Scale-Cognitive Subscale, with a mean change of 2.92 and 2.66, respectively. However, there were significant differences between the groups in Alzheimer Disease Cooperative Study-Activities of Daily Living scores, which declined by 3.32 points in the rotigotine group versus 7.24 points in the placebo group. Frontal Assessment Battery scores increased by 0.48 points from baseline with rotigotine, versus a decline of 0.66 in the placebo group. Neuropsychiatric Inventory total score changes were similar for the rotigotine and placebo groups.

In a subset of 40 patients who underwent electroencephalography, those on rotigotine showed increased prefrontal cortical activity, but those on placebo did not.

Eleven patients on rotigotine dropped out of the study due to adverse events, versus five patients on placebo.

"The present randomized clinical trial indicates that the use of dopaminergic agonists, such as rotigotine, is safe in patients with mild to moderate Alzheimer disease. Treatment with rotigotine may have a potential effect in reducing symptoms associated with frontal lobe cognitive dysfunction and in delaying the impairment of activities of daily living," Dr. Koch and colleagues conclude.

SOURCE: JAMA Network Open, online July 15, 2020.