Dopamine Agonist Showed No Notable Benefit in Alzheimer’s Patients

In patients with Alzheimer’s disease, a daily dose of dopamine agonist, rotigotine, showed no significant benefit from baseline to 24 weeks when compared with a placebo, according to a JAMA Network Open study.

But rotigotine at a relatively low dosage was safe and well-tolerated in patients with mild to moderate Alzheimer’s disease.

The Phase 2, randomized, double-blind clinical trial enrolled patients with mild to moderate Alzheimer disease in Italy between September 2017 and December 2018.Data were analyzed from July to September 2019.

The study was led by Giacomo Koch, MD, PhD, department of clinical and behavioral neurology, Santa Lucia Foundation Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), and Alessandro Martorana, MD, PhD, professor, memory clinic, department of systems medicine, University of Rome Tor Vergata.Their key initiative was to investigate whether therapy with dopaminergic agonists may affect cognitive functions in patients with Alzheimer Disease. Koch and Martorana looked at primary endpoint change, which was from baseline on the Alzheimer Disease Assessment Scale-Cognitive Subscale.

Rotigotine is a dopamine agonist that works by helping to restore the balance of a certain natural substance (dopamine) in the brain.

The secondary outcomes were measured by change in Frontal Assessment Battery, Alzheimer Disease Cooperative Study-Activities of Daily Living, and Neuropsychiatric Inventory (NPI) Scores.

Overall, rotigotine, as compared with placebo, had no significant effect on the primary endpoint.

The estimated mean change in the Alzheimer’s Disease Assessment Scale–Cognitive Subscale score was 2.92 for the rotigotine group and 2.66 for the placebo group.

But for the secondary outcomes, there were significant estimated mean changes between groups for Alzheimer’s Disease Cooperative Study–Activities of Daily Living score, at −3.32 for rotigotine and −7.24 for the placebo group.

Frontal Assessment Battery score was 0.48 for rotigotine and −0.66 for placebo. And neurophysiological analysis of electroencephalography results indicated that prefrontal cortical activity increased in rotigotine, but not in the placebo group.

These findings suggest that rotigotine may be useful for improving frontal cognitive functions and activities of daily living in patients with mild to moderate Alzheimer disease.

“We found that rotigotine improved cognitive functions highly related to the frontal lobe in patients with Alzheimer disease during 24 weeks, while these cognitive functions declined in patients treated with placebo,” Koch and Martorana said in the study.

“Moreover, rotigotine was efficacious in reducing the decline of functional impairment,” they add. “Our study showed an effect on the activities of daily living in the rotigotine group compared with the placebo group, suggesting that use of rotigotine could have a potential role in treating functional impairment starting in the early stages of the disease.”

Although adverse events were more common in the rotigotine group, with 11 patients dropping out compared with 5 in the placebo group, rotigotine did not induce any relevant behavioral side effects as revealed by NPI scores analysis.

Most notably, according to researchers, was that patients enrolled in the current study were in the early phase of Alzheimer’s disease and did not show any extrapyramidal signs, such as tremor or rigidity.

Any drug-induced movement disorders or side effects caused by rotigotine are more likely to appear in the later stages of Alzheimer's disease.