Despite a lack of effect on memory and other cognitive tasks, as measured by ADAS-Cog-11, rotigotine improved frontal cognitive function and activities of daily living in those with Alzheimer.
Howard Fillit, MD
Recently published data suggest that rotigotine (Neupro; UCB pharma), a dopaminergic agonist, may have use in the improvement of frontal cognitive function and activities of daily living for patients with mild to moderate Alzheimer disease, in spite of not showing significant effects on memory and other cognitive tasks.
All told, the results of the randomized clinical trial—Effects of Dopaminergic Therapy in Patients with Alzheimer's Disease (DOPAD)—showed that the application of a 2-mg transdermal rotigotine patch for 1 week and a 4-mg patch for 23 weeks (n = 47) was associated with an estimated mean change in Alzheimer Disease Cooperative Study–Activities of Daily Living score of −3.32 (95% CI, −4.02 to −2.62) compared with a change of −7.24 (95% CI, −7.84 to −6.64; P
= 0.4) for placebo (n = 47). Additionally, Frontal Assessment Battery score changes were significantly favorable for rotigotine (0.48; 95% CI, 0.31 to 0.65) compared to placebo (−0.66; 95% CI, −0.80 to −0.52; P
Notably, the primary end point—the estimated mean change in Alzheimer Disease Assessment Scale–Cognitive Subscale score—was not significantly different between the groups (rotigotine: 2.92 [95% CI, 2.51–3.33]; placebo: 2.66 [95% CI, 2.31–3.01]; P
= .82). As well, there was no longitudinal change in Neuropsychiatric Inventory scores (rotigotine: 1.64 [95% CI, 1.06–2.22]; placebo: 1.26 [95% CI, 0.77–1.75]; P
The study was conducted by Giacomo Koch, MD, PhD, et al., who noted that within the framework of this clinical trial, the findings suggest that dopaminergic agonists such as rotigotine are safe in patients with mild to moderate Alzheimer disease. They wrote that in light of the limitations that accompany the available treatments—estimates suggest that between 40% and 70% of patients benefit from current treatments—more effective symptomatic agents, particularly in the earlier stages of pathology, are sorely needed.
The study was funded by the Alzheimer’s Drug Discovery Foundation (ADDF). To find out more about the data and the takeaways for the clinical community, NeurologyLive
spoke with Howard Fillit, MD, founding executive director and chief science officer, ADDF.
NeurologyLive: What should the clinical community take away from these data?
Howard Fillit, MD:
Executive dysfunction is a key symptom of Alzheimer’s, even early in the disease and in the MCI stage. There are currently no treatments specifically designed for executive dysfunction (planning, organizing, abstract reasoning, orientation, emotional control, working memory). This is the first study that explores repurposing rotigotine for executive dysfunction based on its dopaminerigic neurochemistry effects on frontal lobe function.
How important are the improvements that were observed with rotigotine to patients?
They improvements observed in this study were generally statistically significant. Patients treated with rotigotine had some practical improvements that are very important for people with Alzheimer’s. Additionally, rotigotine improved executive function, which helps patients with key cognitive tasks, such as reasoning, judgment, working memory, and orientation. It also improved their ability to complete routine daily activities like shopping, planning, and even bathing, toileting and feeding themselves, which means preserving their independence longer and reducing the burden on caregivers.
Does this dopaminergic focused approach still hold promise for Alzheimer?
Yes, absolutely. There have been previous trials of dopaminergic agents for Alzheimer’s, but this is the first trial to specifically demonstrate the effects of rotigotine, a drug whose safety profile is well known since it already approved for us for Parkinson’s disease. The ADDF has a long history of supporting trials like this that explore repurpose existing drugs as they have the potential to speed up our ability to find new treatments for Alzheimer’s.
Transcript edited for clarity
Koch G, Motta C, Bonni S, et al. Effect of Rotigotine vs Placebo on Cognitive Functions Among Patients With Mild to Moderate Alzheimer Disease: A Randomized Clinical Trial. JAMA Netw Open. 2020;3(7):e2010372. doi: 10.1001/jamanetworkopen.2020.10372.