Aducanumab in Early Alzheimer's: Slowing Cognitive and Functional Decline

Ryan Quigley:
You’re listening to NeuroFrontiers on ReachMD, and this is an AudioAbstract. I’m Ryan Quigley, and today, we’re diving into the latest data from the EMERGE trial, which evaluated the treatment option aducanumab in patients with early Alzheimer’s disease.

Now, for some background, the anti-amyloid antibody aducanumab has generated quite a bit of discussion in the Alzheimer’s field, particularly around the clinical relevance of its effects. Previous reports from EMERGE showed that patients receiving high-dose aducanumab experienced significantly less progression on all prespecified endpoints at week 78 compared to placebo. But a new analysis aims to go a step further by exploring the clinical meaningfulness behind those numbers.

In terms of the study’s design, researchers applied both prespecified principal component analyses and post hoc assessments to item-level data. This enabled them to look beyond aggregate scores and instead examine individual domains and subdomains, like daily function, cognition, and behavioral symptoms.

Participants in EMERGE had early-stage Alzheimer’s disease and were stratified by APOE ε4 status. They were randomized in equal proportions to receive either a low or high dose of aducanumab, or placebo. The new analysis focused primarily on those in the high-dose group, and the results are promising.

Across all five clinical endpoints assessed, high-dose aducanumab consistently slowed disease progression. And this wasn’t limited to just cognitive testing; the benefits extended across multiple functional and behavioral measures.

And the effect didn’t plateau, either. In fact, treatment effects grew over time during the 18-month study window. That increasing separation from placebo suggests that the benefits of treatment may accumulate, which is a key consideration for a progressive disease like Alzheimer’s.

So, what do these findings mean for our patients?

According to the analysis, aducanumab helped preserve cognitive ability, prolonged the ability to perform daily tasks independently, and reduced behavioral disturbances. Together, these domains shape the clinical experience of the disease—not only for patients, but also for their caregivers and healthcare teams.

But of course, like any analysis, this has limitations. The item-level and domain-specific insights are based in part on post hoc evaluations, which are exploratory by nature. And so these findings are hypothesis-generating and require further validation in future trials or real-world data.

Still, the consistency across endpoints and the persistence of effect suggest that aducanumab’s impact may go beyond biomarker shifts and support meaningful clinical outcomes in early-stage Alzheimer’s.

This has been an AudioAbstract, and I’m Ryan Quigley. To access this and other episodes in our series, visit NeuroFrontiers on ReachMD dot com, where you can Be Part of the Knowledge. Thanks for listening!

Reference:
Cummings J, Cohen S, Murphy J, et al. Evaluation of cognitive, functional, and behavioral effects observed in EMERGE, a phase 3 trial of aducanumab in people with early Alzheimer's disease. Alzheimers Dement. 2025;21(6):e70224. doi:10.1002/alz.70224