Glutamatergic Modulator Improved Cognition in Alzheimer Disease

In a small study (NCT04602624), a positive allosteric modulator of glutamatergic N-methyl D aspartate channels (SAGE-718; Sage Therapeutics, Cambridge, MA) improved cognition in people with mild cognitive impairment (MCI) and mild dementia associated with Alzheimer disease (AD). 

In this open-label study, participants’ (n=26, mean age 67) scores on the Montreal Cognitive Assessment (MoCA) improved by an average of 2.3 points, to 22.8 points. Some participants also had improvement in activities of daily living, especially complex activities (eg, using a computer, carrying out household chores, and managing their medications.) Cognitive domains were also tested with a battery of neuropyschologic tests, and consistent improvement in executive functioning, which is required for planning and decision-making as well as learning and memory were observed. 

“Cognitive impairment is often one of the earliest signs of AD, can be very difficult for patients and their families, and represents an area of great unmet medical need.” said Aaron Koenig, MD, vice president, Sage Therapeutics. “For families and patients with mild cognitive impairment, there is nothing mild about it. With an aging population and the potential for more people being afflicted by these diseases, we need to address how to minimize or even improve cognitive deficits to improve the overall course of the disease.”.” 

No treatment-emergent serious adverse events occurred; mild or moderate treatment-emergent adverse events were headache and constipation, in 5 participants.

Cognitive benefits of SAGE-718 have also been observed in clinical trials for people with Parkinson disease and Huntington disease for which studies are also ongoing.

The study is being presented at the American Academy of Neurology 74th Annual Meeting held in-person in Seattle, WA, April 2 to 7, 2022; and virtually, April 24 to 26, 2022.