Harnessing Gamma Frequencies to Modulate Alzheimer Pathology: Ralph Kern, MD, MHSc

WATCH TIME: 10 minutes

"We’re starting a new trend where we’re saying white matter is important, myelin is important, and treatments that impact that deserve serious attention. For too long, these areas have been overlooked in Alzheimer’s research, and we believe that’s beginning to change."

The therapeutic landscape for Alzheimer disease (AD) is constantly evolving, with new targets, modalities, and avenues being introduced each year. While monoclonal antibodies focused on removing amyloid plaques have shown promise, most researchers in the field believe AD will truly be treated with a combination of therapeutics. One agent in development, Cognito Therapeutics’ Spectris device, has shown promise as a potential treatment, with phase 2 findings demonstrating lower rates of brain atrophy and significantly slowing of AD progression vs placebo.

The novel therapy, set to enter a phase 3 study, is designed to evoke gamma wave activity through noninvasive visual and auditory stimulation. During the 2025 AD/PD International Conference on Alzheimer’s and Parkinson’s Diseases, held April 1-5 in Vienna, Austria, Cognito presented a few posters related to its efficacy, using participants from the previously conducted phase 2 OVERTURE study (NCT03556280). In one such poster, findings showed that participants from that study treated with Spectris had more preserved total area of corpus callosum (CC) over a 6-month period as compared with matched participants from the Alzheimer’s Disease Neuroimaging Initiative (percentage change in active vs sham: 2.28 [±0.87]; P <.02).^1,2

To better understand these findings, as well as Spectris’ impacts on subregions of CC, NeurologyLive^® sat down with Ralph Kern, MD, MHSc, chief medical officer at Cognito. In the interview, Kern gave an overview of how the stimulation device operates and the science behind it, its clinical advantages, and some of the biological and neuroimaging data observed to date. In addition, he spoke on the comparative analysis and how it underscores white matter preservation in treated patients, particularly in the CC–a structure gaining traction as a biomarker for treatment response. He also gave clinical insights on the anticipated phase 3 HOPE study as enrollment enters its final stages.

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REFERENCES
1. Kern R, Lee L, Cimenser A, Hajos M, Bendlin BB. SPECTRIS™ TREATMENT PRESERVES CORPUS CALLOSUM STRUCTURE IN ALZHEIMER'S DISEASE: A COMPARATIVE STUDY. Presented at: 2025 AD/PD conference; April 1-5. ABSTRACT 2054
2. Hajos M, Jackson BL, Hernandez M, Rowe O, Seshagiri C, Kern R. SENSORY EVOKED GAMMA OSCILLATION CORRELATES WITH BRAIN MORPHOLOGY IN ALZHEIMER’S DISEAE. Presented at: 2025 AD/PD conference; April 1-5. ABSTRACT 2000.