Gamma Wave Sensory Stimulation May Slow Alzheimer Disease Progression and Preserve Brain Structure

Daily at-home sensory gamma stimulation treatment with the Spectris device (Cognito Therapeutics, Cambridge, MA) may help preserve brain structure and slow cognitive decline in people with Alzheimer disease (AD). In findings from the OVERTURE clinical trial (NCT03556280), presented at the 2025 meeting of the Alzheimer’s Association International Conference (AAIC), treatment was associated with both reduced white matter and myelin loss, as well as significant delays in progression of clinical symptoms of AD. Spectris is a noninvasive, at-home device designed to provide synchronized light and sound sensory stimulation to generate gamma wave oscillations.

OVERTURE is a single-blind, multicenter clinical trial in which 53 people with prodromal AD, AD, or mild cognitive impairment (MCI) due to AD were randomized 2:1 to complete treatment with either Spectris 40 Hz stimulation (n=33) or sham (n=20). The 6-month clinical trial was followed by an 18-month open-label extension (OLE) study. In one analysis, researchers estimated the clinical “time saved” in disease progression associated with Spectrim stimulation vs sham based on Alzheimer’s Disease Cooperative Study—Activities of Daily Living (ADCS-ADL) and Mini-Mental State Examination (MMSE) scores and Whole Brain Volume (WBV) measures.

Results in time saved for people treated with Spectris vs sham are as follows:

• ADCS-ADL: 4.83 months (P=.0006) in OVERTURE; 8.66 months over 14.64 months in the OLE (P<.0001)
• MMSE: 4.56 months (P=.1276) in OVERTURE; 9.93 months over 15.91 months in the OLE (P<.0001)
• WBV: 4.09 months (P=.0021) in OVERTURE; 7.48 months over 13.46 months in the OLE (P<.0001)

In another analysis, MRI data were evaluated to compare changes in white matter and corpus callosum volumes and myelination. Compared with sham treatment, Spectris stimulation was associated with a reduction in total and regional white matter atrophy and myelin content loss, especially in the entorhinal region and corpus callosum.

Additionally, based on the “What Matters Most” framework, 12 of 41 (29%) outcomes selected as being most important for patients and caregivers showed significant improvements in those receiving Spectris stimulation vs those receiving sham.

“We’re now seeing consistent outcomes with Spectris across clinical, imaging, and patient-centered domains,” said Ralph Kern, MD, MHSc, Chief Medical Officer at Cognito Therapeutics. “These findings deepen our understanding of Spectris’ neuroprotective mechanisms and further support our path toward regulatory engagement.”