Alzheimers Disease (AD) is a multifactorial, progressive neurodegenerative disease that disrupts cognitive function through maladaptive misfolded proteins, abnormal neuroimmune responses, and disordered neuronal network activities. Despite continued scientific advances in the understanding of AD biology, there remains an unmet need for safe and effective disease-modifying treatments. Sensory stimulation is an emerging therapeutic approach which has demonstrated disease-modifying effects in preclinical transgenic models of AD. This randomized, sham-controlled, clinical trial (OVERTURE; NCT03556280) evaluated the feasibility and safety of 40Hz auditory and visual stimulation with the CogTx-001 medical device in 70 participants with mild to moderate AD, administered as daily, 1-hour active stimulation (as compared to sham stimulation) over a 6-month period. Primary endpoints of the therapy showed that it was well-tolerated, showed high adherence and demonstrated a favorable safety profile. Secondary outcomes included exploratory outcomes measures such as ADCS-ADL and MMSE scores, which demonstrated significant effects on functional and cognitive abilities. Additionally, sensory stimulation also showed a significant reduction in brain volume loss and cortical thinning, without changes in amyloid PET signal in active versus sham groups. These encouraging results justify further development of 40Hz sensory stimulation as a safe and potentially disease-modifying therapy for AD patients.

M.H., A.B., E.H., M.S., A.K., C.V.S., V.F., K.K., B.V., Z.M., J.T.M. are employees of Cognito Therapeutics. J.N-J., S.H. are employees of Pentara who are contracted by Cognito Therapeutics for their service.

NCT03556280

This study was funded by Cognito Therapeutics

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was conducted in accordance with the Declaration of Helsinki and had central ethics committee reviewed and approved by Advarra Institutional Review Board at each participating site and ethics approval was given. Advarra is an Institutional Review Board Organization; IORG Number is 0000635 and Institutional Review Board Registration number is 00000971. The Clinical Investigational Plan and Study Protocol were developed in accordance with the requirements set forth in the United States Code of Federal Regulation, 21 CFR 812 Investigational Device Exemptions, ISO 14155:2011 Clinical Investigations of Medical Devices for Human Subjects, the Medical Device Directive 93/42/EEC of the European Union, and the Declaration of Helsinki by the World Health Organization (as amended in 2008). All participants provided written informed consent that adhered to all necessary policies.

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The data that support the findings of this study are available on request from the corresponding author [M.H.]. The data are not publicly available due to them containing information that could compromise research participant privacy/consent.