Ultra-high-frequency visual stimulation as potential treatment for Alzheimer’s Disease

AD impairs long-term memory. Disease-modifying drugs targeting the AD neuropathology eliminate amyloid-beta from the brain, but their effect on memory is only moderate [1]. We propose an intervention [2] focused on Sharp-Wave-Ripples (SWRs): SWR density correlates with memory [3] and inducing SWRs can improve memory [4]. Ultra-high-frequency visual (UHV) stimulation offers a safe and non-invasive way to induce SWRs [5]. It could represent a therapy for memory impairment, preventing or delaying the onset of AD or cognitive decline due to aging. NIN-AD (DRKS00036848, double blind RCT) evaluates adherence and tolerability of UHV stimulation, its effects on AD symptoms and biomarkers, memory, sleep, general wellbeing, and daily functioning.

The 3 months readout indicates high adherence to 1h/day self-administered stimulation. Participants report no side effects of the UHV stimulation, supporting safety of the intervention. Subjective memory assessment is significantly improved in the UHV group compared to a decline in the sham group. Neuropsychological tests and caregiver-assessment of daily living activities indicate positive trends between groups. Bi-weekly verbal memory tests indicate improved memory in the UHV group. Success of the full trial could promise safe and accessible therapies of AD, MCI, and age-related memory loss.

1. van Dyck, C. H. et al. Lecanemab in Early Alzheimer’s Disease. N Engl J Med 388, 9–21 (2023).

2. Keil, J. et al. Artificial sharp-wave-ripples to support memory and counter neurodegeneration. Brain Research 148646 (2023).

3. Norman, Y. et al. Hippocampal sharp-wave ripples linked to visual episodic recollection in humans. Science 365, eaax1030 (2019).

4. Fernández-Ruiz, A. et al. Long-duration hippocampal sharp wave ripples improve memory. Science 364, 1082–1086 (2019).

5. Keil, J. et al. High-frequency visual stimulation can increase medial temporal lobe ripple oscillation density. Preprint at https://doi.org/10.31234/osf.io/5c7fb_v1 (2025).