Noninvasive Terahertz Wave Binocular Stimulation Improves Cognition in Amyloid-β-Related Dementia

Terahertz (THz) waves occupy a unique spectral region where they can resonantly interact with collective vibrational modes of biomolecules, thereby modulating protein conformation and subsequently affecting neural signaling. However, whether noninvasive THz wave stimulation can be extended to Alzheimer's disease and related dementias (ADRD) remains unknown. Here, we demonstrate that 14 d of noninvasive THz wave binocular stimulation (33 THz) effectively restores cognitive performance and neural homeostasis in Aβ_1-42-induced dementia mice, a widely used experimental model of ADRD with the features including neuroinflammation and cognitive decline. Behavioral assessments revealed a marked restoration of spatial learning and memory ability, with a 53.1% ± 22.0% improvement compared with untreated dementia mice. Furthermore, THz wave stimulation reduced sleep fragmentation and restored physiological sleep-wake dynamics, indicating improved neural homeostasis. In the hippocampus, binocular stimulation attenuated microglial activation and normalized the levels of pro-inflammatory cytokines including interleukin-1β and tumor necrosis factor-α. Concurrently, THz wave stimulation activated hippocampal cyclic adenosine monophosphate (cAMP)-cAMP-response element binding protein (CREB)-brain-derived neurotrophic factor (BDNF) signaling, promoting neurotrophic support and re-establishing cholinergic functional integrity. Our findings demonstrate that THz wave binocular stimulation is a noninvasive approach capable of improving cognitive function in a dementia mouse model, offering a potential strategy to restore brain function in neurodegenerative diseases.