An update on the use of gamma (multi)sensory stimulation for Alzheimer's disease treatment

Abstract

Alzheimer's disease (AD) is characterized by reduced fast brain oscillations in the gamma band (γ, > 30 Hz). Several animal studies show that inducing gamma oscillations through (multi)sensory stimulation at 40 Hz has the potential to impact AD-related cognitive decline and neuropathological processes, including amyloid plaques deposition, neurofibrillary tangles formation, and neuronal and synaptic loss. Therefore Gamma Entrainment Using Sensory stimulation (GENUS) is among the most promising approaches for AD patients' treatment. This review summarizes the evidence on GENUS effectiveness, from animal models to AD patients. Despite the application on human is in its infancy, the available findings suggest its feasibility for the treatment of AD. We discuss such results in light of parameter improvement and possible underlying mechanisms. We finally emphasize the need for further research for its development as a disease-modifying non-pharmacological intervention.

Keywords: 40 Hz stimulation; dementia; gamma waves; multi-sensory therapy; neuromodulation; non-invasive brain stimulation.

Figure 1

GENUS mechanisms on the AD-related neuropathological cascade (within the blue square). GENUS can directly affect (red arrows) gamma oscillations, excitatory/inhibitory (E/I) balance, cerebral blood flow (CBF), and morpho-functional properties of microglia. In turn, such improvements can indirectly impact (black and red arrows) brain atrophy process, amyloid-beta (Aβ) plaques, and neurofibrillary phosphorylated-tau (p-tau) tangles formation, thus cognitive and behavioral manifestations. The strongest effects derive from combining visual and auditory stimulation, rather than using a single modality.