40 Hz invisible spectral flicker and its potential use in Alzheimer's light therapy treatment

Abstract

Alzheimer's disease (AD) not only takes an emotional toll on the individual with the disease, their families, relatives, and caretakers, it also has immense socioeconomic consequences on the health care system and society. Moreover, the socioeconomic consequences are expected to increase significantly, thus reducing the social and economic cost of AD is of high importance. Recently, exposure to 40 Hz stroboscopic light therapy, for one hour a day, resulted in slowing the progression of AD in mice and has a considerable potential for treatment in humans. However, exposure to such stroboscopic light carries its own consequences being that it is difficult to implement in a patient's daily routine, irksome to use, and can cause visual discomfort which may result in a lack of patient adherence. Here, we demonstrate a novel technology based on controlling multiple single-color LEDs to produce white light where its spectral composition alternates at a given modulation frequency without visible flicker. We coin this technique as Invisible Spectral Flicker (ISF). We present 40 Hz invisible spectral flicker light as a potential alternative in reducing discomfort compared to 40 Hz stroboscopic light, whilst still entraining oscillations in various areas of the brain. Furthermore, we demonstrate a distinct way to generate a 40 Hz metameric light source with the presented color mixing scheme, and validate that the CIE 1931 (x, y) coordinates match for two different spectral power distributions. Finally, we illustrate the light characteristics of seven 40 Hz color fusion light sources and two 40 Hz stroboscopic light sources. The technology presented here will lead to new, and hopefully improved, designs of light therapy systems for the treatment of Alzheimer's and dementia.

Cognitive tasks propagate the neural entrainment in response to a visual 40 Hz stimulation in humans

“…If the efficacy of the therapy correlates with the strength/propagation of the entrainment, then the introduction of an additional mental task can help to shorten the currently conducted entrainment sessions in order to reach a predefined desired effect. This, together with a safe (He et al, 2021 ) and less taxing flickering stimulation procedure that is currently underway (Carstensen et al, 2020 ; Figueiro and Leggett, 2021 ), would make the non-invasive and non-pharmacological GENUS therapy more attractive and user-friendly. It is worth mentioning that the therapy if and when available with target the MCI or even earlier stages of disease considering the effect of any experimental disease-modifying therapy in the later stages of AD doomed to a failure due to irreversibility of neuronal damage in this stage.…”

Safety, Feasibility, and Potential Clinical Efficacy of 40 Hz Invisible Spectral Flicker versus Placebo in Patients with Mild-to-Moderate Alzheimer’s Disease: A Randomized, Placebo-Controlled, Double-Blinded, Pilot Study

“…r e c t e d A u t h o r P r o o fference between the placebo light and the active 40 Hz ISF[24], indicating that 40 Hz ISF is associated with similar amount of discomfort as the placebo which is analogous to bright light therapy. Participants preferred to direct their gaze to the lower part of the LTS, which is likely caused by all participants incorporating the intervention with their breakfast, thus having food and drinks between themselves and the LTS.Whether direct gaze at the device is needed for 40 Hz entrainment is unknown.…”

Study on the effect of 40 Hz non-invasive light therapy system. A protocol for a randomized, double-blinded, placebo-controlled clinical trial

“…This study will use a novel form of light called Invisible Spectral Flicker (ISF) ( Carstensen et al, 2020 ). ISF alternates between two color profiles to achieve a 40 Hz flicker which is perceived as uniformly non-flickering by the observer, as ongoing studies in our group investigate.…”