A feasibility trial of gamma sensory flicker for patients with prodromal Alzheimer's disease

He, Qiliang; Colon-Motas, Kay M; Pybus, Alyssa F.; Piendel, Lydia A; Seppa, Jonna K; Walker, Margaret L.; Manzanares, Cecelia; Qiu, Deqiang; Miocinovic, Svjetlana; Wood, Levi B.; Levey, Aĺlan I.; Lah, James J.; Singer, Annabelle C.

doi:10.1002/trc2.12178

Cited by 70 publications

(86 citation statements)

References 31 publications

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“…The present findings demonstrate that of 40 Hz audiovisual stimulation, eliciting 40 Hz gamma oscillation improves sleep quality and maintains functional abilities in mild to moderate AD patients and confirm a positive safety profile of the treatment with high patient adherence. The current findings are in line with a recent publication reporting that 4-or 8-weeks gamma sensory stimulation therapy is safe, tolerable, and feasible in subjects with mild cognitive impairment due to AD (He et al, 2021).…”

Section: Discussionsupporting

confidence: 92%

Sensory-Evoked 40-Hz Gamma Oscillation Improves Sleep and Daily Living Activities in Alzheimer’s Disease Patients

Cimenser¹,

Hempel²,

Travers³

et al. 2021

Front. Syst. Neurosci.

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Pathological proteins contributing to Alzheimer’s disease (AD) are known to disrupt normal neuronal functions in the brain, leading to unbalanced neuronal excitatory-inhibitory tone, distorted neuronal synchrony, and network oscillations. However, it has been proposed that abnormalities in neuronal activity directly contribute to the pathogenesis of the disease, and in fact it has been demonstrated that induction of synchronized 40 Hz gamma oscillation of neuronal networks by sensory stimulation reverses AD-related pathological markers in transgenic mice carrying AD-related human pathological genes. Based on these findings, the current study evaluated whether non-invasive sensory stimulation inducing cortical 40 Hz gamma oscillation is clinically beneficial for AD patients. Patients with mild to moderate AD (n = 22) were randomized to active treatment group (n = 14; gamma sensory stimulation therapy) or to sham group (n = 8). Participants in the active treatment group received precisely timed, 40 Hz visual and auditory stimulations during eye-closed condition to induce cortical 40 Hz steady-state oscillations in 1-h daily sessions over a 6-month period. Participants in the sham group were exposed to similar sensory stimulation designed to not evoke cortical 40 Hz steady-state oscillations that are observed in the active treatment patients. During the trial, nighttime activities of the patients were monitored with continuous actigraphy recordings, and their functional abilities were measured by Alzheimer’s Disease Cooperative Study – Activities of Daily Living (ADCS-ADL) scale. Results of this study demonstrated that 1-h daily therapy was well tolerated throughout the 6-month treatment period by all subjects. Patients receiving gamma sensory stimulation showed significantly reduced nighttime active periods, in contrast, to deterioration in sleep quality in sham group patients. Patients in the sham group also showed the expected, significant decline in ADCS-ADL scores, whereas patients in the gamma sensory stimulation group fully maintained their functional abilities over the 6-month period. These findings confirm the safe application of 40 Hz sensory stimulation in AD patients and demonstrate a high adherence to daily treatment. Furthermore, this is the first time that beneficial clinical effects of the therapy are reported, justifying expanded and longer trials to explore additional clinical benefits and disease-modifying properties of gamma sensory stimulation therapy.Clinical Trial Registration:clinicaltrials.gov, identifier: NCT03556280.

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Section: Discussionsupporting

confidence: 92%

Sensory-Evoked 40-Hz Gamma Oscillation Improves Sleep and Daily Living Activities in Alzheimer’s Disease Patients

Cimenser¹,

Hempel²,

Travers³

et al. 2021

Front. Syst. Neurosci.

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“…Current studies demonstrated that short time exposure to light flicker stimulation was safe and tolerable by the test subjects. A longer-term treatment for 4 to 8 weeks at 1 h per day was also reported to be safe and tolerable by human test subjects ( He et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, microstate analysis identified significantly altered microstate coverage, duration, transitioning, and LZC. Almost all of these parameters have been reported in the literature to be changed in diseased brains such as AD, schizophrenia, and stroke ( Mecarelli et al, 2011 ; Nishida et al, 2013 ; Liu et al, 2016 ; Milz et al, 2017 ; Zappasodi et al, 2017 ; Musaeus et al, 2019 , 2020 ; Smailovic and Jelic, 2019 ; Briels et al, 2020 ; da Cruz et al, 2020 ; Sebastián-Romagosa et al, 2020 ; Tait et al, 2020 ; He et al, 2021 ; Klepl et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, more evidence is emerging showing that light flicker entrainment in the brain affects a wide range of physiological processes, including circadian rhythms and sleep ( Yao et al, 2020a , b ). As such, the feasibility of using 40 Hz light flicker to treat human neurological diseases is actively explored and debated ( Duecker et al, 2021 ; He et al, 2021 ). The main aim of the present study was to determine the effect of 40 Hz light flicker visual stimulation in healthy human brains using multichannel (64 channels) electroencephalography (EEG).…”

Section: Introductionmentioning

confidence: 99%

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40 Hz Light Flicker Alters Human Brain Electroencephalography Microstates and Complexity Implicated in Brain Diseases

Zhang

Luo

et al. 2021

Front. Neurosci.

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Previous studies showed that entrainment of light flicker at low gamma frequencies provided neuroprotection in mouse models of Alzheimer’s disease (AD) and stroke. The current study was set to explore the feasibility of using 40 Hz light flicker for human brain stimulation for future development as a tool for brain disease treatment. The effect of 40 Hz low gamma frequency light on a cohort of healthy human brains was examined using 64 channel electroencephalography (EEG), followed by microstate analyses. A random frequency light flicker was used as a negative control treatment. Light flicker at 40 Hz significantly increased the corresponding band power in the O1, Oz, and O3 electrodes covering the occipital areas of both sides of the brain, indicating potent entrainment with 40 Hz light flicker in the visual cortex area. Importantly, the 40 Hz light flicker significantly altered microstate coverage, transition duration, and the Lempel-Ziv complexity (LZC) compared to the rest state. Microstate metrics are known to change in the brains of Alzheimer’s disease, schizophrenia, and stroke patients. The current study laid the foundation for the future development of 40 Hz light flicker as therapeutics for brain diseases.

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“…Additionally, the active group showed less brain atrophy and more importantly did not show further hippocampal atrophy or ventricular expansion in relation to the control group, indicating a possible delay in the disease progression. In the same manner, He et al (2021) recruited 10 patients with prodromal AD who received daily 40 Hz audiovisual sensory stimulation for 1 h over the course of 4 or 8 weeks. Even though, control group or sham stimuli were not included for comparison reasons, the study indicated that the treatment was safe and resulted in improved functional connectivity in the default mode network and altered cytokines and immune factors in the cerebrospinal fluid.…”

Section: Sensory Gamma Frequency Stimulation In Alzheimer’s Disease Patientsmentioning

confidence: 99%

Gamma Oscillations in Alzheimer’s Disease and Their Potential Therapeutic Role

Traikapi

Konstantinou

2021

Front. Syst. Neurosci.

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Despite decades of research, Alzheimer’s Disease (AD) remains a lethal neurodegenerative disorder for which there are no effective treatments. This review examines the latest evidence of a novel and newly introduced perspective, which focuses on the restoration of gamma oscillations and investigates their potential role in the treatment of AD. Gamma brain activity (∼25–100 Hz) has been well-known for its role in cognitive function, including memory, and it is fundamental for healthy brain activity and intra-brain communication. Aberrant gamma oscillations have been observed in both mice AD models and human AD patients. A recent line of work demonstrated that gamma entrainment, through auditory and visual sensory stimulation, can effectively attenuate AD pathology and improve cognitive function in mice models of the disease. The first evidence from AD patients indicate that gamma entrainment therapy can reduce loss of functional connectivity and brain atrophy, improve cognitive function, and ameliorate several pathological markers of the disease. Even though research is still in its infancy, evidence suggests that gamma-based therapy may have a disease-modifying effect and has signified a new and promising era in AD research.

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A feasibility trial of gamma sensory flicker for patients with prodromal Alzheimer's disease

Cited by 70 publications

References 31 publications

Sensory-Evoked 40-Hz Gamma Oscillation Improves Sleep and Daily Living Activities in Alzheimer’s Disease Patients

Sensory-Evoked 40-Hz Gamma Oscillation Improves Sleep and Daily Living Activities in Alzheimer’s Disease Patients

40 Hz Light Flicker Alters Human Brain Electroencephalography Microstates and Complexity Implicated in Brain Diseases

Gamma Oscillations in Alzheimer’s Disease and Their Potential Therapeutic Role

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