High Frequency Pulsed Near Infrared Light: A novel approach for preventing neurodegeneration

Why Cognitive Impairment?

Almost one million Canadians suffer from cognitive impairment (Fig 1). Neurodegenerative conditions such as Dementia are common among the elderly, and worsen quality of life, costing Canadians 40 Billion Dollars every year1.

~50% of Mild Cognitive Impairment (MCI) progress into dementia, which deteriorates physical and cognitive function, as well as quality of life. Thus, early intervention is crucial to prevent further degradation of cognitive function2.

The Problem

There is currently no known cure for Alzheimer’s Disease, the most common form of dementia, and current pharmaceutical treatments have major side effects such as dysphagia and hallucinations3,4.

Over 40% of Alzheimer's pateints fail to adhere to treatment5.

Treatment Approach

Photobiomodulation (PBM), the use of LEDs emitting near-infrared light with the goal of modulation cell function, is a safe, tested, and non-invasive treatment method that can be adjusted to individuals, and has few side effects (Fig2).

The effects of higher frequency pulsed Near Infrared Light (NIR) remain unexplored in humans6, however recent papers have uncovered potential benefits in fighting the root cause of Alzheiemer's Disease.

Objectives

This project aims to explore the effectiveness of 1000Hz transcranial photobiomodulation in improving markers of cognition tied to Alzheimer's Disease in older adults.

Ultimately, any non-invasive tool that may be able to help fight or prevent neurodegeneration would have a massive benefit to quality of life in older adults accross Canada,

Methods were developed by reviewing research literature and consulting with experts at Vielight Canada, to understand proper stimulation protocols, as well as relevant testing metrics.

6 Men and 7 Women, aged 66-85 with a mean age of 73 were recruited from clients of the Queens Health Centre. 8 participants initially presented with Mild Cognitive Impairment (MCI) (MoCA Score <25), while 4 were neurotypical.

1 Participant dropped out due to travel difficulty.

Stimulation

Materials:

Vielight Neuropro2

Stimulation was done 15 times, with stimulation occurring 3 times a week, on par with PBM guidelines used by Vielight.

LEDs were placed primarily targeting the Default Mode Network (DMN). This network was chosen due to its high average controllability, as well as due to its association with Alzheimer’s Disease.

Stimulation lasted 23 minutes, with 8 minutes of alpha (10Hz) stimulation, 7 minutes spent gradually increasing frequency by 10Hz increments over 5 seconds, and 8 minutes of 1000Hz stimulation. This timeframe maintains comfort and is a similar length to established PBM protocols.

Testing (Before/After)

Materials:

MoCA Cognitive Assesement

Muse 2 EEG & Myndlift Sofware.

Hand-Dynanometer

Laptop-Cogniciti Assesement

Participants were given the Montreal Cognitive Assessment (MoCA)

A 17 minute qEEG was then performed using the Muse 2 headset while participants were seated. Electrodes were placed at Fz, F3, F4, Cz, and Pz positions to record Theta, Alpha, Beta, and High-Beta waves.

Average Dual Task walking speed was recorded by having participants walk a 19 meter course 3x without a dual task, followed by walking while performing serial subtraction.

Grip strength was measured 3 times on the dominant side and averaged.

A cognitive test was done using the Cogniciti digital brain health assessment.

Control

Different versions of the MoCA were used the before and after tests.

Tests were done at roughly the same time of day

Results

8 out of 12 participants presented with Mild Cognitive Impairment following the initial MoCA (score <25). These participants typically presented with heightened theta wave levels in parts of their Brainmap, consistent with MCI15.

The majority of participants showed improvements in markers of MCI, such as theta Beta Ratio (TBR), Low/High Alpha Ratio, as well as in results on the MoCA and Cogniciti (Fig 3).

MoCA scores increased by an average of 3 per participant (p=0.005). Of the 8 participants initially presenting with MCI, 5 normalized post stimulation, indicating an improvement in scores, especially among those with MCI (Fig 4).

Physical markers of cognitive function improved in most participants. Dual Task Cost (DTC) in gait-speed decreased by 41.5% (p= 0.007) after stimulation in all participants, and by 37.5% in participants with MCI (p=0.03), showing similar improvements regardless of initial condition (Fig 5). Grip strength increased by 12.8% across all participants (p=0.002).

Theta Beta Ratio (TBR), a key marker of MCI, showed small improvements overall only decreasing by 8.0% (p=0.34), however participants with MCI displayed a larger average decrease of 14.0% (p=0.16), meaning that participants with MCI had larger improvements overall. This has been associated with decreases in total tau in other papers (Fig 6) 16,17.

Low/High Alpha Ratios improved (decreased) by 11.5% (p=0.09) across all participants, and by 15% among participants that initially presented with MCI. Higher Low/High Alpha Ratios are associated with cortical thinning18.

Average absolute theta amplitude decreased by 16.9% (p=0.01) across all participants, while Relative theta Amplitude, which is associated with Cerebrospinal Fluid (CSF) tau levels19 decreased marginally by 5.8% (p=0.48). This change reflects a decrease in the strength of slower waves.

Cogniciti scores improved by an average of 29.77% among all participants (p=0.009), representing an increase of 13 points. Among those who initially presented with MCI, scores increased by an average of 31.5% (p=0.02), representing an average increase of 5 points, indicating similar improvements relative to pre-stimulation scores, regardless of initial results.

Qualitative data showed high participant satisfaction, and a correlating subjective improvement in memory, mood, and word retrieval.

Statistics

A 2-tailed Wilcoxon Signed Rank Test was used to calculate p-values for this trial. The test is non-parametric and paired. This test was chosen because the small sample size (n=12) of this study makes it difficult to assume normality, and it is less sensitive to outliers than a standard t-test, making it effective for this study20.

All metrics trended towards improvement, however results for TBR, Low/High Alpha Ratio, and Relative theta amplitude were not statistically significant (p>0.05). This is due to a mix of small numerical changes, and a low participant number. A larger study is necessary to determine the efficacy of 1000Hz PBM for improving these metrics.

PBM at 1000Hz may be an effective tool for improving cognitive outcomes and preventing the worsening of Mild Cognitive Impairments.

qEEG markers of cognition such as Low/High Alpha and TBR slightly improved, however less than hypothesized. They were, however accompanied with large, statistically significant improvements in Grip Strength, DTC, and Cognitive Assesements.

Changes in physical markers and cognitive assesement scores were far more pronounced than the EEG changes. Even if 1000hz PBM is capable of altering EEG signals, the difference could be due to EEG changes taking a longer timeframe to respond to physiological changes, or other factors such as signal noise or slight changes in electrode placement.

EEG metrics strongly linked in prior literature to Cerebrospinal Fluid (CSF) tau levels such as TBR and Average/Relative theta amplitude slightly decreased (improved), possibly signalling an improvement in tau-pathology, key for preventing neurodegeneration19.

DTC in gait-speed improved significantly, proving that 1000Hz PBM is an effective tool for improving DTC, which has been strongly linked to Dementia risk by Sakurai et. al.. Grip strength, another measure linked to dementia risk increased among all but 1 participant, signalling potential neuroprotective benefits21,22.

Improvements to Dual-Task-Cost were similar to other methods such as tDCS and tACS (~40%)23

tPBM at 1000Hz was more effective at increasing MoCA scores than similar studies using tPBM, increasing MoCA by a mean of 3, compared to 2.6 in other studies24.

A proof of concept Brain-Health-Index was created to help catch cognitive impairment across several domains (Fig-7).

While Photobiomodulation at 1000Hz is a promising tool to fight dementia, further research with a larger sample size is necessary to confirm results.

Measuring Tau levels via a CSF-analysis to confirm that 1000Hz PBM is effectively lowering total-tau levels would be beneficial, rather than measuring through surrogate qEEG metrics.

Cheaper tools for 1000Hz PBM could be utilized in nursing homes and hospitals, providing a tool to improve cognition while preventing neurodegeneration due to tau-oligomer buildup.

Stimulation at much higher frequencies may be an interesting method to test the OrchOR theory, which states that consciousness arises from quantum-processes in microtubules (Fig-8)29-30.

Thank you to all of the participants who were involved in this expirement, for their time and cooperation. Without you, this project would not have been possible.

I'd like to thank the Queens Health Centre in Thornton, who gave me the resources and help I needed to turn ideas into reality. i'd especially like to thank Michael, and Dr. Kogan.

Lastly, a big thanks to Nazanin Hosseinkah, PhD, from Vielight, for her expertise and advice.

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