The Ongoing Search for Effective and Accessible Treatments for Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common type of dementia in elderly individuals worldwide (Wilson et al., 2012). The disease is characterized by neurodegeneration, tissue changes in the brain, (including amyloid-containing plaques and tangles of hyperphosphorylated tau protein), severe cognitive decline and in many cases, neuropsychiatric symptoms. The search for effective, safe and accessible treatments remains largely elusive. The currently approved drugs have considerable side effects, reducing compliance and some require increased medical follow-up and brain imaging, reducing the accessibility of the treatment to many.

YouTube player

Gamma Modulation as a Potential Treatment for Alzheimer’s Disease

Brain cells, also known as neurons, communicate with each other through electrical signals that produce patterns called brain waves. Of the 5 different types of brain waves, gamma waves are the fastest brain waves. They range from 30 to 100 Hez. Gamma brain waves are linked to cognitive functioning, learning, memory, and information processing.

Abnormal brain waves have been observed in humans with Alzheimer’s Disease (AD), including decreased power of Gamma waves.

In a landmark study, MIT demonstrated that 40Hz visual flashing resulted in improvements in memory and learning in a mouse model of AD. Decreased amyloid plaques and less brain atrophy were also noted. This 40Hz modulation is believed to increase non-inflammatory microglia, which work to remove the pathological amyloid plaque buildup. Additionally, 40 Hz modulation may increase the decreased levels of gamma in patients with AD.

Delivering Gamma Neuromodulation via Brain Photobiomodulation

Photobiomodulation is an innovative way to modulate gamma waves in the brain. The Vielight Neuro Gamma delivers near-infrared light (810nm) pulsed at 40Hz to modulate brain activity while delivering PBM therapy.

A key randomized, sham-controlled study demonstrated that delivery of 40Hz 810nm NIR energy on using the Vielight Neuro Gamma significantly increases the power of the higher oscillatory frequencies of gamma, alpha and beta and reduces the power of the slower frequencies of delta and theta in subjects in resting state. These changes were seen after a single session of PBM with the Neuro Gamma and were significantly different when compared to sham stimulation.[1] This study clearly demonstrated that 40 Hz pulsed PBM is able to modulate neuronal oscillations and increase the power of gamma in the brain.

In further support of the benefits of 40 Hz pulsed PBM for patients with AD, an independent study conducted by the The University of California San Francisco demonstrated that 12 weeks of at-home use of the Neuro Gamma in dementia patients produced improvements in mental acuity, increased cerebral perfusion and increased connectivity between the posterior cingulate cortex and lateral parietal nodes within the Default-Mode network [2].

The other benefits of brain photobiomodulation

While there are multiple ways to produce neuromodulation and increase levels of gamma in the brain, neuromodulation through pulsed photobiomodulation produces additional benefits not provided by other modalities, that would be of significant benefit to patients with AD.

Improved Mitochondrial Function

Photobiomodulation has been shown to improve mitochondrial function, resulting in increased ATP production. Mitochondrial dysfunction occurs very early in the pathogenesis of AD, and preventing this dysregulation via PBM may be of significant benefit for individuals with AD, as well as those at risk of developing AD.

Increased Blood Flow

PBM results in increased release of Nitric Oxide (NO). NO is a powerful neurotransmitter with multiple properties, one of which being vasodilation. This has been linked with increased oxygenation in the brain.

Improved Neuroprotection

A wide variety of evidence suggests that PBM can be utilized for neuroprotection as a pre-emptive measure to protect cells from future damage and reduce ongoing damage and promote their survival and longevity. [3,4,5,6]

Increased Neurogenesis and Synaptogenesis

Brain photobiomodulation has been shown to promote both synaptogenesis and neurogenesis, as evidenced through increased levels of brain derive neurotrophic factor (BDNF). [7,8]

Conclusion

Neuromodulation to increase gamma oscillations in the brain appears to produce significant clinical benefits for AD. While such neuromodulation may be achieved in more than one way, 40Hz neuromodulation via PBM has been shown to produce additional cellular benefits that are of particular relevance to patients with AD.

References

[1] Zomorrodi, Reza & Loheswaran, Genane & Pushparaj, Abhiram & Lim, Lew. (2019). Pulsed Near Infrared Transcranial and Intranasal Photobiomodulation Significantly Modulates Neural Oscillations: a pilot exploratory study. Scientific Reports. 9. 10.1038/s41598-019-42693-x.

[2] Chao LL. Effects of Home Photobiomodulation Treatments on Cognitive and Behavioral Function, Cerebral Perfusion, and Resting-State Functional Connectivity in Patients with Dementia: A Pilot Trial. Photobiomodul Photomed Laser Surg. 2019 Mar;37(3):133-141. doi: 10.1089/photob.2018.4555. Epub 2019 Feb 13. PMID: 31050950.

[3] Liang J, Liu L, Xing D. Photobiomodulation by low-power laser irradiation attenuates Abeta-induced cell apoptosis through the Akt/GSK3beta/beta-catenin pathway. Free Radic Biol Med. 2012;53:1459–1467. [PubMed] [Google Scholar][4] Eells JT, Henry MM, Summerfelt P, Wong-Riley MT, Buchmann EV, Kane M, Whelan NT, Whelan HT. Therapeutic photobiomodulation for methanol-induced retinal toxicity. Proc Natl Acad Sci U S A. 2003;100:3439–3444

[5] Wong-Riley MT, Liang HL, Eells JT, Chance B, Henry MM, Buchmann E, Kane M, Whelan HT. Photobiomodulation directly benefits primary neurons functionally inactivated by toxins: role of cytochrome c oxidase

[6] Huang YY, Nagata K, Tedford CE, Hamblin MR. Low-level laser therapy (810 nm) protects primary cortical neurons against excitotoxicity in vitro. J Biophotonics. 2014;7:656–664. [PMC free article] [PubMed] [Google Scholar][7] Meng C, He Z, Xing D. Low-level laser therapy rescues dendrite atrophy via upregulating BDNF expression: implications for Alzheimer’s disease. J Neurosci. 2013;33:13505–13517. [PMC free article] [PubMed] [Google Scholar][8] YYW Huang Q, Xuan W, Ando T, Xu T, Sharma SK, Kharkwal GB, Hamblin MR. Low Level Light Therapy for Traumatic Brain Injury [Google Scholar]