In 2015, our dementia pilot trial made history by being the first to show efficacy of brain photobiomodulation (PBM) for dementia in humans with a home-use device.^[1]

In 2019, Dr. Linda Chao, a professor in the Departments of Radiology, Biomedical Imaging and Psychiatry at the University of California, verified our 2015 dementia pilot trial with her own independent brain photobiomodulation study with the Vielight Neuro Gamma on participants with dementia.^[2]

Eight participants diagnosed with dementia were randomized to 12 weeks of usual care or home photobiomodulation(PBM) treatments. The PBM treatments were administered at home with the Vielight Neuro Gamma, a brain photobiomodulation device that emits 100 mW/cm² of power density at 810nm and 40hz.

Several types of assessments were used:

• Alzheimer’s Disease Assessment Scale-cognitive subscale and the Neuropsychiatric Inventory at baseline and 6 and 12 weeks
• Magnetic resonance imaging (MRI) and resting-state functional MRI at baseline and 12 weeks.

Results:

Figure 1. ADAS-cog (A) and NPI-FS (B) scores in the PBM (blue line) and UC (red line) groups by time. Lower scores on both measures indicate better function.

After 12 weeks, there were improvements in ADAS-cog and in the NPI.

A summary measure of the individual domain scores: higher NPI-FS scores reflect more severe/more frequent dementia-related behavior.

In this study, the PBM group improved an average of -12.3 points on the NPI-FS after 6 weeks and -22.8 points after 12 weeks of treatments.

By comparison, previous pharmacological trials of donepezil reported no difference from placebo on behavioral symptoms measured by the NPI and no difference on quality of life.^[3]

Importantly, there were no adverse effects associated with the PBM treatments in this or Saltmarche et al.’s study. In contrast, many of the Food and Drug Administration approved pharmacological treatments for dementia have been associated with substantial side effect burden, such as diarrhea, vomiting, nausea, and fatigue.

Figure 2 Increased cerebral perfusion with the Vielight Neuro Gamma

The third finding of this study is that cerebral perfusion (CBF) increased after 12 weeks in the PBM group compared to the UC group. This finding is consistent
with previous reports of PBM-related increases in local CBF, oxygen consumption, total hemoglobin, a proxy for increased rCBF, rCBF, and increased oxygenated/decreased deoxygenated hemoglobin concentrations.

Interestingly, the PBM-related increases in perfusion were most prominent in the parietal ROIs. This may relate to the fact that the Vielight Neuro Gamma used in this study had three transcranial LED clusters over the parietal lobe and only one transcranial LED cluster over the frontal lobe. This finding may also be explained by the report that NIR light penetrates more deeply through the parietal lobe compared to the frontal lobe due to the higher power density of the rear transcranial LED modules .

Connectivity changes in the DMN have been described in populations at risk for AD as well as in patients with AD. Because decreased DMN connectivity is a common finding in resting-state connectivity studies of AD,^[4] it is significant that there was increased functional connectivity between the PCC and the LP nodes of the DMN in the PBM group after 12 weeks compared to the UC group.

There have been reports of increased functional connectivity in the DMN after pharmacological treatments in mild-to-moderate AD patients.^[5-9] There have also been studies that reported changes in functional connectivity after nonpharmacological intervention in patients with MCI.^[10-12] To our knowledge, this is the first report of functional connectivity changes in dementia patients after a nonpharmacological intervention.

References

[1] Saltmarche AE, Naeser MA, Ho KF, Hamblin MR, Lim L. Significant Improvement in Cognition in Mild to Moderately Severe Dementia Cases Treated with Transcranial Plus Intranasal Photobiomodulation: Case Series Report. Photomed Laser Surg. 2017 Aug;35(8):432-441. doi: 10.1089/pho.2016.4227. Epub 2017 Feb 10. PMID: 28186867; PMCID: PMC5568598.

[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] Birks JS, Harvey RJ. Donepezil for dementia due to Alzheimer’s disease. Cochrane Database Syst Rev 2018;6:CD001190

[4] Vemuri P, Jones DT, Jack CR, Jr. Resting state functional MRI in Alzheimer’s Disease. Alzheimers Res Ther 2012;4:2

[5] Sole-Padulles C, Bartres-Faz D, Llado A, et al. Donepezil treatment stabilizes functional connectivity during resting state and brain activity during memory encoding in Alzheimer’s disease. J Clin Psychopharmacol 2013;33:199–205.

[6] Goveas JS, Xie C, Ward BD, Wu Z, Li W, Franczak M. Recovery of hippocampal network connectivity correlates with cognitive improvement in mild Alzheimer’s disease patients treated with donepezil assessed by resting-state fMRi. J Magn Reson Imaging 2011;34:764–773.

[7] Li W, Antuono PG, Xie C, et al. Changes in regional cerebral blood flow and functional connectivity in the cholinergic pathway associated with cognitive performance in subjects with mild Alzheimer’s disease after 12-week donepezil treatment. Neuroimage 2012;60:1083–1091.

[8] Blautzik J, Keeser D, Paolini M, et al. Functional connectivity increase in the default-mode network of patients with Alzheimer’s disease after long-term treatment with galantamine. Eur Neuropsychopharmacol 2016;26:602–613.

[9] Lorenzi M, Beltramello A, Mercuri NB, et al. Effect of memantine on resting state default mode network activity in Alzheimer’s disease. Drugs Aging 2011;28:205–217

[10] Chirles TJ, Reiter K, Weiss LR, Alfini AJ, Nielson KA, Smith JC. Exercise training and functional connectivity changes in mild cognitive impairment and healthy elders. J Alzheimers Dis 2017;57:845–856.

[11] Suo C, Singh MF, Gates N, et al. Therapeutically relevant structural and functional mechanisms triggered by physical and cognitive exercise. Mol Psychiatry 2016;21:1645.

[12] Wells RE, Kerr CE, Wolkin J, et al. Meditation for adults with mild cognitive impairment: a pilot randomized trial. J Am Geriatr Soc 2013;61:642–645.