Treatment of Neurodegeneration: Integrating Photobiomodulation and Neurofeedback in Alzheimer's Dementia and Parkinson's: A Review.

Objective: A review of photobiomodulation (PBM) in Alzheimer's dementia is submitted. The addition of PBM in neurodegenerative diseases is a dual modality that is at present gaining traction as it is safe, antiviral, and anti-inflammatory for treating neurodegeneration with photons that stimulate mitochondria increasing adenosine triphosphate and proteasomes increasing misfolded protein removal. Neurofeedback provides neural plasticity with an increase in brain-derived nerve factor mRNA and an increase in dendrite production and density in the hippocampus coupled with overall growth in dendrites, density, and neuronal survival. Background: Alzheimer's disease pathophysiology is the accumulation of hyperphosphorylated tau protein neurofibrillary tangles and subsequently amyloid-beta (Aß) plaques. PBM and neurobiofeedback (NBF)address the multiple gene expression and upregulation of multiple pathogenic pathway inflammation, reactive oxidative stress, mitochondrial disorders, insulin resistance, methylation defects, regulation of neuroprotective factors, and regional hypoperfusion of the brain. There is no human evidence to suggest a clinical therapeutic benefit from using consistent light sources while significantly increasing safety concerns. Methods: A PBM test with early- to mid-Alzheimer's was reported in 2017, consisting of a double-blind, placebo-controlled trial in a small pilot group of early- to mid-dementia subjects under Institutional Review Board (IRB)-approved Food and Drug Administration (FDA) Clinical Trial. Results: PBM-treated subjects showed that active treatment subjects tended to show greater improvement in the functioning of the executive: clock drawing, immediate recall, practical memory, and visual attention and task switching (Trails A&B). A larger study using the CerebroLite helmet in Temple Texas again of subjects in a double-blind, placebo-controlled IRB-approved FDA Clinical Trial demonstrated gain in memory and cognition by increased clock drawing. Conclusions: Next-generation trials with the Cognitolite for Parkinson's disease subjects will incorporate the insights regarding significant bilateral occipital hypocoherence deficits gained from the quantitative EEG analyses. Future applications will integrate noninvasive stimulation delivery, including full-body and transcranial and infrared light with pulsed electromagnetic frequencies.

Photobiomodulation with Near Infrared Light Helmet in a Pilot, Placebo Controlled Clinical Trial in Dementia Patients Testing Memory and Cognition.

Alzheimer's disease (AD) is a common, chronic expensive debilitating neurodegenerative disease with no current treatments to prevent the physical deterioration of the brain and the consequent cognitive deficits. The current pathophysiology of Alzheimer's disease is the accumulation of neurofibrillary tangles (NFTs) of hyperphosphorylated tau protein and amyloid-beta (Aß) plaques. Antibody therapy of Tau and Amyloid beta, vaccines and other methods to decrease Tau and or Amyloid have not been successful after considerable pharmaceutical and biotech efforts. For example, Eli Lilly announced a major change to its closely watched clinical trial for the Alzheimer's drug solanezumab which failed to reach statistical significance. Recently, a report on animal models using photomodulation with near infrared light to treat AD pathology in K369I tau transgenic model (K3) l engineered to develop neurofibrillary tangles, and the APPs/PSEN1dE9 transgenic model (APP/PS1) to develop amyloid plaques. Mice were treated with NIR 20 times over a four-week period and NIR treatment (600-1000 nm) was associated with a reduction in the size and number of amyloid-ß plaques in the neocortex and hippocampus. We now report a small pilot double blind, placebo-controlled trial (n=11) 6 active, 3 controls and 2 dropouts assessing the effect of 28 consecutive, sixminute transcranial sessions of near infrared (NIR) stimulation using 1060-1080 nm light emitting diodes. Subjects were independently diagnosed with dementia conducted in an outpatient behavioral healthcare clinic. IRB approval was obtained through the Quietmind Foundation's institutional review Board (IRB). Results showed changes in executive functioning; clock drawing, immediate recall, praxis memory, visual attention and task switching (Trails A&B) as well as a trend of improved EEG amplitude and connectivity measures. Neuroplasticity has also been reported with NIR light stimulation and mitochondrial enhancement.

Morton's foot and pyridoxal 5'-phosphate deficiency: genetically linked traits.

Vitamin B6 is an essential vitamin needed for many chemical reactions in the human body. It exists as several vitamins forms but pyridoxal 5'-phosphate (PLP) is the phosphorylated form needed for transamination, deamination, and decarboxylation. PLP is important in the production of neurotransmitters, acts as a Schiff base and is essential in the metabolism of homocysteine, a toxic amino acid involved in cardiovascular disease, stroke, thrombotic and Alzheimer's disease. This report announces the connection between a deficit of PLP with a genetically linked physical foot form known as the Morton's foot. Morton's foot has been associated with fibromyalgia/myofascial pain syndrome. Another gene mutation methylenetetrahydrofolate reductase (MTHFr) is now being recognized much commonly than previous with chronic fatigue, chronic Lyme diseases and as "the missing link" in other chronic diseases. PLP deficiency also plays a role in impaired glucose tolerance and may play a much bigger role in the obesity, diabetes, fatty liver and metabolic syndrome. Without the Schiff-base of PLP acting as an electron sink, storing electrons and dispensing them in the mitochondria, free radical damage occurs! The recognition that a phenotypical expression (Morton's foot) of a gene resulting in deficiency of an important cofactor enzyme pyridoxal 5'-phosphate will hopefully alert physicians and nutritionist to these phenomena. Supplementation with PLP, L5-MTHF, B12 and trimethylglycine should be used in those patients with hyperhomocysteinemia and/or MTHFR gene mutation.

Mitochondria of mice and men: moderate magnetic fields in obesity and fatty liver.

This paper reviews insulin resistance associated with fatty liver which accompanies the metabolic syndrome or diabetes from obesity. Until recently, one hypothesis that has received little attention is that mitochondrial defects are the cause of metabolic syndromes or diabetes 2, fatty liver and insulin resistance. Another hypothesis is that moderate magnetic fields change gene expression. Ob/Ob mice when treated with 0.5 T direct current electromagnetic fields were found to increase their activity, lose weight and fat in a 6 day period. Gene array analysis of human embryonic stem cells in another experiment of 0.23-0.28 T static magnetic fields was conducted. Up-regulation of genes for insulin factors genes, peroxisome proliferative activity receptor were increased, and calcium channel gene and other genes for mitochondrial ribosomal protein S, and uncoupling protein 2. Down-regulation of tumor necrosis factor alpha and interleukin 6 were demonstrated for this transformation. Forkhead transcription factors are also up-regulated at 5 days. Accelerated liver detoxification by moderate magnetic therapy of obesogens that disrupt homeostasis of metabolism of lipids ultimately resulting in obesity is another hypothesis.