Review of the Evidence that Transcranial Electromagnetic Treatment will be a Safe and Effective Therapeutic Against Alzheimer's Disease

Gary W Arendash, Gary W Arendash

Abstract

We have demonstrated in multiple studies that daily, long-term electromagnetic field (EMF) treatment in the ultra-high frequency range not only protects Alzheimer's disease (AD) transgenic mice from cognitive impairment, but also reverses such impairment in aged AD mice. Moreover, these beneficial cognitive effects appear to be through direct actions on the AD process. Based on a large array of pre-clinical data, we have initiated a pilot clinical trial to determine the safety and efficacy of EMF treatment to mild-moderate AD subjects. Since it is important to establish the safety of this new neuromodulatory approach, the main purpose of this review is to provide a comprehensive assessment of evidence supporting the safety of EMFs, particularly through transcranial electromagnetic treatment (TEMT). In addition to our own pre-clinical studies, a rich variety of both animal and cell culture studies performed by others have underscored the anticipated safety of TEMT in clinical AD trials. Moreover, numerous clinical studies have determined that short- or long-term human exposure to EMFs similar to those to be provided clinically by TEMT do not have deleterious effects on general health, cognitive function, or a variety of physiologic measures-to the contrary, beneficial effects on brain function/activity have been reported. Importantly, such EMF exposure has not been shown to increase the risk of any type of cancer in human epidemiologic studies, as well as animal and cell culture studies. In view of all the above, clinical trials of safety/efficacy with TEMT to AD subjects are clearly warranted and now in progress.

Keywords: Alzheimer’s disease; Aβ oligomers; cognition; electromagnetic treatment; memory; transcranial.

Figures

Fig.1
Fig.1
EMF treatment, begun in young adulthood, protects AD mice (Tg) mice from cognitive impairment and improves basic memory of normal mice. Cognitive interference testing at 4-5 months (A) and 6-7 months (B) into EMF treatment revealed overall [Tg and non-Tg(NT) animals combined] cognitive benefits at the initial test point and cognitive protection of Tg mice at the later test point during the first of two test Blocks. C) Proactive interference testing during Block 2 revealed both overall benefit (at 4-5 M) and cognitive protection of Tg mice (at 6-7M). *p < 0.05 versus other group(s) at same time point; †p < 0.05 versus Tg/EMF group. D) Normal (NT) mice at 6-7 months into EMF treatment showed superior Y-maze spontaneous alternation. *p < 0.05 versus all other groups.
Fig.2
Fig.2
At 8 months into EMF treatment, cognitively-impaired AD mice (Tg) mice exhibited cognitive benefits and reduced brain Aβ deposition. A) Cognitive interference testing revealed Tg/EMF mice as vastly superior to Tg controls in 3-trial recall and retroactive interference performance. Even non-transgenic (NT) mice receiving EMF exposure showed better recall performance than NT controls, particularly early in recall testing. The final 2-day block of testing is shown from four days of testing. Upper graph: *p < 0.025 versus control; Lower graph: *p < 0.05 or higher level of significance versus control. B) Long-term EMF treatment significantly reduced total Aβ deposition in entorhinal cortex and hippocampus of Tg mice. Photomicrographic examples of typical Aβ immunostained-plaques from Tg and Tg/EMF mice are provided. *p < 0.02 versus Tg control group. Scale bar = 50 μm.
Fig.3
Fig.3
In Vitro EMF treatment of hippocampal homogenates from aged Tg mice results in progressively decreased Aβ oligomerization between 3 and 6 days into treatment. Western blots display the 80 kDa Aβ oligomer on top and the β-Actin protein control on bottom. Left panel shows non-treated Tg controls of progressive Aβ aggregation, while right panel shows the same homogenates treated with EMF through 6 days.
Fig.4
Fig.4
Long-term EMF treatment of aged AD (Tg) mice dramatically increased soluble Aβ1–40 levels in mitochondria preparations from both cortex and hippocampus. These 5–10x increases in mitochondrial Aβ are consistent with an EMF-induced disaggregation of toxic Aβ oligomers associated with intraneuronal mitochondria.
Fig.5
Fig.5
EMF treatment greatly enhances mitochondrial function within both cerebral cortex and hippocampus of aged AD (Tg) mice. Shown are percent changes across six measures of mitochondrial function, wherein 50–150% enhancements were induced by EMF treatment.
Fig.6
Fig.6
TEMT increases neuronal activity in entorhinal cortex of aged AD mice, as indicated by the number of cFos-stained neurons. Note increased number of active neurons in AD mice given long-term TEMT (right) compared to control AD mice not given TEMT (left). For AD and normal mice, average number of c-Fos-stained neurons in entorhinal cortex from five representative fields increased from 83 neurons per field in controls to 100 neurons per field after TEMT (↑21%; p < 0.02).
Fig.7
Fig.7
An FDTD computer simulation showing deep electric field penetration by an excitation element (one of eight elements) positioned on the cranium. Deep brain regions, such as the hippocampus and entorhinal cortex, are easily affected by this single element.
Fig.8
Fig.8
A, B) There are no changes in brain temperature of AD transgenic mice (both APPsw and APPsw+PS1) and normal mice (NT) during acute EMF treatment (two 1-h treatments during a single day) compared naïve Tg and NT mice of various ages. C) The strong correlation between brain and body temperature, with brain temperature typically being 0.3-0.4°C cooler.
Fig.9
Fig.9
Body and brain temperature measurements for AD mice recorded prior to the start of EMF treatment (control), as well as at 5 days and 12 days into EMF treatment. For both control and treatment time points, there were no differences between EMF-treated and control AD mice for either body or brain temperatures. As well, no significant differences in OFF versus ON temperatures were evident in EMF-treated AD mice.

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Source: PubMed

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