Researchers here report on a small clinical trial of a form of electromagnetic stimulation, claiming reduction in amyloid burden and improvement in cognitive function in Alzheimer's patients. Other approaches to electromagnetic stimulation have been tested in human trials for Alzheimer's disease and failed; the authors here argue that the details of the methodology used matter greatly. It is not unreasonable to expect electromagnetic fields to have effects on cellular metabolism, and there are a range of efforts to try to affect everything from neurodegeneration to wound healing via this class of approach. There is always the question of mechanisms, however: determining how exactly it might be working to affect amyloid levels and cellular behavior, after an effect is confirmed, is a challenging task.

In view of the inability of drugs to slow or reverse the cognitive impairment of Alzheimer's disease (AD) thus far, investigating non-pharmaceutic interventions against AD as a possible alternative is now clearly warranted. Neuromodulatory approaches have consequently emerged and are currently being clinically tested in AD subjects. These approaches include transcranial magnetic stimulation (tMS), transcranial direct current stimulation, and deep brain stimulation. All three approaches provide a generalized stimulatory/inhibitory effect on neuronal activity. The most recent and largest clinical studies involving long-term tMS (Phase III clinical trial) or deep brain stimulation (Phase II clinical trial) in AD subjects have reported minimal or no cognitive benefits.

As the newest neuromodulatory approach against AD, Transcranial Electromagnetic Treatment (TEMT) is very different from tMS because TEMT involves perpendicular magnetic and electric waves emanating away from an antenna/emitter source (rather than magnetic waves radiating from and returning to a conductor in tMS). For our studies, these "electromagnetic waves" are actually within the radiofrequency range (around 1 GHz), which can easily penetrate the human cranium and underlying brain areas.

In a number of pre-clinical studies involving AD transgenic mice, we have administered TEMT daily for up to 8 months. We have demonstrated the ability of TEMT to prevent/reverse both oligomeric and insoluble amyloid-β aggregation - both inside and outside neurons. These TEMT-induced reductions in brain Aβ aggregation are accompanied by brain mitochondrial enhancement and prevention or reversal of cognitive impairment in AD transgenic mice at multiple age. In view of our extensive pre-clinical platform and the aforementioned wide spectrum of human safety studies, clinical trials of TEMT technology in AD were clearly warranted. Therefore, we designed and built a first-of-its-kind head device for administration of TEMT to human subjects in their homes and by their caregivers. The present study reports on safety and efficacy endpoints in an open-label clinical trial to provide daily TEMT to AD subjects over a 2-month period, as well as evaluation at two weeks following completion of treatment.

No deleterious behavioral effects, discomfort, or physiologic changes resulted from 2 months of TEMT. TEMT induced clinically important and statistically significant improvements in the Alzheimer's Disease Assessment Scale-Cognitive, as well as in the Rey Auditory Verbal Learning Test. TEMT also produced increases in cerebrospinal fluid (CSF) levels of soluble amyloid-β, cognition-related changes in CSF oligomeric amyloid-β, a decreased CSF phosphorylated-tau/amyloid-β ratio, and reduced levels of oligomeric amyloid-β in plasma. TEMT administration to AD subjects appears to be safe, while providing cognitive enhancement, changes to CSF/blood AD markers, and evidence of stable/enhanced brain connectivity.