BACKGROUND: Small aggregates (oligomers) of the toxic proteins amyloid-β (Aβ) and phospho-tau (p-tau) are essential contributors to Alzheimer's disease (AD). In mouse models for AD or human AD brain extracts, Transcranial Electromagnetic Treatment (TEMT) disaggregates both Aβ and p-tau oligomers, and induces brain mitochondrial enhancement. These apparent "disease-modifying" actions of TEMT both prevent and reverse memory impairment in AD transgenic mice. OBJECTIVE: To evaluate the safety and initial clinical efficacy of TEMT against AD, a comprehensive open-label clinical trial was performed. METHODS: Eight mild/moderate AD patients were treated with TEMT in-home by their caregivers for 2 months utilizing a unique head device. TEMT was given for two 1-hour periods each day, with subjects primarily evaluated at baseline, end-of-treatment, and 2 weeks following treatment completion. RESULTS: No deleterious behavioral effects, discomfort, or physiologic changes resulted from 2 months of TEMT, as well as no evidence of tumor or microhemorrhage induction. TEMT induced clinically important and statistically significant improvements in ADAS-cog, as well as in the Rey AVLT. TEMT also produced increases in cerebrospinal fluid (CSF) levels of soluble Aβ1-40 and Aβ1-42, cognition-related changes in CSF oligomeric Aβ, a decreased CSF p-tau/Aβ1-42 ratio, and reduced levels of oligomeric Aβ in plasma. Pre- versus post-treatment FDG-PET brain scans revealed stable cerebral glucose utilization, with several subjects exhibiting enhanced glucose utilization. Evaluation of diffusion tensor imaging (fractional anisotropy) scans in individual subjects provided support for TEMT-induced increases in functional connectivity within the cognitively-important cingulate cortex/cingulum. CONCLUSION: 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.

College of Pharmacy University of South Florida Tampa FL USA

Department of Neurology 2nd Faculty of Medicine Charles University Motol University Hospital Prague Czech Republic

Invicro Boston MA USA

Left Coast Engineering Escondido CA USA

NeuroEM Therapeutics Inc Phoenix AZ USA

Ocotillo Electromagnetics Inc Chandler AZ USA

RF Exposure Laboratory San Marcos CA USA

School of Aging Studies University of South Florida Tampa FL USA

University Diagnostic Institute Tampa FL USA

University of South Florida Health Byrd Alzheimer's Institute Tampa FL USA

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Emerging Alzheimer's disease treatment paradigms: A late-stage clinical trial review