title: An innovative intervention for the treatment of cognitive impairment-Emisymmetric bilateral stimulation improves cognitive functions in Alzheimer's disease and mild cognitive impairment: an open-label study.
abstract: OBJECTIVE
  In the last decade, the development of different methods of brain stimulation by electromagnetic fields (EMF) provides a promising therapeutic tool for subjects with impaired cognitive functions. Emisymmetric bilateral stimulation (EBS) is a novel and innovative EMF brain stimulation, whose working principle is to introduce very weak noise-like stimuli through EMF to trigger self-arrangements in the cortex of treated subjects, thereby improving cognitive faculties. The aim of this pilot study was to investigate in patients with cognitive impairment the effectiveness of EBS treatment with respect to global cognitive function, episodic memory, and executive functions.
  
  
  METHODS
  Fourteen patients with cognitive decline (six with mild cognitive impairment and eight with Alzheimer's disease) underwent three EBS applications per week to both the cerebral cortex and auricular-specific sites for a total of 5 weeks. At baseline, after 2 weeks and 5 weeks, a neuropsychological assessment was performed through mini-mental state examination, free and cued selective reminding tests, and trail making test. As secondary outcomes, changes in behavior, functionality, and quality of life were also evaluated.
  
  
  RESULTS
  After 5 weeks of standardized EBS therapy, significant improvements were observed in all neurocognitive assessments. Mini-mental state examination score significantly increased from baseline to end treatment (+3.19, P=0.002). Assessment of episodic memory showed an improvement both in immediate and delayed recalls (immediate recall =+7.57, P=0.003; delayed recall =+4.78, P<0.001). Executive functions significantly improved from baseline to end stimulation (trail making test A -53.35 seconds; P=0.001). Of note, behavioral disorders assessed through neuropsychiatric inventory significantly decreased (-28.78, P<0.001). The analysis concerning the Alzheimer's disease and mild cognitive impairment group confirmed a significant improvement of cognitive functions and behavior after EBS treatment.
  
  
  CONCLUSIONS
  This pilot study has shown EBS to be a promising, effective, and safe tool to treat cognitive impairment, in addition to the drugs presently available. Further investigations and controlled clinical trials are warranted.
authors.affiliation: Department of Internal Medicine and Medical Therapy, Section of Geriatrics, University of Pavia, Pavia, Italy ; Agency for Elderly People Services, Santa Margherita Hospital, Pavia, Italy ; Ambra Elektron, Italian Association of Biophysics for the Study of Electromagnetic Fields in Medicine, Turin, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Guerriero
authors.affiliation: Ambra Elektron, Italian Association of Biophysics for the Study of Electromagnetic Fields in Medicine, Turin, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Botarelli
authors.affiliation: Ambra Elektron, Italian Association of Biophysics for the Study of Electromagnetic Fields in Medicine, Turin, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Mele
authors.affiliation: Ambra Elektron, Italian Association of Biophysics for the Study of Electromagnetic Fields in Medicine, Turin, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Polo
authors.affiliation: Ambra Elektron, Italian Association of Biophysics for the Study of Electromagnetic Fields in Medicine, Turin, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Zoncu
authors.affiliation: Ambra Elektron, Italian Association of Biophysics for the Study of Electromagnetic Fields in Medicine, Turin, Italy ; Alberto Sorti Research Institute, Medicine and Metamolecular Biology, Turin, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Renati
authors.affiliation: Department of Internal Medicine and Medical Therapy, Section of Geriatrics, University of Pavia, Pavia, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Sgarlata
authors.affiliation: Agency for Elderly People Services, Santa Margherita Hospital, Pavia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Rollone
authors.affiliation: Department of Internal Medicine and Medical Therapy, Section of Geriatrics, University of Pavia, Pavia, Italy ; Agency for Elderly People Services, Santa Margherita Hospital, Pavia, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ricevuti
authors.affiliation: Department of Internal Medicine and Medical Therapy, Section of Geriatrics, University of Pavia, Pavia, Italy.
authors.forename: Niccolo
authors.initials: N
authors.lastname: Maurizi
authors.affiliation: Department of Internal Medicine and Medical Therapy, Section of Geriatrics, University of Pavia, Pavia, Italy.
authors.forename: Matthew
authors.initials: M
authors.lastname: Francis
authors.affiliation: Department of Public Health, Experimental and Forensic Medicine, Section of Human Nutrition, Endocrinology and Nutrition Unit, University of Pavia, Pavia, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Rondanelli
authors.affiliation: Department of Public Health, Experimental and Forensic Medicine, Section of Human Nutrition, Endocrinology and Nutrition Unit, University of Pavia, Pavia, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Perna
authors.affiliation: Agency for Elderly People Services, Santa Margherita Hospital, Pavia, Italy ; Department of Public Health, Experimental and Forensic Medicine, Biostatistics and Clinical Epidemiology Unit, University of Pavia, Pavia, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Guido
authors.affiliation: Ambra Elektron, Italian Association of Biophysics for the Study of Electromagnetic Fields in Medicine, Turin, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Mannu
keywords: Alzheimer’s disease; Emisymmetric bilateral stimulation; cognitive decline; pulsed electromagnetic fields