Pulsed electromagnetic field therapy for Alzheimer’s is applied as rTMS repetitive transcranial magnetic stimulation; i.e. very strong pulsed electromagnetic field therapy (PEMF) directly to the head. Research proves pulsed electromagnetic field therapies (PEMF) have beneficial effects upon Alzheimer’s disease and its underlying neurophysiological abnormality.


Research into PEMF on the brain called repetitive transcranial magnetic stimulation or rTMS on Alzheimer’s is poorly investigated compared to Parkinson’s. To date there are no approved methods of using rTMS for Alzheimer’s although Anninos PA, Sandyk R and Jacobson JI the three pioneers of picoTesla electromagnetic field therapy; continue to successfully treat Alzheimer’s as well as Parkinson’s and epilepsy.

While these researchers attribute their effects to changing brain-wave characteristics (due to well established principal of brain wave entrainment), we believe since Jacobson, Sandyk and Anninos primary use frequencies within range of main Schumann 7-8 Hz, the effects at least partially are attributed to MoreATP in the grey matter and at nerve synapses as a frequency specific effect to the magnetic fields applied. Read Schumann Waves and Psychobiology.

The neurological system (entire body) operates via electric and electromagnetic signals. Does it not make sense to address neurological disease states such as Alzheimer’s from an electrophysiological or electrochemical rather than from a chemical based point of view? Researchers continue to declare ‘YEARS’ before meaningful rTMS treatment for Alzheimer’s sufferers when the researchers below have already proved at least some therapeutic intervention.

We believe that low-level magnetic stimulation during sleep every night is superior to huge amounts of stimulation over short course of days or weeks as in these studies below.

50 years of pulsed electromagnetic field therapy research suggests that some sort type of electrophysiological deficit exists in neurological disease states and that it should be addressed via same electrophysiological channel. It could be simply loss in cell membrane voltage potential in the brain causing the changes in brain tissue, or a combination of that with loss of optimum brain-wave rhythm

The addressable conditions for which there is pulsed electromagnetic field (PEMF) therapy peer reviewed research; include (but are not limited to) epilepsy, Parkinson’s, migraine, cluster and other headache syndromes, severe PMS, attention deficit disorder ADD, attention deficit hyperactivity disorder ADHD, autism and autistic / autism spectrum disorders, depression, schizophrenia, anxiety, insomnia and sleeping disorders in general, muscle twitch, tremor disorders, muscle weakness, chronic wounds, bone non-unions and endometriosis.

Several hundred pulsed electromagnetic field therapy citations contained in our research bibliographies below are linked directly to PubMed a service of the U.S. National Library of Medicine and the U.S. National Institutes of Health.

The magnetic therapy Alzheimer’s rTMS bibliography is offered for your education only and are not intended as promotional material for our Pulsed Magnetic technology.

EarthPulse™ PEMF Disclaimer:

Peer-reviewed studies, PEMF customer reviews, videos, papers and links provided [the Information] on this website site and others we link to are not offered to suggest or imply that you will achieve similar results with use of the EarthPulse™ Pulsed electromagnetic field and electrical stimulation devices and methods. The information is for reference purposes only and not intended to recommend our pulsed electromagnetic field device system as a drug or as a diagnosis for any illness or disease condition; nor as a product to eliminate disease or other medical condition.

The Information has not been evaluated by U.S. Food and Drug Administration. Worldwide, there are no governmental health agencies that recognize a need to enhance natural magnetic fields using pulsed electromagnetic fields.

The Information and opinions provided on our website are based upon reputably published journals and first hand experience. The Information and opinions expressed anywhere on our web site or in printed materials or in videos are never to be construed as medical advice. This website, company, and its contractors, employees, organisers, participants, practitioners, promoters, or affiliates or its suppliers and vendors make no warranty of any kind, expressed or implied with regard to the Information or how you choose to use it.

Magnetic Therapy Bahamas, Ltd. / Sleep Tech Intl. / EarthPulse Technologies, LLC make no medical claims, real or implied, as to benefit of our device and methods. Our product is not intended to be used to diagnose, treat, cure or prevent any disease. Readers should consult appropriate health professionals on any matter relating to their health and well-being. Readers accept all responsibility for self-experimentation.


Magnetic Therapy Alzheimer’s; Repetitive Transcranial Magnetic Stimulation (rTMS) Bibliography

To read the original at Pubmed copy the title and paste into the search box.

A Case for rTMS in Late Life Depression with Comorbid Alzheimer’s Dementia.
Kerns SE, Bess J, Melman K.
Brain Stimul. 2016 Jan-Feb;9(1):151-2. doi: 10.1016/j.brs.2015.11.002. Epub 2015 Dec 10. No abstract available.
PMID: 26710677

Treatment of Alzheimer’s Disease with Repetitive Transcranial Magnetic Stimulation Combined with Cognitive Training: A Prospective, Randomized, Double-Blind, Placebo-Controlled Study.
Lee J, Choi BH, Oh E, Sohn EH, Lee AY.
J Clin Neurol. 2016 Jan;12(1):57-64. doi: 10.3988/jcn.2016.12.1.57. Epub 2015 Sep 11.
PMID: 26365021 Free PMC Article

Effects of noninvasive brain stimulation on cognitive function in healthy aging and Alzheimer’s disease: a systematic review and meta-analysis.
Hsu WY, Ku Y, Zanto TP, Gazzaley A.
Neurobiol Aging. 2015 Aug;36(8):2348-59. doi: 10.1016/j.neurobiolaging.2015.04.016. Epub 2015 May 1. Review.
PMID: 26022770

Effects of Repetitive Transcranial Magnetic Stimulation in the Rehabilitation of Communication and Deglutition Disorders: Systematic Review of Randomized Controlled Trials.
Gadenz CD, Moreira Tde C, Capobianco DM, Cassol M.
Folia Phoniatr Logop. 2015;67(2):97-105. doi: 10.1159/000439128. Epub 2015 Nov 19.
PMID: 26580744 Free Article

Altered Cortical Synaptic Plasticity in Response to 5-Hz Repetitive Transcranial Magnetic Stimulation as a New Electrophysiological Finding in Amnestic Mild Cognitive Impairment Converting to Alzheimer’s Disease: Results from a 4-year Prospective Cohort Study.
Trebbastoni A, Pichiorri F, D’Antonio F, Campanelli A, Onesti E, Ceccanti M, de Lena C, Inghilleri M.
Front Aging Neurosci. 2016 Jan 12;7:253. doi: 10.3389/fnagi.2015.00253. eCollection 2015.
PMID: 26793103 Free PMC Article

Repetitive Transcranial Magnetic Stimulation as an Alternative Therapy for Cognitive Impairment in Alzheimer’s Disease: A Meta-Analysis.
Liao X, Li G, Wang A, Liu T, Feng S, Guo Z, Tang Q, Jin Y, Xing G, McClure MA, Chen H, He B, Liu H, Mu Q.
J Alzheimers Dis. 2015;48(2):463-72. doi: 10.3233/JAD-150346.
PMID: 26402010

Distinct Pattern of Gray Matter Atrophy in Mild Alzheimer’s Disease Impacts on Cognitive Outcomes of Noninvasive Brain Stimulation.
Anderkova L, Eliasova I, Marecek R, Janousova E, Rektorova I.
J Alzheimers Dis. 2015;48(1):251-60. doi: 10.3233/JAD-150067.
PMID: 26401945

Short and Long-term Effects of rTMS Treatment on Alzheimer’s Disease at Different Stages: A Pilot Study.
Rutherford G, Lithgow B, Moussavi Z.
J Exp Neurosci. 2015 Jun 3;9:43-51. doi: 10.4137/JEN.S24004. eCollection 2015.
PMID: 26064066 Free PMC Article

Transcranial magnetic stimulation to understand pathophysiology and as potential treatment for neurodegenerative diseases.
Ni Z, Chen R.
Transl Neurodegener. 2015 Nov 16;4:22. doi: 10.1186/s40035-015-0045-x. eCollection 2015. Review.
PMID: 26579223 Free PMC Article
Similar articles

J Neurol Sci. 2014 Nov 15;346(1-2):318-22. doi: 10.1016/j.jns.2014.08.036. Epub 2014 Aug 29.
Non-invasive brain stimulation of the right inferior frontal gyrus may improve attention in early Alzheimer’sdisease: A pilot study.
Eliasova I1, Anderkova L1, Marecek R1, Rektorova I2.

Neuroimage. 2014 Jan 15;85 Pt 3:948-60. doi: 10.1016/j.neuroimage.2013.05.117. Epub 2013 Jun 4.
Therapeutic effects of non-invasive brain stimulation with direct currents (tDCS) in neuropsychiatric diseases.
Kuo MF1, Paulus W, Nitsche MA.

J Neurosci Res. 2014 Jun;92(6):761-71. doi: 10.1002/jnr.23361. Epub 2014 Feb 12.
Pulsed electromagnetic fields potentiate neurite outgrowth in the dopaminergic MN9D cell line.
Lekhraj R1, Cynamon DE, DeLuca SE, Taub ES, Pilla AA, Casper D.

Low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) reverses Aβ(1-42)-mediated memory deficits in rats. Tan T, Xie J, Liu T, Chen X, Zheng X, Tong Z, Tian X.

Exp Gerontol. 2013 Aug;48(8):786-94. doi: 10.1016/j.exger.2013.05.001. Epub 2013 May 9.
Transcranial magnetic stimulation of degenerating brain: a comparison of normal aging, Alzheimer’s, Parkinson’s and Huntington’s disease. Ljubisavljevic MR, Ismail FY, Filipovic S.

Curr Alzheimer Res. 2013 Jul;10(6):578-96.
J Neural Transm. 2013 May;120(5):813-9. doi: 10.1007/s00702-012-0902-z. Epub 2012 Oct 18.Repetitive transcranial magnetic stimulation combined with cognitive training is a safe and effective modality for the treatment ofAlzheimer’s disease: a randomized, double-blind study.Rabey JM, Dobronevsky E, Aichenbaum S, Gonen O, Marton RG, Khaigrekht M.

Source Department of Neurology, Assaf Harofeh Medical Center, Zerifin, 70300,Israel.
Abstract: Cortical excitability can be modulated using repetitive transcranial magnetic stimulation (rTMS). Previously, we showed that rTMS combined with cognitive training (rTMS-COG) has positive results in Alzheimer’s disease (AD). The goal of this randomized double-blind, controlled study was to examine the safety and efficacy of rTMS-COG in AD. Fifteen AD patients received 1-h daily rTMS-COG or sham treatment (seven treated, eight placebo), five sessions/week for 6 weeks, followed by biweekly sessions for 3 months. The primary outcome was improvement of the cognitive score. The secondary outcome included improvement in the Clinical Global Impression of Change (CGIC) and Neuropsychiatric Inventory (NPI). There was an improvement in the average ADAS-cog score of 3.76 points after 6 weeks in the treatment group compared to 0.47 in the placebo group and 3.52 points after 4.5 months of treatment, compared to worsening of 0.38 in the placebo (P = 0.04 and P = 0.05, respectively). There was also an improvement in the average CGIC score of 3.57 (after 6 weeks) and 3.67 points (after 4.5 months), compared to 4.25 and 4.29 in the placebo group (mild worsening) (P = 0.05 and P = 0.05, respectively). NPI improved non-significantly. In summary, the NeuroAD system offers a novel, safe and effective therapy for improving cognitive function in AD.

Eur J Neurol. 2012 Nov;19(11):1404-12. doi: 10.1111/j.1468-1331.2012.03699.x. Epub 2012 Mar 21.
Prefrontal cortex rTMS enhances action naming in progressive non-fluent aphasia.Cotelli M, Manenti R, Alberici A, Brambilla M, Cosseddu M, Zanetti O, Miozzo A, Padovani A, Miniussi C, Borroni B.Source IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
Progressive non-fluent aphasia (PNFA) is a neurodegenerative disorder that is characterized by non-fluent speech with naming impairment and grammatical errors. It has been recently demonstrated that repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) improves action naming in healthy subjects and in subjects with Alzheimer’s disease.
CONCLUSIONS: Our study demonstrated that rTMS improved action naming in subjects with PNFA, possibly due to the modulation of DLPFC pathways and a facilitation effect on lexical retrieval processes. Future studies on the potential of a rehabilitative protocol using rTMS applied to the DLPFC in this orphan disorder are required.

IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.Neuropsychol Rehabil. 2011 Oct;21(5):717-41. Anomia training and brain stimulation in chronic aphasia. Cotelli M, Fertonani A, Miozzo A, Rosini S, Manenti R, Padovani A, Ansaldo AI, Cappa SF, Miniussi C.Source a IRCCS Centro San Giovanni di Dio Fatebenefratelli , Brescia , Italy.

J Neurol. 2012 Jan;259(1):83-92. doi: 10.1007/s00415-011-6128-4. Epub 2011 Jun 14.
Effects of low versus high frequencies of repetitive transcranial magnetic stimulation on cognitive function and cortical excitability in Alzheimer’s dementia.
Ahmed MA, Darwish ES, Khedr EM, El Serogy YM, Ali AM.
Department of NeuroPsychiatry, Assiut University Hospital, Assiut, Egypt.
Abstract: The aim of the study was to compare the long-term efficacy of high versus low frequency repetitive transcranial magnetic stimulation (rTMS), applied bilaterally over the dorsolateral prefrontal cortex (DLPFC), on cognitive function and cortical excitability of patients with Alzheimer’s disease (AD). Forty-five AD patients were randomly classified into three groups. The first two groups received real rTMS over the DLPFC(20 and 1 Hz, respectively) while the third group received sham stimulation. All patients received one session daily for five consecutive days. In each session, rTMS was applied first over the right DLPFC, immediately followed by rTMS over the left DLPFC. Mini Mental State Examination (MMSE), Instrumental Daily Living Activity (IADL) scale and the Geriatric Depression Scale (GDS) were assessed before, after the last (fifth) session, and then followed up at 1 and 3 months. Neurophysiological evaluations included resting and active motor threshold (rMT and aMT), and the duration of transcallosal inhibition (TI) before and after the end of the treatment sessions. At base line assessment there were no significant differences between groups in any of the rating scales. The high frequency rTMS group improved significantly more than the low frequency and sham groups in all rating scales (MMSE, IADL, and GDS) and at all time points after treatment. Measures of cortical excitability immediately after the last treatment session showed that treatment with 20 Hz rTMS reduced TI duration.These results confirm that five daily sessions of high frequency rTMS over the left and then the right DLPFC improves cognitive function in patients with mild to moderate degree of AD. This improvement was maintained for 3 months. High frequency rTMS may be a useful addition to therapy for the treatment of AD.

A case report of daily left prefrontal repetitive transcranial magnetic stimulation (rTMS) as an adjunctive treatment for Alzheimer disease. Haffen E, Chopard G, Pretalli JB, Magnin E, Nicolier M, Monnin J, Galmiche J, Rumbach L, Pazart L, Sechter D, Vandel P.
Brain Stimul. 2012 Jul;5(3):264-6. doi: 10.1016/j.brs.2011.03.003. Epub 2011 Mar 30. No abstract available. Neuropsychol Rehabil. 2011 Oct;21(5):703-16. Epub 2011 Sep 26.
Non-invasive brain stimulation to assess and modulate neuroplasticity in Alzheimer’s disease.
Boggio PS, Valasek CA, Campanhã C, Giglio AC, Baptista NI, Lapenta OM, Fregni F.
a Social and Cognitive Neuroscience Laboratory and Developmental Disorders Program, Center for Health and Biological Sciences , Mackenzie Presbyterian University , Sao Paulo , Brazil.

J Neurol Neurosurg Psychiatry. 2011 Jul;82(7):794-7. Epub 2010 Jun 23.
Improved language performance in Alzheimer disease following brain stimulation.
Cotelli M, Calabria M, Manenti R, Rosini S, Zanetti O, Cappa SF, Miniussi C.
IRCCS Centro San Giovanni di Dio Fatebenefratelli, Via Pilastroni, 4, Brescia 25125, Italy;

J Neurol. 2011 Jun 14. [Epub ahead of print]
Effects of low versus high frequencies of repetitive transcranial magnetic stimulation on cognitive function and cortical excitability in Alzheimer’s dementia.
Ahmed MA, Darwish ES, Khedr EM, El Serogy YM, Ali AM.
Department of NeuroPsychiatry, Assiut University Hospital, Assiut, Egypt.

J Neural Transm. 2011 Mar;118(3):463-71. Epub 2011 Jan 19.
Beneficial effect of repetitive transcranial magnetic stimulation combined with cognitive training for the treatment of Alzheimer’s disease: a proof of concept study.
Bentwich J, Dobronevsky E, Aichenbaum S, Shorer R, Peretz R, Khaigrekht M, Marton RG, Rabey JM.
Neuronix Ltd, Yokneam, Israel.
Dement Geriatr Cogn Disord. 2011;31(1):71-80. Epub 2011 Jan 14.
A review of transcranial magnetic stimulation in vascular dementia.
Pennisi G, Ferri R, Cantone M, Lanza G, Pennisi M, Vinciguerra L, Malaguarnera G, Bella R.
Department of Neuroscience, University of Catania, Catania, Italy

Brain Lang. 2010 Apr;113(1):45-50. Epub 2010 Feb 16.
Stimulating conversation: enhancement of elicited propositional speech in a patient with chronic non-fluent aphasia following transcranial magnetic stimulation.
Hamilton RH, Sanders L, Benson J, Faseyitan O, Norise C, Naeser M, Martin P, Coslett HB.
Laboratory for Cognition and Neural Stimulation, Department of Neurology, University of Pennsylvania, Philadelphia, PA 19104, USA

Front Aging Neurosci. 2010 Nov 24;2:151.
Action and Object Naming in Physiological Aging: An rTMS Study.
Cotelli M, Manenti R, Rosini S, Calabria M, Brambilla M, Bisiacchi PS, Zanetti O, Miniussi C.
Istituto Di Ricovero e Cura a Carattere Scientifico, Centro San Giovanni di Dio Fatebenefratelli Brescia, Italy.

J Rehabil Med. 2010 Nov;42(10):973-8.
Effect of repetitive transcranial magnetic stimulation in a patient with chronic crossed aphasia: fMRI study.
Jung TD, Kim JY, Lee YS, Kim DH, Lee JJ, Seo JH, Lee HJ, Chang Y.
Department of Physical Medicine and Rehabilitation, Kyungpook National University Hospital/Kyungpook National University School of Medicine, 200 Dongduk-Ro Jung-Gu Daegu, Korea.

Restor Neurol Neurosci. 2010;28(4):511-29.
Research with rTMS in the treatment of aphasia.
Naeser MA, Martin PI, Treglia E, Ho M, Kaplan E, Bashir S, Hamilton R, Coslett HB, Pascual-Leone A.
Veterans Affairs Boston Healthcare System and the Harold Goodglass Boston University Aphasia Research Center, Department of Neurology, Boston University School of Medicine, Boston, MA 02130, USA.

Am J Med Sci. 2010 Mar;339(3):249-57.
Carbonic anhydrase I, II, and VI, blood plasma, erythrocyte and saliva zinc and copper increase after repetitive transcranial magnetic stimulation.
Henkin RI, Potolicchio SJ, Levy LM, Moharram R, Velicu I, Martin BM.
Taste and Smell Clinic, Washington, District of Columbia 20016, USA.

Cogn Behav Neurol. 2010 Mar;23(1):29-38.
Improved language in a chronic nonfluent aphasia patient after treatment with CPAP and TMS.
Naeser MA, Martin PI, Lundgren K, Klein R, Kaplan J, Treglia E, Ho M, Nicholas M, Alonso M, Pascual-Leone A.
Department of Neurology, Harold Goodglass Boston University Aphasia Research Center, Boston University School of Medicine and the Veterans Affairs Boston Healthcare System, Boston, MA 02130, USA.

J Neural Transm. 2010 Jan;117(1):105-22. Epub 2009 Oct 27.
Cognitive effects of high-frequency repetitive transcranial magnetic stimulation: a systematic review.
Guse B, Falkai P, Wobrock T.
Department of Psychiatry and Psychotherapy, Georg-August-University Göttingen, Von-Siebold-Strasse 5, 37075, Gottingen, Germany.

Curr Neurol Neurosci Rep. 2009 Nov;9(6):451-8.
Research with transcranial magnetic stimulation in the treatment of aphasia.
Martin PI, Naeser MA, Ho M, Treglia E, Kaplan E, Baker EH, Pascual-Leone A.
Aphasia Research Center 12-A, VA Boston Healthcare System, Boston, MA 02130, USA

J Neuroeng Rehabil. 2009 Mar 17;6:8.
Using non-invasive brain stimulation to augment motor training-induced plasticity.
Bolognini N, Pascual-Leone A, Fregni F.
Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA.

Eur J Neurol. 2008 Dec;15(12):1286-92.
Transcranial magnetic stimulation improves naming in Alzheimer disease patients at different stages of cognitive decline.
Cotelli M, Manenti R, Cappa SF, Zanetti O, Miniussi C.
Source IRCCS S. Giovanni di Dio Fatebenefratelli, Brescia, Italy.

Brain Stimul. 2008 Oct;1(4):363-9. Epub 2008 Oct 7.
Consensus: Can transcranial direct current stimulation and transcranial magnetic stimulation enhance motor learning and memory formation?
Reis J, Robertson EM, Krakauer JW, Rothwell J, Marshall L, Gerloff C, Wassermann EM, Pascual-Leone A, Hummel F, Celnik PA, Classen J, Floel A, Ziemann U, Paulus W, Siebner HR, Born J, Cohen LG.
Human Cortical Physiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1430, USA.

Methods. 2008 Apr;44(4):329-37.
Noninvasive brain stimulation with transcranial magnetic or direct current stimulation (TMS/tDCS)-From insights into human memory to therapy of its dysfunction.
Sparing R, Mottaghy FM.
Institute of Neuroscience and Biophysics, Research Centre Juelich, Juelich, Germany.

Brain Stimul. 2008 Apr;1(2):97-105. Epub 2007 Dec 3.
Comparatively weak after-effects of transcranial alternating current stimulation (tACS) on cortical excitability in humans.
Antal A, Boros K, Poreisz C, Chaieb L, Terney D, Paulus W.
Department of Clinical Neurophysiology, Georg-August University, Göttingen, Germany

Arch Neurol. 2006 Nov;63(11):1602-4.
Effect of transcranial magnetic stimulation on action naming in patients with Alzheimer disease.
Istituto di Recovero e Cura a Carattere Scientifico San Giovanni di Dio Fatebenefratelli, University of Brescia, Brescia, Italy.

J Neurol Sci. 2005 Mar 15;229-230:157-61. Epub 2004 Dec 16.
Cognitive functioning after repetitive transcranial magnetic stimulation in patients with cerebrovascular disease without dementia: a pilot study of seven patients.
First Department of Neurology, Masaryk University, Teaching Hospital sv. Anna, Pekarska 53, 656 91, Brno, Czech Republic

Ann Neural. 2003 Jun;53(6):824; author reply 824-5.
Motor cortex hyperexcitability to transcranial magnetic stimulation in Alzheimer’s disease: evidence of impaired glutamatergic neurotransmission?
Di Lazzaro V, Oliviero A, Pilato F, Saturno E, Dileone M, Tonali PA.
Publication Types:
* Comment
* Letter
PMID: 12783435
Ann Neurol. 2003 Jan;53(1):102-8.
Motor cortex excitability in Alzheimer’s disease: A transcranial magnetic stimulation study.
Ferreri F, Pauri F, Pasqualetti P, Fini R, Dal Forno G, Rossini PM.
Department of Neurology, University Campus Biomedico.
Motor deficits affect patients with Alzheimer’s disease only at later stages. Recent studies demonstrate that the primary motor cortex is affected by neuronal degeneration accompanied by the formation of amyloid plaques and neurofibrillary tangles. It is conceivable that neuronal loss is compensated by reorganization of the neural circuitries occurring along the natural course of the disease, thereby maintaining motor performances in daily living. Cortical motor output to upper limbs was tested via motor-evoked potentials from forearm and hand muscles elicited by transcranial magnetic stimulation of motor cortex in 16 patients with mild Alzheimer’s disease without motor deficits. Motor cortex excitability was increased, and the center of gravity of motor cortical output, as represented by excitable scalp sites, showed a frontal and medial shift, without correlated changes in the site of maximal excitability (hot-spot). This may indicate functional reorganization, possibly after the neuronal loss in motor areas. Hyperexcitability might be caused by a dysregulation of the intracortical GABAergic inhibitory circuitries and selective alteration of glutamatergic neurotransmission. Such findings suggest that motor cortex hyperexcitability and reorganization allows prolonged preservation of motor function during the clinical course of Alzheimer’s disease.
PMID: 12509853 [PubMed – in process]

Neurosci Lett. 2002 Sep 6;329(3):293-6.
Motor cortex excitability in Alzheimer disease: one year follow-up study.
Pennisi G, Alagona G, Ferri R, Greco S, Santonocito D, Pappalardo A, Bella R.
Department of Neurological Sciences, University of Catania, Azienda Policlinico dell’ Universita, Via S. Sofia, 78, 95123 Catania, Italy.
Seventeen patients affected by Alzheimer disease (AD) underwent two transcranial magnetic stimulation (TMS) studies separated by an interval of 12 months, in order to monitor possible changes in motor cortex excitability. After the first examination, all patients were treated with cholinesterase inhibitor drugs. Motor threshold (MT), amplitude of motor evoked potentials and central motor conduction time were considered. After one year, the mean MT values showed a decrease significantly correlated with the severity of cognitive involvement, evaluated by means of the Mini Mental State Examination (MMSE). The difference in MT between the two recording sessions showed no significant correlation with the difference in MMSE score. One year of treatment with cholinesterase inhibitor drugs did not stop the progressive increase in motor cortex excitability. Serial analysis of TMS might represent a method to monitor the rate of change in motor cortex excitability in patients with AD.
PMID: 12183034

Neurology. 2002 Aug 13;59(3):392-7.
Noninvasive in vivo assessment of cholinergic cortical circuits in AD using transcranial magnetic stimulation.
Di Lazzaro V, Oliviero A, Tonali PA, Marra C, Daniele A, Profice P, Saturno E, Pilato F, Masullo C, Rothwell JC.
Institute of Neurology, Catholic University, Largo A. Gemelli 8, 00168 Rome, Italy.
BACKGROUND: A recently devised test of motor cortex excitability (short latency afferent inhibition) was shown to be sensitive to the blockade of muscarinic acetylcholine receptors in healthy subjects. The authors used this test to assess cholinergic transmission in the motor cortex of patients with AD. METHODS: The authors evaluated short latency afferent inhibition in 15 patients with AD and compared the data with those of 12 age-matched healthy controls. RESULTS: Afferent inhibition was reduced in the patients (mean responses +/- SD reduced to 85.7% +/- 15.8% of the test size) compared with controls (mean responses +/- SD reduced to 45.3% +/- 16.2% of the test size; p < 0.001, unpaired t-test). Administration of a single oral dose of rivastigmine improved afferent inhibition in a subgroup of six patients. CONCLUSIONS: The findings suggest that this method can be used as a noninvasive test of cholinergic pathways in AD. Future studies are required to evaluate whether short latency afferent inhibition measurements have any consistent clinical correlates.
PMID: 12177373

Neurosci Lett. 2001 Nov 13;314(1-2):57-60.
Transcranial magnetic stimulation in Alzheimer disease: motor cortex excitability and cognitive severity.
Alagona G, Bella R, Ferri R, Carnemolla A, Pappalardo A, Costanzo E, Pennisi G.
Department of Neurological Sciences, University of, Catania, Italy
To study the possible changes of cortical excitability in the Alzheimer disease (AD) by transcranial magnetic stimulation (TMS) and to evaluate their eventual correlation with its stage twenty-one AD patients and 18 normal controls underwent TMS. Motor threshold, amplitudes of motor evoked potentials (MEPs), central motor conduction time (CMCT) and silent period (SP) were considered. The motor threshold in AD patients was lower than in normal subjects with a significant correlation between the stage of cognitive severity. The amplitude of MEPs was increased and the SP duration was reduced in AD patients. No significant differences were obtained for CMCT. These findings could suggest a correlation between increased motor cortical excitability and cognitive severity. Moreover, the increased cortical excitability could represent a key to understand the mechanism of AD and may have implication for novel treatment strategies.
PMID: 11698146

Brain. 2001 Jun;124(Pt 6):1131-7.
Examination of motor output pathways in patients with corticobasal ganglionic degeneration using transcranial magnetic stimulation.
Valls-Sole J, Tolosa E, Marti MJ, Valldeoriola F, Revilla M, Pastor P, Blesa R.
Unitat d’EMG, Neurology Service, Hospital Clinic, Universitat de Barcelona, Villarroel, 170 Barcelona 08036, Spain.
The alien hand sign (AHS) is often encountered in patients with corticobasal ganglionic degeneration (CBGD), revealing a unilateral dysfunction of the motor system of unknown pathophysiology. We examined the possibility of an abnormal cortical representation of hand muscles in 10 patients with probable CBGD and a prominent AHS. Cortical maps were obtained from the responses to magnetic stimuli applied with a figure of eight coil at an intensity of 110% above motor threshold. For comparison, the same study was carried out in 10 normal volunteers, eight patients with Parkinson’s disease and eight patients with Alzheimer’s disease. AHS patients had a larger extension of the cortical map to stimulation of the hemisphere contralateral to the AHS in comparison with the ipsilateral hemisphere. Furthermore, in six patients, focal stimulation of the hemisphere ipsilateral to the AHS gave rise to ipsilateral responses, delayed by a mean of 7.7 +/- 2.2 ms with respect to those recorded in the same muscle to contralateral stimulation. None of the other patients or control subjects had ipsilateral responses. Our results indicate an enhanced excitability, or reduced inhibition, of the motor area of the hemisphere contralateral to the AHS. The delay of the ipsilateral responses is compatible with a disinhibited transcallosal input.
PMID: 11353729

Dtsch Med Wochenschr. 1999 Dec 23;124(51-52):1577-81.
[Neurology. Therapeutic advances through systems research and molecular biology]
[Article in German]
Hohlfeld R, Brandt T.
Institut fur Klinische Neuroimmunologie, Klinikum Grosshadern, Ludwig Maximilians Universitat, Munchen.
PMID: 10664661

J Neurol Sci. 1999 Nov 30;170(2):119-23.
Motor cortex inhibition is not impaired in patients with Alzheimer’s disease: evidence from paired transcranial magnetic stimulation.
Pepin JL, Bogacz D, de Pasqua V, Delwaide PJ.
University Department of Neurology, CHR Citadelle, Bd du XIIeme de Ligne, 1, 4000, Liege, Belgium.
Motor cortex excitability was studied by transcranial magnetic stimulation (TMS) in 17 patients with Alzheimer’s disease (AD). Resting and active thresholds for TMS were significantly reduced in AD patients compared to young and aged healthy subjects. The maximum amplitude of the motor response evoked by TMS was also significantly increased in AD patients. We have tested if these changes are related to a modification of the short-lasting intracortical inhibition of the motor cortex by paired conditioning-test TMS. We found no significant differences between AD patients and aged healthy subjects even if there is a slight but significant difference between aged and young normal subjects. We conclude that the modification of excitability of the motor cortex does not result from an impaired intracortical inhibition.
PMID: 10561527

J Neurol. 1997 May;244(5):304-7.
Magnetic stimulation in Alzheimer’s disease.
de Carvalho M, de Mendonca A, Miranda PC, Garcia C, Luis ML.
Department of Neurology, Hospital de Santa Maria, Lisbon, Portugal.
Alzheimer’s disease (AD) is a common cause of dementia in which some clinical motor abnormalities have been described. We used transcranial magnetic stimulation in order to test the hypothesis that the change in the motor cortex might cause modifications in motor excitability. Fourteen mildly to moderately affected AD patients were compared with 11 controls matched for age, height and sex. The motor evoked potential threshold value for the relaxed abductor digiti minimi was lower in the AD patients than in the control group for both left and right hemispheres (P < 0.05). No statistically significant difference was found comparing the left and the right hemispheres thresholds in each population. The mean interside threshold differences were small and not significantly different between patients and controls. The spinal motor neuron excitability, as evaluated by F/M and H/M waves amplitude ratios, showed no difference between the groups, reinforcing the motor cortex increased excitability hypothesis to explain this difference. Degeneration of inhibitory gabaergic terminals might be the basis for the increased cortical excitability in the motor cortex of the Alzheimer patients; postsynaptic changes in the GABAA receptors might also affect inhibitory gabaergic transmission. The increased excitability found by transcranial magnetic stimulation in the motor cortex is important for understanding the emergence of seizures and myoclonus in this disease.
PMID: 9178155

J Neurol Sci. 1996 Jan;135(1):31-7.
Evaluation of the motor cortex by magnetic stimulation in patients with Alzheimer disease.
Perretti A, Grossi D, Fragassi N, Lanzillo B, Nolano M, Pisacreta AI, Caruso G, Santoro L.
Department of Clinical Neurophysiology, University of Naples, Italy.
Motor evoked potentials (MEPs) from abductor pollicis brevis (APB) and tibialis anterior (TA) muscles elicited by transcranial magnetic stimulation of the motor cortex were studied in 15 patients with Alzheimer disease (AD). An abnormally higher MEP threshold in APB, frequently associated with absence of the MEP in relaxed TA muscles, was found in 40% of patients, almost all of them in the more severe stage of the disease. The MEP amplitude and averaged MEP/MAP ratio were reduced respectively by 20% and 26% in the APB muscle, and by 46.7% and 53.3% in the TA muscle. The less frequent prolongation of the central conduction time (CCT) (20%) might reflect preservation of the impulse propagation along the surviving pyramidal fibers. In 63.6% of the patients the central silent period (cSP) duration in the APB muscle was shortened; the mean value was significantly different between patients and controls. The results of this study suggest that loss and/or dysfunction of motor cortex neurones, including pyramidal cells and inhibitory interneurones may occur in AD patients before clinical signs become apparent.
PMID: 8926493

-end- Alzheimer’s and repetitive transcranial magnetic stimulation (rTMS) / PEMF bibliography.