Study on the Effect of Transcranial Magnetic Stimulation in Mild to Moderate Alzheimer's Disease

Prospective, Randomized, Evaluator-blind, Single Center Study on the Effect of Transcranial Magnetic Stimulation in Mild to Moderate Alzheimer's Disease

The investigators will compare cognitition, mood (depression), ADL, and brain structural and functional MRI before and after 4-week transcranial magnetic stimulation in patients with mild to moderate Alzheimer's disease.

The investigators also compare the change of cognitition, mood (depression), ADL, and brain structural and functional MRI between TMS group and sham coil group.

Study Overview

• Status: Unknown
• Conditions: Mild to Moderate Alzheimer Disease
• Intervention / Treatment: Device: TMS; Device: sham coil stimulation

Detailed Description

Each 16 patients will be allocated to TMS group and sham coil group. Before TMS/sham coil stimulation, the investigators will take fMRI of each patient, and figure out which focus has strongest connectivity to hippocampus among lateral parietal regions of the brain. The investigators will fix the TSM transduced and apply accurate TMS stimulation to the focus using personalized frames. The investigators will make the frame using 3D printing technology.

After 4 week- TMS stimulation, the investigators will compare cognitition, mood (depression), ADL, and brain structural and functional MRI beween baseline and after intervention. The investigators also compare the change of cognitition, mood (depression), ADL, and brain structural and functional MRI between TMS group and sham coil group.

• Study Type: Interventional
• Enrollment (Anticipated): 32
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Young Hee Jung, MD PhD; Phone Number: 82-10-6755-5462; Email: neophilia1618@gmail.com
• Study Contact Backup: Name: Sun Young Lee; Phone Number: 82-2-3410-3788; Email: l2sy82@hanmail.net

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center
    • Contact: Sun Young Lee; Phone Number: +82-2-3410-3788; Email: l2sy82@hanmail.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients who visited memory clinic of Samsung Medical Center
• aged 55 ~ 90
• diagnosed as probable Alzheimer dementia according to NIA-AA guideline 2011, or MCI patiens with amyloid PET positivity
• below -1SD in SVLTdelayed recall test and RCFT delayed recall test
• K-MMSE >=18
• no epileptic discharge in EEG
• no history of epilepsy
• no arrhythmia or MI in ECG
• can read and write Korean (literate)
• volunteer and agree to the registration

Exclusion Criteria:

• no other neurologic deficit which can cause dementia except for Alzheimer's disease
• paitient who has severe cerebral white matter hyperintensities. (deep white matter >=2.5cm and caps or band >=1.0 cm)
• patients with severe medical disease including caner and ishemic heart disease
• claustrophobia or allergic to contrast of MRI
• medical deviced which is not removable (e.g pacemaker, cochlear implantation, dental prosthesis)
• history of brain surgery, and intervension or surgery of intra/extracranial artery(e.g. carotid artery stent insertion, CEA)
• patient with dyspnea during resting
• history of loss of consciousness for more than 1 hour except for general anesthesia
• patients who cannot read written material because of poor visual acuity
• patients who cannot communicate because of severe hearing difficulty
• history of ototoxicity medication or exposure severe noises
• determined as inapropriate to participate clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: TMS group; Transcranial magnetic stimulation for four weeks	Device: TMS; stimulation intensity : motor threshold 100%; stimulation frequency : 1600 pulses for 20 minutes; stimulation duration :for four weaks, 20 minutes/day, 5 days per week (Monday - Friday )
Sham Comparator: Sham group; sham coil stimulation for four weeks (Although the sound of sham coil is the same to that of real TMS during intervension, no stimulation is applied. )	Device: sham coil stimulation; no stimulation Although the sound from device during stimulation is similar, no stimulation is applied.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the short term change of K-MMSE score in TMS group	the short term change of K-MMSE (Korean version of mini mental status exam) score in TMS group	4 weeks
the short term change of K-MoCA score in TMS group	the short term change of K-MoCA (Korean version of Montreal cognitive assessment) score in TMS group	4 weeks
the short term change of ADAS-Cog score in TMS group	the short term change of ADAS-Cog(the Alzheimer's disease assessment scale-cognitive subscale) score in TMS group	4 weeks
the short term change of COWAT score in TMS group	the short term change of COWAT(controlled oral word association) score in TMS group	4 weeks
the short term change of Stroop score in TMS group	the short term change of Stroop score in TMS group	4 weeks
the short term change of TMT score in TMS group	the short term change of TMT(trail-making test) score in TMS group	4 weeks
the short term change of RVP score in TMS group	the short term change of RVP(raid visual information processing) score in TMS group	4 weeks
the short term change of SWM score in TMS group	the short term change of SWM (spatial working memory) score in TMS group	4 weeks
the short term change of PRM score in TMS group	the short term change of PRM(pattern recognition memory) score in TMS group	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the long term change of K-MMSE score in TMS group	the long term change of K-MMSE (Korean version of mini mental status exam) score in TMS group	8 weeks
the long term change of K-MoCA score in TMS group	the long term change of K-MoCA (Korean version of Montreal cognitive assessment) score in TMS group	8 weeks
the long term change of ADAS-Cog score in TMS group	the long term change of ADAS-Cog(the Alzheimer's disease assessment scale-cognitive subscale) score in TMS group	8 weeks
the long term change of COWAT score in TMS group	the long term change of COWAT(controlled oral word association) score in TMS group	8 weeks
the long term change of Stroop score in TMS group	the long term change of Stroop score in TMS group	8 weeks
the long term change of TMT score in TMS group	the long term change of TMT(trail-making test) score in TMS group	8 weeks
the long term change of RVP score in TMS group	the long term change of RVP(raid visual information processing) score in TMS group	8 weeks
the long term change of SWM score in TMS group	the long term change of SWM (spatial working memory) score in TMS group	8 weeks
the long term change of PRM score in TMS	the long term change of PRM(pattern recognition memory) score in TMS group	8 weeks
the change of ADL(activity of daily life) in TMS group	the score change of S-IADL(Seoul-Instrumental activities of daily life)	4 weeks
the short term change of mood (depression) in TMS group	the score change of GDS(geriatric depression scale) short form	4 weeks
the long term change of mood (depression) in TMS group	the score change of GDS(geriatric depression scale) short form	8 weeks
the change of brain function in TMS group	the qualititve change of resting functional MRI	4 weeks
the change of brain structure in TMS group	the change of FA (fractional anisotropy) value in DTI (diffusion tensor imaging) analysis	4 weeks
the comparison of short term change of K-MMSE score between TMS group and sham group	the score change of K-MMSE (Korean version of mini mental status exam)	4 weeks
the comparison of short term change of K-MoCA score between TMS group and sham group	the score change of K-MoCA (Korean version of Montreal cognitive assessment)	4 weeks
the comparison of short term change of CDR-SOB between TMS group and sham group	the score change of CDR-SOB (Clinical dementia rating-sum of boxes)	4 weeks
the comparison of short term change of ADAS-Cog between TMS group and sham group	the score change of ADAS-Cog ( the Alzheimer's disease assessment scale-cognitive subscale)	4 weeks
the comparison of short term change of COWAT score between TMS group and sham group	the score change of COWAT(controlled oral word association) score	4 weeks
the comparison of short term change of Stroop test score between TMS group and sham group	the score change of Stroop test score	4 weeks
the comparison of short term change of TMT between TMS group and sham group	the score change of TMT (trail making test)	4 weeks
the comparison of short term change of RVP score between TMS group and sham group	the score change of RVP(raid visual information processing) score	4 weeks
the comparison of short term change of SWM between TMS group and sham group	the score change of SWM (spatial working memory) score	4 weeks
the comparison of short term change of PRM between TMS group and sham group	the score change of PRM(pattern recognition memory) score	4 weeks
the comparison of change of K-MMSE between TMS group and sham group	the score change of K-MMSE(Korean version of mini mental status exam)	8 weeks
the comparison of long term change of K-MoCA between TMS group and sham group	the score change of K-MoCA (Korean version of Montreal cognitive assessment)	8 weeks
the comparison of long term change of CDR-SOB between TMS group and sham group	the score change of CDR-SOB(Clinical dementia rating-sum of boxes)	8 weeks
the comparison of long term change of ADAS-Cog between TMS group and sham group	the score change of ADAS-Cog ( the Alzheimer's disease assessment scale-cognitive subscale)	8 weeks
the comparison of long term change of COWAT score between TMS group and sham group	the score change of COWAT(controlled oral word association) score	8 weeks
the comparison of long term change of stroop test score between TMS group and sham group	the score change of stroop test score	8 weeks
the comparison of long term change of TMT score between TMS group and sham group	the score change of TMT(trail making test)	8 weeks
the comparison of long term change of RVP score between TMS group and sham group	the score change of RVP(raid visual information processing)	8 weeks
the comparison of long term change of SWM score between TMS group and sham group	the score change of SWM (spatial working memory) score	8 weeks
the comparison of long term change of cognitive function between TMS group and sham group	the score change of PRM(pattern recognition memory) score	8 weeks
the comparison of short term change of mood (depression) between TMS group and sham group	the score change of GDS (geriatric depression scale) short form	4 weeks
the comparison of long term change of mood (depression) between TMS group and sham group	the score change of GDS (geriatric depression scale) short form	8 weeks
the comparison of short term change of ADL between TMS group and sham group	the score change of S-IADL(Seoul instrumental activity of daily life )	4 weeks
the comparison of long term change of ADL between TMS group and sham group	the score change of S-IADL(Seoul instrumental activity of daily life )	8 weeks
the comparison of change of resting fMRI between TMS group and sham group	the qualititve change of resting fMRI	4 weeks
the comparison of change of FA value between TMS group and sham group	the change of FA(fractional anisotropy) value in DTI(diffusion tensor imaging) analysis	4 weeks

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Investigators: Principal Investigator: Duk L Na, MD PhD, Samsung Medical Center

Publications and helpful links

General Publications

• Cotelli M, Calabria M, Manenti R, Rosini S, Zanetti O, Cappa SF, Miniussi C. Improved language performance in Alzheimer disease following brain stimulation. J Neurol Neurosurg Psychiatry. 2011 Jul;82(7):794-7. doi: 10.1136/jnnp.2009.197848. Epub 2010 Jun 23.
• Cotelli M, Manenti R, Cappa SF, Geroldi C, Zanetti O, Rossini PM, Miniussi C. Effect of transcranial magnetic stimulation on action naming in patients with Alzheimer disease. Arch Neurol. 2006 Nov;63(11):1602-4. doi: 10.1001/archneur.63.11.1602.
• Koch G, Bonni S, Pellicciari MC, Casula EP, Mancini M, Esposito R, Ponzo V, Picazio S, Di Lorenzo F, Serra L, Motta C, Maiella M, Marra C, Cercignani M, Martorana A, Caltagirone C, Bozzali M. Transcranial magnetic stimulation of the precuneus enhances memory and neural activity in prodromal Alzheimer's disease. Neuroimage. 2018 Apr 1;169:302-311. doi: 10.1016/j.neuroimage.2017.12.048. Epub 2017 Dec 19.
• Wang JX, Rogers LM, Gross EZ, Ryals AJ, Dokucu ME, Brandstatt KL, Hermiller MS, Voss JL. Targeted enhancement of cortical-hippocampal brain networks and associative memory. Science. 2014 Aug 29;345(6200):1054-7. doi: 10.1126/science.1252900.
• Cotelli M, Manenti R, Cappa SF, Zanetti O, Miniussi C. Transcranial magnetic stimulation improves naming in Alzheimer disease patients at different stages of cognitive decline. Eur J Neurol. 2008 Dec;15(12):1286-92. doi: 10.1111/j.1468-1331.2008.02202.x.
• Nilakantan AS, Mesulam MM, Weintraub S, Karp EL, VanHaerents S, Voss JL. Network-targeted stimulation engages neurobehavioral hallmarks of age-related memory decline. Neurology. 2019 May 14;92(20):e2349-e2354. doi: 10.1212/WNL.0000000000007502. Epub 2019 Apr 17.
• Ridding MC, Rothwell JC. Is there a future for therapeutic use of transcranial magnetic stimulation? Nat Rev Neurosci. 2007 Jul;8(7):559-67. doi: 10.1038/nrn2169.
• Bondi MW, Edmonds EC, Jak AJ, Clark LR, Delano-Wood L, McDonald CR, Nation DA, Libon DJ, Au R, Galasko D, Salmon DP. Neuropsychological criteria for mild cognitive impairment improves diagnostic precision, biomarker associations, and progression rates. J Alzheimers Dis. 2014;42(1):275-89. doi: 10.3233/JAD-140276.
• Weissman MM, Myers JK, Tischler GL, Holzer CE 3rd, Leaf PJ, Orvaschel H, Brody JA. Psychiatric disorders (DSM-III) and cognitive impairment among the elderly in a U.S. urban community. Acta Psychiatr Scand. 1985 Apr;71(4):366-79. doi: 10.1111/j.1600-0447.1985.tb02536.x.
• Kim S, Nilakantan AS, Hermiller MS, Palumbo RT, VanHaerents S, Voss JL. Selective and coherent activity increases due to stimulation indicate functional distinctions between episodic memory networks. Sci Adv. 2018 Aug 22;4(8):eaar2768. doi: 10.1126/sciadv.aar2768. eCollection 2018 Aug.

Study record dates

Study Major Dates

• Study Start (Anticipated): February 7, 2020
• Primary Completion (Anticipated): February 7, 2021
• Study Completion (Anticipated): February 7, 2022

Study Registration Dates

• First Submitted: January 22, 2020
• First Submitted That Met QC Criteria: February 5, 2020
• First Posted (Actual): February 7, 2020

Study Record Updates

• Last Update Posted (Actual): February 7, 2020
• Last Update Submitted That Met QC Criteria: February 5, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: SMC_2019-04-010-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No