Effect of Repetitive Transcranial Magnetic Stimulation on Language in Alzheimer's Disease

NCT00814697 | Completed Phase 2 Results

• 1 other identifier: 91913-5
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators wish to investigate the efficacy of targeted repetitive transcranial magnetic stimulation (rTMS) on expressive language in patients with Alzheimer's disease (AD). In rTMS, magnetic pulses are used to noninvasively stimulate focal areas of cortex of about a square centimeter in area. rTMS has been approved in the United States for the diagnosis of peripheral nerve conditions. Depending on the frequency of stimulation, rTMS can preferentially stimulate or inhibit cortical areas. In stroke rehabilitation, for example, inhibition of the contralateral, uninvolved hemisphere by low frequency rTMS has improved movement of the affected limbs because of less aberrant inhibition of the affected hemisphere by the healthy hemisphere. The effects of rTMS has also been investigated and found to be useful in treating refractory depression and depression in Parkinson's disease. In addition, rTMS has improved naming in patients with Alzheimer's disease and has improved cognitive abilities and memory in non-demented older adults. Two studies found that rTMS improved aphasia in patients with stroke. While these studies are small, a review of the literature suggests that there may be a beneficial role for rTMS in patients with chronic neurological conditions. In addition, rTMS appears to be well tolerated, with transient headaches being the most common side effect. In this small open label study, the investigators wish to investigate the usefulness of bilateral stimulation of the brain region termed the dorsolateral prefrontal cortex (DLPFC) in patients with AD who have naming and language deficits.

Conditions

Alzheimer's Disease; Aphasia; Dementia

Keywords

Alzheimer; Language; Treatment; TMS; rTMS

Outcome Measures

Primary Outcomes (1)

• Cognitive Assessment Task Scores Before, During and After rTMS.

  Cognitive assessment tasks - Boston Diagnostic Aphasia Examination (BDAE), CFL Category naming (CFL), Mini-Mental State Examination (MMSE) - were administered and scored according to standard procedures before, during and 4 weeks after rTMS. Higher scores are associated with better cognition; No absolute cut-offs were used here as the outcomes were not categorically assessed. Total possible score ranges by test, lowest to highest: BDAE - 0 to 15 CFL - 0 to 62 MMSE - 0 to 30 Full range data and means presented below represents range of scores at 4-weeks post-rTMS treatments.

  6 weeks

Study Arms (1)

Transcranial Magnetic Stimulation

EXPERIMENTAL

Repetitive Transcranial Magnetic Coil Stimulation (rTMS) treatment in Alzheimer's disease. The Magstim Rapid2 stimulator with a peak magnetic field of 0.5-3.5 Tesla at 100% output was used over the right and left dorsolateral prefrontal cortex. Patients received 4 sessions of rTMS over 2 weeks, lasting approximately 30 minutes, 2 consecutive days a week for 2 weeks.

Device: Repetitive Transcranial Magnetic Coil Stimulation (rTMS)

Interventions

Repetitive Transcranial Magnetic Coil Stimulation (rTMS) DEVICE

The first six patients were administered rTMS at 10Hz in 20 trains of 5 seconds with 20 second intervals between trains in each hemisphere. The total number of pulses for each session was set at 1000 pulses. The second six enrolled patients were administered rTMS at 15 Hz in 20 trains of 5 seconds with 25 second intervals between trains in each hemisphere.

Transcranial Magnetic Stimulation

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have a diagnosis of probable or possible Alzheimer's disease, diagnosed using standardized criteria.
• If subjects are determined by the PI to lack decisional capacity to consent to the study, a legally authorized representative must be available to sign the informed consent on behalf of the subject. In this case the assent of each subject will be obtained as well. If at any time the subject withdraws his or her assent, the subject will be disenrolled from the study.
• Subjects will score at or below 30 on the 60 item naming section of the Boston Diagnostic Aphasia and/or below 50% on the Controlled Word Association (CFL) Category Naming.

You may not qualify if:

• Subjects newly diagnosed with AD and not yet receiving usual care are not eligible.
• Subjects must not have pacemakers.
• They must not have a history of implanted metal objects.
• They must not have a history of seizures or epilepsy.
• There must not be any recent history of migraines.
• There must not be any history of uncontrolled depression.
• They must not be on any medications that will significantly lower the seizure threshold.
• Any other medical condition that is judged by the PI to make rTMS unsafe for the subject.

Sponsors & Collaborators

• The New York Memory Services: lead

Study Sites (1)

The NY Memory Services

New York, New York, 10021, United States

Location

Related Publications (6)

• 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.

  PMID: 17101829 BACKGROUND

• Ahmed MA, Darwish ES, Khedr EM, El Serogy YM, Ali AM. Effects of low versus high frequencies of repetitive transcranial magnetic stimulation on cognitive function and cortical excitability in Alzheimer's dementia. J Neurol. 2012 Jan;259(1):83-92. doi: 10.1007/s00415-011-6128-4. Epub 2011 Jun 14.

  PMID: 21671144 BACKGROUND

• Bentwich J, Dobronevsky E, Aichenbaum S, Shorer R, Peretz R, Khaigrekht M, Marton RG, Rabey JM. Beneficial effect of repetitive transcranial magnetic stimulation combined with cognitive training for the treatment of Alzheimer's disease: a proof of concept study. J Neural Transm (Vienna). 2011 Mar;118(3):463-71. doi: 10.1007/s00702-010-0578-1. Epub 2011 Jan 19.

  PMID: 21246222 BACKGROUND

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

  PMID: 23076723 BACKGROUND

• 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.

  PMID: 19049544 BACKGROUND

• 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.

  PMID: 20574108 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease; Aphasia; Dementia; Language

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Speech Disorders; Language Disorders; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Communication; Behavior

Results Point of Contact

• Title: Dr. Gayatri Devi
• Organization: The NY Memory and Healthy Aging Services

gd@nymemory.org

212-517-6881

Study Officials

• Gayatri Devi, MD

  The New York Memory Services

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Associate Professor of Neurology & Psychiatry

Study Record Dates

• First Submitted: December 24, 2008
• First Posted: December 25, 2008
• Study Start: December 1, 2008
• Primary Completion: December 1, 2011
• Study Completion: August 1, 2012
• Last Updated: January 28, 2014
• Results First Posted: January 28, 2014

Record last verified: 2014-01

Locations

US (1)