Effect of Repetitive Transcranial Magnetic Stimulation on Language in Alzheimer's Disease
Condition: Alzheimer's Disease; Aphasia; Dementia
MeSH terms: Alzheimer Disease; Aphasia
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      Subjects for this study will be recruited from Dr. Devi's clinical practice. Eligible
      subjects must have a diagnosis of possible or probable Alzheimer's disease using NINCDS-ADRDA
      criteria. The patient and his or her legally authorized representative need to be available
      to sign the informed consent. The assent of the incapable subject will be obtained prior to
      enrolling the subject in the study.

      Once informed consent and assent are obtained, the subject will have a functional magnetic
      resonance imaging (fMRI) scan of their brain anytime during the 2 weeks prior to the first
      study visit. At Visit 1, subjects will undergo a baseline battery of cognitive tests lasting
      approximately 30 minutes. Subsequently, the subject will undergo rTMS.

      During the visit, Dr. Devi will locate the area of the brain to be stimulated and mark that
      area of the scalp with an indelible skin marker that will wash out over time. In addition,
      the subjects will be provided with ear plugs to use during stimulation. This process of
      locating the area to be stimulated will take about an hour and will occur once. Then rTMS
      will be started and this procedure will take approximately 20-30 minutes (please see the full
      protocol for a complete description of this process).

      Each rTMS stimulation session will last for about 30 minutes, 2 consecutive days a week for 2
      weeks. Both immediately prior to the onset of the first rTMS session, and just after the end
      of the fourth and final rTMS session, subjects will be tested on their cognitive and language
      skills. These two testing sessions will last 30 minutes each. Subjects will have another fMRI
      scan anytime during the 2 days after the fourth and final rTMS stimulation session.

      Subjects will continue to receive usual care throughout the study period. Any changes to
      usual treatment will be noted in the study file.

      All subjects will be seen again 4 weeks after the final study treatment session and will once
      again undergo the brief cognitive battery and fMRI scan.

      The investigators expect to recruit two subjects at a time for the study and each subject
      will be enrolled for 5 weeks from the baseline visit.
    

Intervention name(s): Repetitive Transcranial Magnetic Coil Stimulation (rTMS)
Intervention type(s): Device
Intervention description(s): 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.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Alzheimer; Language; Treatment; TMS; rTMS