Open-label, short-term, repetitive transcranial magnetic stimulation in patients with Alzheimer's disease with functional imaging correlates and literature review

Abstract

Background: Accumulating evidence suggests repetitive transcranial magnetic stimulation (rTMS) may be beneficial in ameliorating cognitive deficits in Alzheimer's disease (AD).

Methods: AD patients received four high-frequency rTMS sessions over the bilateral dorsolateral prefrontal cortex (DLPFC) over two weeks. Structured cognitive assessments were administered at baseline, at 2 weeks after completion of rTMS, and at 4 weeks post treatment. At these same times, tolerant patients underwent functional magnetic resonance imaging (fMRI) while performing structured motor and cognitive tasks. We also reviewed literature regarding the effects of rTMS on cognitive function in AD.

Results: A total of 12 patients were enrolled, eight of whom tolerated the fMRI. Improvement was seen in Boston Diagnostic Aphasia Examination tests of verbal and non-verbal agility 4 weeks post-treatment. The fMRI analysis showed trends for increased activation during cognitive performance tasks immediately after and at 4 weeks post-treatment. Our literature review revealed several double-blind, sham-controlled studies, all showing sustained improvement in cognition of AD patients with rTMS.

Conclusions: There was improvement in aspects of language after four rTMS treatments, sustained a month after treatment cessation. Our results are consistent with other studies and standardization of treatment protocols using functional imaging may be of benefit.

Keywords: Alzheimer’s disease; fMRI; rTMS.

Figure 1.

Left sagittal, coronal, and axial fMRI scans of a single study patient at baseline, post-rTMS, and 4 weeks follow-up while performing action word generation tasks showing increased activation over Broca’s area. Peak t value at (A) 5.7, (B) 11.7, (C) 10.3. fMRI indicates functional magnetic resonance imaging; rTMS, repetitive transcranial magnetic stimulation.