Transcranial Magnetic Stimulation Improves Certain Language Deficits in Alzheimer's Disease

Pauline Anderson

June 29, 2010

June 29, 2010 — Patients with Alzheimer's disease (AD) who received repetitive transcranial magnetic stimulation (rTMS) to the prefrontal cortex experienced improved auditory sentence comprehension, results of a new study suggest. The improvement was apparent after 2 weeks and persisted for 8 weeks.

"Our findings provide initial evidence for the persistent beneficial effects of rTMS on sentence comprehension in AD patients," said lead author Maria Cotelli, PhD, from the IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy, in an email. "Rhythmic rTMS, in conjunction with other therapeutic interventions, may represent a novel approach to the treatment of language dysfunction in AD patients."

The study was published online June 23 in the Journal of Neurology, Neurosurgery & Psychiatry.

Rapid Pulses

In addition to memory, AD affects language and several other cognitive functions, the authors note.

This study included 10 outpatients diagnosed with probable moderate AD, all of whom had been on a stable dose of a cholinesterase inhibitor for at least 6 months. Patients were randomly assigned to receive 4 weeks of rTMS of the left dorsolateral prefrontal cortex (DLPFC) or to receive placebo stimulation for 2 weeks, followed by 2 weeks of real stimulation.

TMS, which delivers pulses in rapid sequence up to frequencies of 100 Hz, can modulate neuronal activity with effects depending on the stimulation frequency. In this study, patients received 5 daily sessions of 25 minutes each per week. During each session, trains of rhythmic high-frequency rTMS were delivered in short periods separated by longer periods of no stimulation. The total number of pulses for each session was 2000.

All participants tolerated rTMS well and did not report any adverse effects.

Researchers screened the patients for dementia and performed neuropsychological tests for memory, executive function, and language.

Patients in the real rTMS group improved their performance in tests of auditory sentence comprehension (P = .008), a subtest from the Battery for Analysis of Aphasic Deficits, after the first 2-week phase (77.3) compared with baseline scores (66.6). There was no significant difference (P = .99) in the placebo group between baseline (66.0) and 2 weeks of sham treatment (65.9).

There were no rTMS effects on memory or executive function, suggesting that the effect of DLPFC in AD is specific to the language domain.

Continuing the treatment for an additional 2 weeks did not result in additional improvements in performance. "Our results suggest that 2 weeks of rTMS is...sufficient to evidence behavioral improvements in AD patients," the authors write.

Long-Lasting Effect

The researchers identified an improvement in sentence comprehension 8 weeks after the end of any rTMS intervention. "To date, this is the first study that shows a long lasting cognitive effect of rTMS treatment in AD patients," said the authors.

Age and education level did not significantly change the findings, said Dr. Cotelli.

Although the exact neurophysiological mechanism affecting this cognitive function is unknown, it is possible that the modification of cortical activity through rhythmic stimulation may readjust pathological patterns of brain activity, said Dr. Cotelli. "This may provide an opportunity to induce new, healthier, activity patterns within the affected functional networks."

Although the current study suggests that stimulating the prefrontal cortex affects the language domain, further investigation could determine whether stimulation of other cortical areas would improve other cognitive abilities, said Dr. Cotelli.

These preliminary results highlight the therapeutic potential of brain stimulation, she said. "They hold considerable promise not only for advancing our understanding of brain plasticity mechanisms but also for designing new rehabilitation strategies in patients with neurodegenerative disease."

Such new strategies could include combining brain stimulation with standard cognitive rehabilitation procedures, which might increase the effect of either approach separately, added Dr. Cotelli.

"We predict that the use of brain stimulation techniques in combination with specific behavioral training could provide the exciting possibility to induce behavioral improvements in patients with cognitive deficits," the authors conclude. "It is likely that brain stimulation might interact with the intrinsic ability of the brain to restore damaged functions, by increasing the recruitment of compensatory functional networks and the plasticity of the system."

Exciting Possibility

Reached for a comment, Catherine M. Roe, PhD, assistant professor of neurology, Washington University School of Medicine, St. Louis, Missouri, said she found the study results "fascinating," although it will take a long time before rTMS is "ready to be rolled out into a treatment."

Magnetic stimulation does make sense, she said. "If you think about it, the brain is a bunch of electrical signals, so if you change the electrical signals, I could definitely see changing some kind of behavior."

However, it is not clear whether the changes detected in tests of sentence comprehension would translate into real-life improvements, she said. "If this were to be a treatment, it would be important to eventually show that it translates into better comprehension and interaction with other people in your world."

Dr. Roe added she would have liked the study to include a third group that got sham stimulation for the entire study for comparison.

The research was supported by a project grant from the Ministero della Sanita and from the Associazione Fatebenefratelli per la Ricerca. The authors have disclosed no relevant financial relationships.

J Neurol Neurosurg Psychiatry. Published online June 23, 2010.

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