DBS Update: Attempting to Stimulate Memory in Alzheimer’s

Researchers are sliding electrodes into the brains of people with Alzheimer disease, hoping to awaken memories and stave off disease-induced forgetfulness. In the August 4 Annals of Neurology online, a team led by Andres Lozano at Toronto Western Hospital report on a small deep-brain stimulation (DBS) trial. They write that the therapy was safe and was able to alter brain metabolism.

DBS can quell the symptoms of Parkinson disease and is under investigation for a variety of conditions, including Huntington disease, pain, epilepsy, and Tourette syndrome (see ARF four-part news story on advances in this treatment technique). Lozano and colleagues first discovered its effect on memory when they stimulated the hypothalamus of an obese man. They were hoping to curb his appetite, but instead induced a flashback to a 30-year-old memory (Hamani et al., 2008).

Now, Lozano, first author Adrian Laxton, and colleagues have completed a Phase 1 trial on six participants with early Alzheimer’s. The physicians were successful in their primary goal—to show the treatment is safe—as none of the six suffered serious adverse effects.

Further, the scientists looked for evidence that the stimulation was increasing brain activity. Alzheimer disease dampens glucose metabolism in the temporal and parietal regions, so Laxton and the other researchers used positron emission tomography (PET) to examine metabolism after DBS. Changes occurred within one month of starting stimulation, with metabolism going up in both the temporal and parietal areas.

The researchers also examined the subjects for evidence of altered cognition. Standard measures such as the Mini-Mental State Examination (MMSE) and the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-cog) do not decrease linearly or regularly, so it is difficult to speculate how much decline the participants would have experienced without DBS. With no placebo control participants for comparison, the study was not able to clearly demonstrate cognitive effects. The researchers suggest that a few participants seemed to benefit, though, in that their scores improved or declined more slowly than might be expected.

Lozano and colleagues, satisfied with their results, are now planning a multicenter Phase 2 trial. The technique is currently approved by the FDA for Parkinson disease, essential tremor, and dystonia.

Laxton AW, Tang-Wai DF, McAndrews MP, Zumsteg D, Wennberg R, Keren R, Wherrett J, Naglie G, Hamani C, Smith GS, Lozano AM. A Phase I trial of deep brain stimulation of memory circuits in Alzheimer’s disease. Ann Neurol. 2010 Aug 4. Abstract

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