DBS May Slow Cognitive Decline in Alzheimer’s Disease

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Can deep brain stimulation slow the decline of Alzheimer’s disease? Some new research may be pointing to Yes!

In clinical trials the same results are now being seen for the secondary clinical measures.

However, in a post hoc subgroup analysis, older patients appeared to derive some benefit from DBS, with those in the active, or “on,” stimulation group showing less decline in both ADAS-Cog 13 and CDR-SB scores.

The difference in worsening of ADAS-Cog-13 scores in patients aged 65 years and older who received stimulation vs those who received no stimulation was 4.5 + 2.0 points at 9 months and 4.1 + 2.6 at 12 months.

A similar benefit was observed in the CDR-SB scores in older patients.

A similar trend for benefit for older patients was seen with regard to FDG-PET for glucose metabolism. Patients younger than 65 years showed a decrease in metabolism while both “on” and “off” stimulation, whereas patients aged 65 years and older showed increased metabolism while “on” stimulation that was 14% to 20% greater than that observed in the group as a whole at 6 and 12 months.

“This was an exploratory study, so we didn’t have a fixed number of patients and a set hypothesis we were testing. It was to see whether there might be some patients who might respond,” said Dr Lozano.

He explained how increasing glucose metabolism could be of benefit to patients with AD.

“These areas of the brain are underperforming. It’s as if the lights are dim in some areas of the brain. They are shut down. We are trying to turn them back on. We think that the symptoms come because these circuits are underperforming, so we would like to boost the activity of these circuits using electricity to see if that, in turn, restores the cognitive function of patients,” Dr Lozano said.

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Interesting, Intriguing

Commenting on the findings for Medscape Medical News, Gregory A. Jicha, MD, PhD, professor of neurology, Alzheimer’s Disease Center, University of Kentucky, in Lexington, described the study as “interesting.”

“I was exposed to it very early on in the development process, when [the investigators] were treating a woman for an overeating disorder, and as they were aiming for the part of the brain that controls appetite, they missed by a little bit and got close to the fornix, and what happened was her memory became close to photographic with the stimulator there.

“That really intrigued them and got them to think that the DBS stimulating that fornix is going to turn on the memory circuits that are turning down in Alzheimer’s disease, in much the same way we use DBS to turn back on motor circuits that are shutting down in Parkinson’s disease.”

Dr Jicha noted that he found the FDG-PET data that show increased metabolic activity “intriguing.”

“We know that the health of nerve cells is critically dependent on their activity, and the fact that they were able to show in the older subjects effects that persisted to 1 year is intriguing. That raises interest in determining how stimulating one area of the brain can have very distant effects on other areas of the brain, something that’s not really been looked at in Parkinson’s disease per se,” he said.

The study raises important questions, Dr Jicha added.

“For one, why do the elderly appear to benefit while younger Alzheimer’s disease patients do not appear to benefit from DBS? The researchers say they feel that the elderly may have a less aggressive form of disease. That still needs to be determined, especially since their study population was really a mild disease population.

“Also, there was a very small number of subjects. So is that finding a fluke? Is the negative effect seen in the younger folks a real effect or is the post hoc positive effect in the older individuals really what the effect will turn out to be when larger populations are studied?

“I think that they’ve raised some interesting points, but clearly we haven’t definitively proven that deep brain stimulation either is beneficial or is not beneficial on the basis of the results of this study. We’re left with that lingering question. This appears to be a safe way to approach the disease, but we always watch for post hoc analyses because the study was not designed for that.”

The study was supported by the National Institute on Aging, the Federal Economic Development Agency for Southern Ontario, and Functional Neuromodulation Ltd. The authors’ financial relationships with industry are listed in the original article. Dr Jicha has disclosed no relevant financial relationships.


Source:

http://www.medscape.com/viewarticle/866489#vp_2