It is quite interesting that stimulation of the fornix/hypothalamus influences memory, with notable effects on FDG-PET activity in the regions of abnormality in AD. With the success of DBS for Parkinson's, this approach is clearly feasible. Of course, much more work is required to determine whether DBS can produce clinically meaningful benefits in AD, mild cognitive impairment, or other amnestic disorders. But Andres Lozano and his colleagues should be applauded for this novel and intriguing approach.

View all comments by Paul Aisen

I have studied Alzheimer disease (AD) since 1978, and since about 1980, I have seen some new ideas for treating AD nearly every month. Of these, five have been FDA approved and have modest benefits for patients (some improvement in cognition and behavior, and changing the course of the disease by a few months). I am sure that 300 good ideas have failed in this time, and there is nothing on the horizon that looks like it will stop AD.

This study of brain stimulation does not distinguish itself from other failed approaches at this point. The rationale for how this treatment would stop the development of senile plaques and neurofibrillary tangles is missing. The idea of stimulating the "default mode network" is also weak. The idea of stimulating the fornix is admirable, but I think it is a little too much wishful thinking to really conceive that this would help to stop Alzheimer pathology or improve memory in a dementia patient. If this approach could be shown to diminish amyloid deposition in the brain (even in a few locations), lower CSF tau, and show long-term improvement or...  Read more

I have studied Alzheimer disease (AD) since 1978, and since about 1980, I have seen some new ideas for treating AD nearly every month. Of these, five have been FDA approved and have modest benefits for patients (some improvement in cognition and behavior, and changing the course of the disease by a few months). I am sure that 300 good ideas have failed in this time, and there is nothing on the horizon that looks like it will stop AD.

This study of brain stimulation does not distinguish itself from other failed approaches at this point. The rationale for how this treatment would stop the development of senile plaques and neurofibrillary tangles is missing. The idea of stimulating the "default mode network" is also weak. The idea of stimulating the fornix is admirable, but I think it is a little too much wishful thinking to really conceive that this would help to stop Alzheimer pathology or improve memory in a dementia patient. If this approach could be shown to diminish amyloid deposition in the brain (even in a few locations), lower CSF tau, and show long-term improvement or even maintenance of cognitive and behavioral function, then it could be a tremendous advance.

There is a problem with the results of this study. The presented results do not show any clear benefit, and there is little attempt to correct the effects of the stimulation on the ADAS and MMSE for severity and age. These are important factors that need to be addressed. Evidence of beneficial effect on relevant biomarkers is becoming more important for accepting therapeutic interventions, and long-term demonstrations of clinical improvement, with careful control for specific ApoE genotypes, are also needed.

In summary, I think it was good that this study was done, but it remains to be seen whether it will have promise for the future.

View all comments by John (Wes) Ashford

I think the trial is too short (two years) to address the most important caveat: the loss of DBS efficacy over time. Hence, the trial is not well conceived, in my opinion.

Another issue is that the actual rationale for DBS use—as the authors themselves state in the introduction—is to deal with serious dyskinetic side effects that develop with extended use of pharmacological therapies.

Given that DBS is not a restorative treatment—such as replacing or restoring the original neurons—this effort may drive up the use of this technology to new patient groups who are less likely to benefit from this treatment over a decade than they might from pharmacological or other therapies. And DBS brings significant risks for complications. The use of DBS, and the risks associated with the implantation and the non-physiological electrical stimulation on diverse neural brain circuitries are not known.

View all comments by Ole Isacson