Brain stimulation could help treat Alzheimer’s disease

Summary: Deep brain stimulation at the intersection of two fiber bundles linked to memory formation appears to alleviate symptoms of Alzheimer’s disease.

Source: charity

Alzheimer’s disease is the most common cause of dementia, but it is not easily treatable. One potential therapy is deep brain stimulation delivered by some kind of pacemaker.

A team of researchers from Charité – Universitätsmedizin Berlin has discovered that stimulating a specific network in the brains of patients with Alzheimer’s disease reduces their symptoms.

The researchers hope that the results, which appear in Nature Communicationpave the way for further studies.

Deep brain stimulation (DBS) is a form of therapy already approved in Germany for the treatment of neurological movement disorders such as Parkinson’s disease and dystonia, and neuropsychiatric diseases such as obsessive-compulsive disorder. Very fine electrodes are implanted in the patient’s brain and constantly deliver mild electrical impulses to a specific region.

The electrodes remain permanently in the brain and are connected via wires that run under the skin to a pacemaker-like device implanted in the chest area. The device is used to adjust the strength and frequency of electrical stimulation.

“Although DBS has been an established treatment for Parkinson’s disease for a good 20 years now, and the costs are covered by health insurance funds, it is still not a widely known therapy,” says Professor Andreas Horn, head of a lab exploring network-based brain stimulation in the Department of Neurology and Experimental Neurology at Campus Charité Mitte, as well as Brigham and Women’s Hospital and Massachusetts General Hospital, both affiliated with Harvard Medical School in Boston, USA.

“DBS works very well in patients with Parkinson’s disease,” he says. “It dramatically improves their quality of life.”

Since Alzheimer’s disease is also a neurodegenerative disease, it seems likely that DBS could be used to treat this disease as well. But safe and effective treatment is only possible if the precise brain regions that require stimulation are known.

The starting point for the current study, which the researchers conducted in close collaboration with multiple partners, including the University of Toronto in Canada, was a random observation made as part of a Canadian study.

“In one patient, who was being treated for obesity, deep brain stimulation elicited flashbacks – sudden memories of childhood and adolescence,” says Dr. Ana Sofía Ríos from the Department of Neurology and Experimental Neurology at Campus Charité Mitte, and study lead author.

“This led Canadian researchers to suspect that stimulation of this region of the brain, located in the fornix, might also be suitable for the treatment of Alzheimer’s disease.”

To investigate this question further, researchers working at seven international centers in a multicenter study implanted electrodes in the same area of ​​the fornix in participants with mild Alzheimer’s disease.

“Unfortunately, most patients showed no improvement in their symptoms. But a handful of participants benefited significantly from the treatment,” says Dr. Ríos.

“In the current study, we wanted to find the root cause of these differences, so we compared the exact position of the electrodes in each participant.”

Professor Horn’s research group specializes in analyzing high-resolution magnetic resonance images of the brain and combining them with computer models to accurately identify optimal locations for DBS.

“One of the main challenges is that every brain is different – and that’s really important for accurately planting the electrodes,” says Professor Horn.

“When the electrodes are placed even a few millimeters from the target, it can result in a lack of patient benefit.”

This shows a brain slice with highlighted areas
In people with Alzheimer’s disease, the greatest positive effect was observed when stimulating the region between the fornix (green) and the bed nucleus of the stria terminalis (blue). Also shown are two brain structures – the thalamus (pink) and the hippocampus (yellow) – as well as the stimulation electrodes. Credit: Charity | Ana Sofia Rios

This is what happened for most of the study participants. But Professor Horn and his team were able to use the imaging data to determine the exact position of the electrodes in patients who had the procedure.

“The optimal site of stimulation appears to be the intersection of two bundles of fibers – the fornix and the stria terminalis – which connect deep regions of the brain. Both structures have been linked to memory function,” says Professor Horn.

More clinical studies are needed before DBS can be approved and used to treat Alzheimer’s disease. The current results are an important next step in the process.

“If our data allows more precise placement of electrodes in neurosurgical studies testing DBS in patients with Alzheimer’s disease, that would be fantastic,” says Professor Horn.

“We desperately need an effective therapy that alleviates the symptoms of this disease – and DBS shows great promise.”

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Going forward, the Horn lab will conduct further studies to investigate and define other neural networks in the brain that may be useful in the treatment of dementia. Their work will include examining areas of brain damage and identifying target regions for DBS and other neurostimulation methods.

About this Alzheimer’s disease research news

Author: Manuela Zingl
Source: charity
Contact: Manuela Zingl – Charity
Image: Image is credited to Charity | Ana Sofia Rios

Original research: Free access.
Optimal stimulation sites and networks for deep brain stimulation of the fornix in Alzheimer’s disease” by Andreas Horn et al. Nature Communication


Optimal stimulation sites and networks for deep brain stimulation of the fornix in Alzheimer’s disease

Deep brain stimulation (DBS) of the fornix is ​​an experimental treatment for patients with mild Alzheimer’s disease.

Results from randomized clinical trials have shown that cognitive function improved in some patients but deteriorated in others. This could be explained by variance in electrode placement leading to differential engagement of neural circuits.

To investigate this, we performed a post-hoc analysis on a multicenter cohort of 46 patients with fornix DBS (NCT00658125, NCT01608061). Using normative structural and functional connectivity data, we found that stimulation of the Papez circuit and stria terminalis is strongly associated with cognitive improvement (R= 0.53, p< 0.001).

Locally, the optimal site of stimulation resided at the direct interface between these structures (R= 0.48, p< 0.001).

Finally, modulation of specific memory-related distributed brain networks represented optimal outcomes (R= 0.48, p< 0.001).

The results were robust to multiple cross-validation designs and may define an optimal network target that could fine-tune DBS surgery and programming.

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