Only recently, a large-scale clinical study demonstrated for the first time that a monoclonal antibody (lecanemab) can delay the progression of the disease in Alzheimer’s patients by 27 percent. Berlin neurology scientists are active in a different way. After a random observation, they identified an area of the brain in Alzheimer’s patients that apparently responds to electrical stimulation.
The procedure involves deep brain stimulation (DBS). It is a form of therapy that has long been approved for the treatment of neurological movement disorders such as Parkinson’s disease and neuropsychiatric disorders (eg obsessive-compulsive disorders). For this purpose, fine electrodes are implanted in the brain of those affected, which constantly emit weak, short electrical impulses to the respective brain regions. The electrodes remain in the brain and are connected to a pacemaker in the chest by wires that run under the skin. It can be used to adjust the current and frequency. Good treatment successes have been proven especially in Parkinson’s disease.
improve quality of life
Andreas Horn from the Department of Neurology with Experimental Neurology at the Berlin University Hospital Charite and an international team of scientists want to make Alzheimer’s dementia an area of application for this “electrotherapy”. The expert: “DBS works very well in Parkinson’s disease, the quality of life of the patients improves significantly.” Like Parkinson’s disease, Alzheimer’s disease is one of the neurodegenerative diseases, so a possible therapeutic application of DBS would be obvious. For a safe and effective therapy, however, a suitable target region in the brain must be identified, the stimulation of which will trigger a positive effect.
The starting point of a current study, which was published in “Nature Communications” on Wednesday (doi: 10.1038/s41467-022-34510-3), was an observation by cooperation partners at the University of Toronto in Canada, the Charite announced. “In a patient who was being treated for obesity, deep brain stimulation triggered flashbacks – i.e. sudden memories from childhood and adolescence,” explained Ana Sofia Rios from the Berlin University Hospital. “It was therefore reasonable to assume that the stimulated brain region, which was located in the area of the so-called fornix, might possibly also be suitable for treating Alzheimer’s disease.”
The so-called fornix is a structure in both hemispheres of the brain in the limbic system of the brain. This nerve cell fiber tissue plays a role in converting the contents of short-term to long-term memory and thus in learning processes.
In order to follow up the observation in the obese patient, researchers at seven international centers implanted electrodes in the area of the fornix in patients suffering from mild Alzheimer’s dementia as part of another multi-centre study. “Unfortunately, most patients did not see any improvement in their symptoms. However, a few study participants benefited significantly from the treatment,” said Ana Sofia Rios. “We wanted to find out how this difference came regarding and compared the exact position of the electrodes between the study participants.”
Horn and his team have specialized in analyzing high-resolution images of the brain that are recorded using magnetic resonance imaging and, in combination with computer models, in precisely detecting the optimal stimulation points for DBS in the brain. “A particular challenge here is that every brain is different. And that plays a major role in the implantation of the electrodes,” the expert was quoted as saying in a broadcast from the university clinic. “If you’re just a few millimeters off, the expected effect may not be there.”
Precisely determine the target structure for electrodes
This was also the case for the majority of the 46 study participants with Alzheimer’s disease. However, in those patients in whom DBS showed a positive effect, the target structure for the electrodes might finally be pinpointed. “It lies at a branch point between two nerve fiber bundles – the fornix and the stria terminalis – that connect deep brain regions. Both structures are associated with memory function,” explained the neuroscientist.
Further clinical studies are required before DBS can be approved and used for the treatment of Alzheimer’s disease. But with the data for the precise implantation of the electrode, there is a basis for further clinical studies. “If our data helps to place the electrodes more precisely in neurosurgical studies testing DBS in Alzheimer’s, that would be great,” said Horn. “Because we urgently need an effective and symptom-relieving therapy for Alzheimer’s in order to be able to help the patients – DBS is a promising approach for this.”
Around 55 million people worldwide suffered from dementia in 2019, most of them from Alzheimer’s disease. The numbers are constantly increasing due to age development. The costs due to such diseases have been calculated at more than 800 billion euros per year. The drugs used to date for Alzheimer’s disease, for example the so-called cholinesterase inhibitors, only have a relatively weak effect on the symptoms. Causal therapies aim to eliminate harmful deposits of the proteins beta-amyloid or tau. Monoclonal antibodies, such as lecanemab, are to be used once morest beta-amyloid. However, many such projects have failed so far. In the recent past, this has also led to considerable doubts as to whether beta-amyloid or tau proteins are really causally related to Alzheimer’s dementia.