Clinical Exploratory Research of Medial Prefrontal Cortex Combined With Dorsolateral Prefrontal Cortex Electrical Stimulation in the Treatment of Alzheimer's Disease

The main principle of DBS is to regulate the activity of neural components by implanting electrodes into key brain regions using a built-in pulse generator. The basic principle of using DBS in AD is that AD is not only a neurodegenerative disease, but also a neural circuit disease, because it affects several integrated cortical and subcortical pathways, especially those involving memory and cognition. DBS implants stimulation electrodes into deep neural nuclei in the brain for electrical stimulation, altering the excitability of the corresponding nuclei or neural circuits, which may lead to therapeutic effects. However, the stimulation targets of the electrodes are still unclear.

There are currently 3 clinical studies on AD-DBS reported in the literature, using stimulation targets such as the Basal Nucleus of Meynert (NBM) and the fornix. One of the studies was reported this year by a team from Kuhn et al. in Germany. They used NBM as a stimulation target and treated 6 patients with DBS. The stimulation lasted for 12 months and was evaluated using the Alzheimer's Disease Assessment Scale - Cognitive Scale (ADAS Co g) and the Simplified Mental State Examination Scale (MMSE). Among them, one patient showed improvement in their ADAS Log score, two patients stabilized, and three patients continued to deteriorate in cognitive function. The other was a phase I clinical trial conducted by the Lozano team in Canada in 2010. The team used the fornix as a stimulation target to perform DBS treatment on 6 mild AD patients, with the same stimulation for 12 months. The results showed that only 1 out of 6 patients had significant improvement in cognitive function (reduced ADAS Cog score), while the remaining 5 patients still showed varying degrees of deterioration. In addition, Fontaine et al. reported in 2013 on a patient with transfornix electrical stimulation, where 12 months of continuous electrical stimulation stabilized the patient's MMSE and ADAS-Log scores. However, the above three studies all found that DBS can improve the glucose metabolism level of brain tissues in temporal and parietal lobes. The above studies indicate that although NBM and fornix electrical stimulation have some improvement in cognitive function in some AD patients, the overall improvement rate is low, with most patients in an unresponsive state. Therefore, given the core position of stimulation targets in deep brain electrical stimulation surgery, it is urgent to explore new stimulation targets in order to improve the efficacy of DBS. The combination of medial prefrontal cortex (mPFC) and dorsolateral prefrontal cortex (dlPFC) can serve as an ideal stimulation target At present, the treatment of AD is still a global challenge, but the non-invasive neural regulation techniques (rTMS and tDCS) based on the medial prefrontal cortex (mPFC) and dorsolateral prefrontal cortex (dlPFC) have preliminarily confirmed that mPFC and dlPFC regions may be potential therapeutic targets for AD, which can significantly improve the cognitive status of therapists. At present, the targets used for treating AD with DBS are the fornix and NBM, but the effectiveness of treating AD has not been confirmed. Based on a thorough analysis of current international research and in conjunction with previous research conducted by our center, the investigators propose to combine the left mPFC and dlPFC regions as stimulation targets and innovatively use sheet electrodes for cortical brain stimulation (CBS), which is well established. As a stimulation method of DBS, CBS stimulates the cortex relative to the deep stimulation target. For example, common pain electrical stimulation uses CBS, so the cortical electrical stimulation in this study adopts the naming method of CBS. On this basis, the investigators strictly set inclusion and exclusion criteria to ensure the quality of enrolled patients, and conducted thorough experimental design and validated the efficacy of CBS in treating AD from multiple perspectives using specific memory and cognitive function assessment scales, fusion function, structure, metabolic brain networks, and other methods.