Deep brain stimulation for the treatment of Alzheimer’s disease: A safer and more effective strategy

Abstract Alzheimer’s disease is the most common type of cognitive disorder, and there is an urgent need to develop more effective, targeted and safer therapies for patients with this condition. Deep brain stimulation is an invasive surgical treatment that modulates abnormal neural activity by implanting electrodes into specific brain areas followed by electrical stimulation. As an emerging therapeutic approach, deep brain stimulation shows significant promise as a potential new therapy for Alzheimer’s disease. Here, we review the potential mechanisms and therapeutic effects of deep brain stimulation in the treatment of Alzheimer’s disease based on existing clinical and basic research. In clinical studies, the most commonly targeted sites include the fornix, the nucleus basalis of Meynert, and the ventral capsule/ventral striatum. Basic research has found that the most frequently targeted areas include the fornix, nucleus basalis of Meynert, hippocampus, entorhinal cortex, and rostral intralaminar thalamic nucleus. All of these individual targets exhibit therapeutic potential for patients with Alzheimer’s disease and associated mechanisms of action have been investigated. Deep brain stimulation may exert therapeutic effects on Alzheimer’s disease through various mechanisms, including reducing the deposition of amyloid-β, activation of the cholinergic system, increasing the levels of neurotrophic factors, enhancing synaptic activity and plasticity, promoting neurogenesis, and improving glucose metabolism. Currently, clinical trials investigating deep brain stimulation for Alzheimer’s disease remain insufficient. In the future, it is essential to focus on translating preclinical mechanisms into clinical trials. Furthermore, consecutive follow-up studies are needed to evaluate the long-term safety and efficacy of deep brain stimulation for Alzheimer’s disease, including cognitive function, neuropsychiatric symptoms, quality of life and changes in Alzheimer’s disease biomarkers. Researchers must also prioritize the initiation of multi-center clinical trials of deep brain stimulation with large sample sizes and target earlier therapeutic windows, such as the prodromal and even the preclinical stages of Alzheimer’s disease. Adopting these approaches will permit the efficient exploration of more effective and safer deep brain stimulation therapies for patients with Alzheimer’s disease.