Deep brain stimulation of fornix for memory improvement in Alzheimer’s disease: A critical review

Memory reflects the brain function in encoding, storage and retrieval of the data or information, which is a fundamental ability for any live organism. The development of approaches to improve memory attracts much attention due to the underlying mechanistic insight and therapeutic potential to treat neurodegenerative diseases with memory loss, such as Alzheimer’s disease (AD). Deep brain stimulation (DBS), a reversible, adjustable, and non-ablative therapy, has been shown to be safe and effective in many clinical trials for neurodegenerative and neuropsychiatric disorders. Among all potential regions with access to invasive electrodes, fornix is considered as it is the major afferent and efferent connection of the hippocampus known to be closely associated with learning and memory. Indeed, clinical trials have demonstrated that fornix DBS globally improved cognitive function in a subset of patients with AD, indicating fornix can serve as a potential target for neurosurgical intervention in treating memory impairment in AD. The present review aims to provide a better understanding of recent progresses in the application of fornix DBS for ameliorating memory impairments in AD patients. •Fornix, a core component of limbic system, plays an essential role in memory.•Fornix DBS could be a promising therapeutic intervention for AD.•At least five putative neurobiological mechanisms mediate the therapeutic actions of fornix DBS treatment•Randomized, double-blind, and multi-clinical trials are needed to verify the safety and efficacy of fornix DBS for AD.