Vagus nerve stimulation in dementia: A scoping review of clinical and pre-clinical studies

Background: Dementia is a prevalent, progressive, neurodegenerative condition with multifactorial causes. Due to the lack of effective pharmaceutical treatments for dementia, there are growing clinical and research interests in using vagus nerve stimulation (VNS) as a potential non- pharmacological therapy for dementia. However, the extent of the research volume and nature into the effects of VNS on dementia is not well understood. This study aimed to examine the extent and nature of research activities in relation to the use of VNS in dementia and disseminate research findings for the potential utility in dementia care. Methods: We performed a scoping review of literature searches in PubMed, HINARI, Google Scholar, and the Cochrane databases from 1980 to November 30th, 2023, including the reference lists of the identified studies. The following search terms were utilized: brain stimulation, dementia, Alzheimer's disease, vagal stimulation, memory loss, Deme*, cognit*, VNS, and Cranial nerve stimulation. The included studies met the following conditions: primary research articles pertaining to both humans and animals for both longitudinal and cross-sectional study designs and published in English from January 1st, 1980, to November 30th, 2023; investigated VNS in either dementia or cognitive impairment; and were not case studies, conference proceedings/abstracts, commentaries, or ordinary review papers. Findings and conclusions: We identified 8062 articles, and after screening for eligibility (sequentially by titles, abstracts and full text reading, and duplicate removal), 10 studies were included in the review. All the studies included in this literature review were conducted over the last three decades in high-income geographical regions (i.e., Europe, the United States, the United Kingdom, and China), with the majority of them (7/10) being performed in humans. The main reported outcomes of VNS in the dementia cases were enhanced cognitive functions, an increased functional connectivity of various brain regions involved in learning and memory, microglial structural modifications from neurodestructive to neuroprotective configurations, a reduction of cerebral spinal fluid tau-proteins, and significant evoked brain tissue potentials that could be utilized to diagnose neurodegenerative disorders. The study outcomes highlight the potential for VNS to be used as a non-pharmacological therapy for cognitive impairment in dementia-related diseases such as Alzheimer's disease.