
Preliminary exploration of the impact of immediate transcutaneous auricular vagus nerve stimulation on brain function imaging in patients with mild cognitive impairment
Chunlei GUO, Yue MA, Shanshan GAO, Yi LUO, Qingyan CHEN, Jiliang FANG
Chinese Journal of Alzheimer's Disease and Related Disorders ›› 2024, Vol. 7 ›› Issue (2) : 94-102.
Abbreviation (ISO4): Chinese Journal of Alzheimer's Disease and Related Disorders
Editor in chief: Jun WANG
Preliminary exploration of the impact of immediate transcutaneous auricular vagus nerve stimulation on brain function imaging in patients with mild cognitive impairment
Objective: This study investigated the impact of immediate (30 minutes) transcutaneous auricular vagus nerve stimulation (taVNS) on brain function in patients with mild cognitive impairment (MCI) using resting-state functional magnetic resonance imaging (rs-fMRI). Methods: The study included 22 MCI patients randomly divided into a taVNS group and a sham taVNS group, with 11 patients in each, as well as 11 healthy controls (HCs). All three groups of subjects underwent 30 minutes of auricular electrical stimulation, with the taVNS group and HCs group receiving stimulation on the concha, located in the main distribution area of the vagus nerve, while the sham taVNS group received stimulation on the non-vagus nerve distributed helicis. Each subject underwent an rs-fMRI scan before and after the stimulation. For preprocessing of the rs-fMRI scan results, DPABI 8.0 was used, followed by calculation of functional connectivity (FC). Comparison of FC images before and after stimulation in three groups of subjects, with the results being extracted and post-hoc analysis performed using Graphpad Prism 9.0.0 to observe the effects of taVNS on brain function. Results: Compared to pre-stimulation, post-stimulation FC values in the taVNS group showed a significant decrease between the right hippocampus and the right cerebellum_6, and a significant increase between the left caudate nucleus and the right superior frontal gyrus (P<0.005), as well as between the right pallidum and the left caudate (P<0.05). In the HCs group, there was a significant decrease in the FC values between the left caudate and the cerebellum_8 after stimulation (P<0.05). Conclusion: Immediate taVNS can modulate brain functional networks related to memory and cognition, as well as the basal ganglia and cerebellum, which may be the effector targets of taVNS treatment for MCI.
Mild cognitive impairment / Transcutaneous auricular vagus nerve stimulation / Resting-state fMRI / Functional connectivity
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It has been reported that up to 42% of the population aged over 60 are affected by mild cognitive impairment (MCI) worldwide. This study aims to investigate the prevalence and progression of MCI through a meta-analysis.We searched Embase and PubMed for relevant literature. Stable disease rate (SR), reversion rate (RR), dementia rate (DR), and Alzheimer's disease rate (AR) were used to evaluate the progression of MCI. The prevalence and progression rates were both obtained by reported percentile and indirect data analysis. Additionally, we carried out sensitivity analysis of each index by excluding some studies due to influence analysis with the most publication bias.Effect size (ES) was used to present adjusted overall prevalence (16%) and progression rates including SR (45%), RR (15%), DR (34%), and AR (28%) of MCI. Compared with clinic-based outcomes, MCI prevalence, SR, and RR are significantly higher in community, while DR and AR are lower. Despite significant heterogeneity found among the studies, no publication bias was observed.Age and gender were observed to be associated with MCI, in which age was considered as an impact factor for DR. The strong heterogeneity may result from variations in study design and baselines. Standardized MCI criteria were suggested to systematically evaluate MCI in the future.
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There are 9.9 million new cases of dementia in the world every year. Short-term conversion rate from mild cognitive impairment (MCI) to dementia is between 20% and 40%, but long-term in 5-10 years ranges from 60% to 100%. It is particularly important to prevent or prolong the development of MCI into dementia. Both auriculotherapy and vagus nerve stimulation are effective on improving cognitive functions. However, there is no double blinded randomized clinical trial to support the effectiveness of transcutaneous electrical stimulation of auricular acupoints in patients with MCI.This randomized controlled trial involved patients with MCI, aged from 55 to 75 years old. Patients were randomly allocated to transcutaneous auricular vagus nerve stimulation (taVNS) group or sham taVNS group. In the taVNS group, two auricular acupoints were stimulated, including heart (concha, CO) and kidney (CO), which are in the distribution of vagus nerve. While in the sham taVNS group, two other auricular acupoints were stimulated, including elbow (scaphoid fossa, SF) and shoulder (SF), which are out of the distribution of vagus nerve. The primary outcome was the Montreal cognitive assessment-basic, MOCA-B. The secondary outcomes included auditory verbal learning test-HuaShan version (AVLT-H), shape trails test A&B (STT-A&B), animal fluence test (AFT), Boston naming test (BNT), Pittsburgh sleep quality index (PSQI), rapid eye movement sleep behavior disorder screening questionnaire (RBDSQ), Epworth sleepiness scale (ESS) and functional activities questionnaire (FAQ). These outcome measures were taken at baseline, 24 weeks later.After 24 weeks of intervention, the data of 52 patients were intended for analysis. After intervention, there was significant difference in the overall scores of MoCA-B between taVNS group and sham taVNS group (p = 0.033 < 0.05). In taVNS group, compared with before intervention, the overall scores of MOCA-B increased significantly after intervention (p < 0.001). As for N5 and N7, the two sub-indicators of AVLT-H, in taVNS group, compared with before intervention, both N5 and N7 increased significantly after intervention (both ps < 0.001). As for STTB, in taVNS group, compared with before intervention, STTB was significantly reduced after intervention (p = 0.016). For BNT, in taVNS group, compared with before intervention, BNT increased significantly after intervention (p < 0.001). In taVNS group, compared with before intervention, PSQI, RBDSQ, ESS and FAQ decreased significantly after intervention (p = 0.002, 0.025, <0.001, 0.006 respectively). 1 patient with a history of tympanic membrane perforation in taVNS group was reported with mild adverse reactions which disappeared a week after termination of taVNS. The intervention of taVNS is effective on increasing the overall scores of MoCA-B, N5 and N7.The clinical trial demonstrated that taVNS can improve cognitive performance in patients with MCI. This inexpensive, effective and innovative method can be recommended as a therapy for more patients with MCI in the prevention or prolonging of its development into dementia, but it is still required to be further investigated.http://www.chictr.org.cn. (ID: ChiCTR2000038868).Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
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Transcutaneous vagus nerve stimulation, which involves the application of electrical currents to the cervical (tcVNS) or auricular (taVNS) branches of the vagus nerve, may be a potential treatment for improving cognitive dysfunction. taVNS may improve cognitive performance in healthy adults, and fewer studies have been performed on the effects of tcVNS on cognition in healthy subjects. We conducted a randomized, single-blind, crossover-controlled trial to investigate the effects of tcVNS stimulation on cognitive function and neural activity in the brains of healthy adults. This study provides support for further tcVNS studies for the treatment of cognitive impairment. Twenty-one participants were randomly divided into two groups, A and B. Group A received tcVNS first and then sham-tcVNS, while group B received the intervention in the reverse order, receiving sham stimulation first and then true stimulation. All subjects were required to perform cognitive function tests before and after receiving intervention, and functional magnetic resonance imaging (fMRI) was performed concurrently during the intervention. We hypothesized that tcVNS would have an effect on the cognitive performance of the subjects and alter the neural activity of the brain. The present study showed that tcVNS had beneficial effects on cognitive performance, mainly improving memory and language skills and attention. tcVNS intervention produced significant spontaneous neural activity in the calcarine gyrus, fusiform gyrus, lingual gyrus, and parahippocampal gyrus of the brain. Future tcVNS/fMRI trials will need to explore the effects of changes in stimulus parameters on the neural activity response of the brain.
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