Tianjiao Xu, Chunlei Guo, Lei Zhang, Jiudong Cao, Mingyv Li, Jiazheng Li, Kuncheng Li, Jin Yang, Jiliang Fang
Of 9938 unique patients, 1948 underwent AD biomarker testing and 335 received ATT infusions (304 lecanemab, 31 donanemab). The patients who underwent biomarker testing or received ATTs were more likely to be White individuals and to have fewer comorbidities than patients who did not undergo testing or receive ATTs.
BACKGROUND: Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising noninvasive intervention for mild cognitive impairment (MCI), but its clinical efficacy and network-level mechanisms remain unclear.
METHODS: In this prospective, randomized, sham-controlled, parallel-group trial, 60 patients with MCI were assigned 1:1 to 12-week taVNS or sham taVNS. The primary outcome was the between-group difference in change from baseline to week 12 on the Montreal Cognitive Assessment-Basic (MoCA-B). Secondary outcomes included AVLT-H, STT-A/B, AFT, BNT, HAMD-17, and HAMA scores. Twenty-eight healthy controls underwent baseline rs-fMRI as a non-randomized reference cohort. Functional connectivity (FC) identified MCI-related abnormal regions, which together with theory-driven regions served as seeds for Granger causality analysis (GCA) to characterize intervention-related effective connectivity changes. Imaging-behavior associations were examined using Pearson correlations. The final per-protocol analysis included 52 randomized patients with complete clinical and imaging data.
RESULTS: After 12 weeks, the taVNS group showed significant within-group improvements in global cognition and multiple secondary outcomes, whereas the sham group did not. The between-group difference in MoCA-B change was significant (mean difference = 2.91, 95% CI: 0.79 to 5.03, Cohen's d = 0.59), indicating a moderate-to-large effect. Baseline FC abnormalities in MCI mainly involved the insula, medial frontal cortex, precuneus, temporal cortex, thalamus, cingulate cortex, and parieto-occipital regions. Following taVNS, effective connectivity was selectively reconfigured within a distributed network centered on the insula, anterior cingulate cortex, temporal cortex, and precuneus. Changes in directed connectivity correlated with changes in MoCA-B, AFT, and HAMA scores. No serious adverse events occurred.
CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/showproj.html?proj=131823, identifier (ChiCTR2100049940).