• Jie Ma, Jia-Jia Wu, Xiang-Xin Xing, Xin Xue, Yun-Ting Xiang, Xiao-Min Zhen, Jian-Hua Li, Juan-Juan Lu, Jun-Peng Zhang, Mou-Xiong Zheng, Xu-Yun Hua, and Jian-Guang Xu.
• Center of Rehabilitation Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
• J. Neurol. Neurosurg. Psychiatr. 2024 Sep 17; 95 (10): 902911902-911.

BackgroundThis study aimed to investigate the efficacy of circuits-based paired associative stimulation (PAS) in adults with amnestic mild cognitive impairment (aMCI).MethodsWe conducted a parallel-group, randomised, controlled clinical trial. Initially, a cohort of healthy subjects was recruited to establish the cortical-hippocampal circuits by tracking white matter fibre connections using diffusion tensor imaging. Subsequently, patients diagnosed with aMCI, matched for age and education, were randomly allocated in a 1:1 ratio to undergo a 2-week intervention, either circuit-based PAS or sham PAS. Additionally, we explored the relationship between changes in cognitive performance and the functional connectivity (FC) of cortical-hippocampal circuits.ResultsFCs between hippocampus and precuneus and between hippocampus and superior frontal gyrus (orbital part) were most closely associated with the Auditory Verbal Learning Test (AVLT)_N5 score in 42 aMCI patients, thus designated as target circuits. The AVLT_N5 score improved from 2.43 (1.43) to 5.29 (1.98) in the circuit-based PAS group, compared with 2.52 (1.44) to 3.86 (2.39) in the sham PAS group (p=0.003; Cohen's d=0.97). A significant decrease was noted in FC between the left hippocampus and left precuneus in the circuit-based PAS group from baseline to postintervention (p=0.013). Using a generalised linear model, significant group×FC interaction effects for the improvements in AVLT_N5 scores were found within the circuit-based PAS group (B=3.4, p=0.017).ConclusionsCircuit-based PAS effectively enhances long-term delayed recall in adults diagnosed with aMCI, which includes individuals aged 50-80 years. This enhancement is potentially linked to the decreased functional connectivity between the left hippocampus and left precuneus.Trial Registration NumberChiCTR2100053315; Chinese Clinical Trial Registry.© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

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