Qigong exercise enhances cognitive functions in the elderly via an interleukin-6-hippocampus pathway: a randomized active-controlled trial Author: Di Qi1, Nichol M L Wong1, Robin Shao1, Idy S C Man1, Clive H Y Wong1, Lai Ping Yuen2, Chetwyn C H Chan3, Tatia M C Lee4 Affiliation: <sup>1</sup> State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong; Laboratory of Neuropsychology and Human Neuroscience, The University of Hong Kong, Hong Kong. <sup>2</sup> State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong. Electronic address: neuropsy@hku.hk. <sup>3</sup> Applied Cognitive Neuroscience Laboratory, Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong. Electronic address: Chetwyn.Chan@polyu.edu.hk. <sup>4</sup> State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong; Laboratory of Neuropsychology and Human Neuroscience, The University of Hong Kong, Hong Kong; Institute of Clinical Neuropsychology, The University of Hong Kong, Hong Kong. Electronic address: tmclee@hku.hk. Conference/Journal: Brain Behav Immun Date published: 2021 Apr 16 Other: Special Notes: doi: 10.1016/j.bbi.2021.04.011. , Word Count: 310 Background: Evidence has suggested that exercise protects against cognitive decline in aging, but the recent lockdown measures associated with the COVID-19 pandemic have limited the opportunity for outdoor exercise. Herein we tested the effects of an indoor exercise, Qigong, on neurocognitive functioning as well as its potential neuro-immune pathway. Methods: We conducted a 12-week randomized active-controlled trial with two study arms in cognitively healthy older people. We applied Wu Xing Ping Heng Gong (Qigong), which was designed by an experienced Daoist Qigong master, to the experimental group, whereas we applied the physical stretching exercise to the control group. The Qigong exercise consisted of a range of movements involving the stretching of arms and legs, the turning of the torso, and relaxing, which would follow the fundamental principles of Daoism and traditional Chinese medicine (e.g., Qi). We measured aging-sensitive neurocognitive abilities, serum interleukin-6 (IL-6) levels, and brain structural volumes in the experimental (Qigong, n= 22) and control groups (stretching, n = 26) before and after the 12-week training. Results: We observed that Qigong caused significant improvement in processing speed (t (46) = 2.03, p = 0.048) and sustained attention (t (46) = -2.34, p = 0.023), increased hippocampal volume (t (41) = 3.94, p < 0.001), and reduced peripheral IL-6 levels (t (46) = -3.17, p = 0.003). Moreover, following Qigong training, greater reduction of peripheral IL-6 levels was associated with a greater increase of processing speed performance (bootstrapping CI: [0.16, 3.30]) and a more significant training-induced effect of hippocampal volume on the improvement in sustained attention (bootstrapping CI: [-0.35, -0.004]). Conclusion: Overall, these findings offer significant insight into the mechanistic role of peripheral IL-6-and its intricate interplay with neural processes-in the beneficial neurocognitive effects of Qigong. The findings have profound implications for early identification and intervention of older individuals vulnerable to cognitive decline, focusing on the neuro-immune pathway. The trial was registered at clinicaltrials.gov (identifier: NCT04641429). Keywords: Aging; Cognition; Gray matter volume; Hippocampus; Interleukin-6; Qigong. PMID: 33872709 DOI: 10.1016/j.bbi.2021.04.011