Tai Chi-Induced Exosomal LRP1 is Associated With Memory Function and Hippocampus Plasticity in aMCI Patients.

OBJECTIVES: The study was designed to identify the potential peripheral processes of circulating exosome in response to Tai Chi (TC) exercise and the possibility of its loaded cargos in mediating the effects of TC training on cognitive function among older adults with amnestic mild cognitive impairment (aMCI). DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter randomized controlled trial. One hundred community-dwelling old adults with aMCI were randomly assigned (1:1) to experimental (n = 50) and control groups (n = 50). INTERVENTION: The experimental group participated in TC exercise 5 times/week, with each session lasting 60 minutes for 12 weeks. Both experimental and control groups received health education every 4 weeks. MEASUREMENTS: The primary outcome was global cognitive function. Neurocognitive assessments, MRI examination, and large-scale proteomics analysis of peripheric exosome were conducted at baseline and after 12-week training. Outcome assessors and statisticians were blinded to group allocation. RESULTS: A total of 96 participants (96%) completed all outcome measurements. TC training improved global cognitive function (adjusted mean difference [MD] = 1.9, 95%CI 0.93-2.87, p <0.001) and memory (adjusted MD = 6.42, 95%CI 2.09-10.74, p = 0.004), increased right hippocampus volume (adjusted MD = 88.52, 95%CI 13.63-163.4, p = 0.021), and enhanced rest state functional connectivity (rsFC) between hippocampus and cuneus, which mediated the group effect on global cognitive function (bootstrapping CIs: [0.0208, 1.2826], [0.0689, 1.2211]) and verbal delay recall (bootstrapping CI: [0.0002, 0.6277]). Simultaneously, 24 differentially expressed exosomal proteins were detected in tandem mass tag-labelling proteomic analysis. Of which, the candidate protein low-density lipoprotein receptor-related protein 1 (LRP1) was further confirmed by parallel reaction monitoring and ELISA. Moreover, the up-regulated LRP1 was both positively associated with verbal delay recall and rsFC (left hippocampus-right cuneus). CONCLUSION: TC promotes LRP1 release via exosome, which was associated with enhanced memory function and hippocampus plasticity in aMCI patients. Our findings provided an insight into potential therapeutic neurobiological targets focusing on peripheric exosome in respond to TC exercise.

Effects of exercise interventions on executive function in old adults with mild cognitive impairment: A systematic review and meta-analysis of randomized controlled trials.

AIMS: To assess the effect of exercise interventions on subdomains of executive function (EF) in older adults with mild cognitive impairment (MCI). METHODS: Nine electronic databases were comprehensively searched from their inception to February 2021. Randomized controlled trials examining the effect of exercise training on EF in MCI were included. RESULTS: Twenty-four eligible articles involving 2278 participants were identified. The results showed that exercise interventions had positive benefits on working memory, switching and inhibition in MCI. Subgroup analysis based on exercise prescriptions revealed that both aerobatic exercise and mind-body exercise had similar positive effect size on working memory. However, only mind-body exercise had significant effect on switching. Exercise training with moderate frequency (3-4 times/week) had larger effect size than low frequency (1-2 times/week) and only moderate frequency had positive benefits on switching. Both short (4-12 weeks), medium (13-24 weeks) and long (more than 24 weeks) exercise duration significantly ameliorate working memory and switching, however with short duration having slight larger effect sizes than medium and long. CONCLUSION: Exercise significantly improves three subdomains of EF in MCI, especially mind-body exercise. Exercise training sticking to at least 4 weeks with 3-4 times a week tends to have larger effect size.

The impact of physical activity on blood inflammatory cytokines and neuroprotective factors in individuals with mild cognitive impairment: a systematic review and meta-analysis of randomized-controlled trials.

BACKGROUND: Accumulated evidence has proved that both neuroinflammation and neuroprotection existing at the stage of mild cognitive impairment (MCI) may mediate its progression, which can conversely be modulated by physical activity (PA). However, further research is needed to clarify which factors are involved in that process. OBJECTIVES: To identify the impact of PA on inflammatory cytokines and neuroprotective factors in individuals with MCI. METHODS: Four databases [PubMed, Cochrane Library, Cochrane Library (Trials), Embase and Web of Science Core Collection] were searched from their inception to October 2021 for randomized-controlled trials (RCTs) assessing the biochemical effect of PA on biomarkers in participants with MCI. Pooled effect size was calculated by the standardized mean difference (SMD). RESULTS: A total of 13 RCTs involving 514 participants by reporting 8 inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, -6, -8, -10, -15, C-reactive protein (CRP) and interferon-γ (IFN-γ) and 5 neuroprotective factors (brain-derived neurotrophic factor (BDNF), insulin-like growth factor (IGF-1), vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), irisin] were included. The meta-analysis showed that PA had positive effects on decreasing TNF-α (SMD = - 0.32, 95% CI - 0.58 to 0.07, p = 0.01; I2 = 32%) and CRP (SMD = - 0.68, 95% CI - 1.05 to 0.32, p = 0.0002; I2 = 18%), while significantly improving BDNF (SMD = 0.32, 95% CI 0.09-0.56, p = 0.007; I2 = 42%) and IGF-1 (SMD = 0.42, 95% CI 0.03-0.81, p = 0.03; I2 = 0%). CONCLUSION: PA had a certain effect on inhibiting inflammatory cytokines but promoting neuroprotective factors in individuals with MCI which may provide a possible explanation for the potential molecular mechanism of PA on cognitive improvement.