A systematic review of exercise modalities that reduce pro-inflammatory cytokines in humans and animals' models with mild cognitive impairment or dementia

Exp Gerontol. 2023 Mar 14;175:112141. doi: 10.1016/j.exger.2023.112141. Online ahead of print.


Purpose: To investigate which type, frequency, duration, intensity, and volume of chronic exercise might more strongly reduce pro-inflammatory cytokines and enhance anti-inflammatory cytokines in human and animal models with Mild Cognitive Impairment (MCI) or dementia.

Design: A systematic review.

Data source: English-language search of 13 electronic databases: Web of Science, PubMed/Medline, Sport Discus, Scopus, Cochrane, Psych Net, Springer, ScienceDirect, Pascal & Francis, Sage journals, Pedro, Google Scholar, and Sage.

Inclusion criteria: (i) human and animal studies that included exercise, physical activity, or fitness training as an experimental intervention, (ii) studies that addressed MCI, dementia, or AD, (iii) studies that focused on measuring cytokines and/or other inflammatory and/or neuroinflammatory immune markers, (iii) studies that examined inflammatory indicators in blood, CSF (Cerebrospinal Fluid), and brain tissue.

Results: Of the 1290 human and animal studies found, 38 were included for qualitative analysis, 11 human articles, 27 animal articles, and two articles addressing both human and animal protocols. In the animal model, physical exercise decreased pro-inflammatory markers in 70.8 % of the articles and anti-inflammatory cytokines: IL -4, IL -10, IL-4β, IL -10β, and TGF-β in 26 % of articles. Treadmill running, resistance exercise, and swimming exercise reduce pro-inflammatory cytokines and increase anti-inflammatory cytokines. In the human model, 53.9 % of items reduced pro-inflammatory proteins and 23 % increased anti-inflammatory proteins. Cycling exercise, multimodal, and resistance training effectively decreased pro-inflammatory cytokines.

Conclusion: In rodent animal models with AD phenotype, treadmill, swimming, and resistance training remain good interventions that can delay various mechanisms of dementia progression. In the human model, aerobic, multimodal, and resistance training are beneficial in both MCI and AD. Multimodal training of moderate to high intensity multimodal exercise is effective for MCI. Voluntary cycling training, moderate- or high-intensity aerobic exercise is effective in mild AD patients.

Keywords: Alzheimer's disease; Chronic exercise; Cognitive decline; Cytokines; Neuro inflammation.

Publication types

  • Review