Physical Exercise and Neuroinflammation in Alzheimer’s Disease and Mild Cognitive Impairment: Molecular Mechanisms and Clinical Relevance

Abstract

Background

Alzheimer’s disease (AD) and mild cognitive impairment (MCI) are associated with neuroinflammatory, vascular, and metabolic alterations beyond amyloid-beta and tau pathology. Physical exercise has attracted growing interest as a non-pharmacological intervention, although evidence linking exercise-induced changes in inflammatory pathways to clinical outcomes remains limited.

Aim of the Study

This narrative review critically examines the evidence on whether physical exercise influences neuroinflammatory processes in AD and MCI, with particular attention to biological mechanisms, biomarker interpretation, clinical outcomes, safety, and current research limitations.

Materials and Methods

A structured literature search was conducted using PubMed/MEDLINE, PubMed Central, selected publisher databases, and relevant clinical guidelines. Priority was given to randomized controlled trials, systematic reviews, meta-analyses, consensus statements, and key mechanistic studies. As this was a narrative review rather than a registered systematic review, formal PRISMA reporting, quantitative meta-analysis, and GRADE assessment were not performed.

Conclusion

Physical exercise may be considered a supportive intervention for individuals with MCI and early AD, with potential benefits for physical function, overall health, and possibly cognition. However, current evidence does not support its classification as a disease-modifying anti-neuroinflammatory therapy. Future studies should focus on well-defined patient populations, appropriate active comparators, supervised multimodal exercise programmes, standardized safety reporting, and combined clinical and biomarker outcomes.