Osteoarthritis and dementia: contrasting disorders driven by mutual pathways of autophagy, mTOR, GLP-1, AMPK, Wnt, and WISP1.

INTRODUCTION

Increased global lifespan is paralleled by a rise in non-communicable diseases with osteoarthritis and dementia, including Alzheimer's disease, impacting all nations with severe disability, death, and financial burden.

AREAS COVERED: Given that osteoarthritis and dementia are worsened with advancing age, progressive in nature, and presently remain only with symptomatic treatments, development of advanced comprehensive therapies is critical for these disorders. New innovative work offers insight into the underlying clinical bond between degenerative joint disease and cognitive loss. Data sources using systematic literature search employed PubMed, Scopus, Web of Science, and ScienceDirect from January 2021 through February 2026.

EXPERT OPINION: Although affecting diverse organ systems, degenerative joint disease and dementia are intimately connected by shared cellular pathways responsible for disease onset and progression. Pioneering avenues of investigation of oxidative stress, autophagy, the mechanistic target of rapamycin (mTOR), cellular metabolism mechanisms with glucagon-like peptide-1 (GLP-1) receptors and AMP activated protein kinase (AMPK), Wnt signaling, and Wnt1 inducible signaling pathway protein 1 (WISP1) offer exciting treatment opportunities for osteoarthritis and Alzheimer's disease. Ultimately, these complex pathways will necessitate focus upon their intricate dependence that may benefit from several targeted approaches including artificial intelligence applications for fruitful clinical translation.