Sarcopenia in cognitive disorders: Toward a shared pathophysiological framework

Sarcopenia and cognitive disorders frequently co-occur and may share convergent biology spanning systemic inflammation, vascular dysfunction, oxidative stress, and hormonal-metabolic dysregulation. Literature search was conducted using PubMed, Cochrane, Embase, and CENTRAL from January 2000 to March 2026. Search terms included "Sarcopenia", "Mild Cognitive Impairment", and "Dementia". Eighty-two studies met inclusion criteria (54 clinical; 28 interventions), discussing epidemiological trends, mechanistic pathways, biomarkers, and therapeutic targets. Clinical evidence clustered across inflammation, vascular change and energetics, hormonal-metabolic dysregulation, and biomarkers. Elevated inflammatory mediators tracked slower gait, weaker grip, and poorer cognition, mapping to mobility decline and Montreal Cognitive Assessment (MoCA) deficits. Cross-domain readouts linked muscle and brain: muscular fat infiltration related to worse cognitive-motor performance; temporalis muscle thickness correlated with MoCA and tau signal; impaired post-exercise phosphocreatine recovery associated with higher neurodegeneration risk and slower processing/gait. Blood biomarkers consistently stratified motor-cognitive status/decline. Among intervention reports, aerobic/resistance training improved strength, mobility, and often processing outcomes; protein (± vitamin D) and n-3 polyunsaturated fatty acid showed supportive but heterogeneous effects; vitamin D alone showed mixed muscle results but associated with lower dementia incidence; single-pathway metabolic/anti-cytokine strategies were mixed. Few studies powered dual musculoskeletal-cognitive endpoints, limiting quantitative synthesis. There is compelling evidence for bidirectional crosstalk between sarcopenia and cognitive impairment. However, evidence substantiating shared interventions remains limited and could benefit from more multi-center dual-outcome randomized controlled trials. Establishing consensus risk stratification criteria based on common biomarkers may support integrated management of these conditions, improving patient outcomes.