Intersection of Sarcopenia and cognitive decline: An umbrella review using HOMA-IR and NIRS

Abstract

Sarcopenia and cognitive decline frequently co-occur in ageing populations and share overlapping biological pathways, including physical inactivity, insulin resistance, mitochondrial dysfunction, inflammation, and altered muscle-brain signalling. Skeletal muscles, as a key insulin-sensitive and endocrine organ, may play a central role in linking metabolic dysfunction to neurocognitive impairment. However, the mechanistic integration of systemic metabolic markers and muscle-specific physiological measures remains insufficiently synthesized. Objective: To synthesize existing evidence on the interrelationships between sarcopenia, insulin resistance and cognitive decline with a specific focus on the roles of the homeostatic model assessment of insulin resistance (HOMA-IR) and nearinfrared spectroscopy (NIRS) as complementary metabolic and physiological assessment tools. Methods: A comprehensive umbrella review was conducted, including narrative reviews, systematic reviews, scoping review, methodological reviews and observational studies published between January 2000 and January 2026. Studies examining associations between physical inactivity or sarcopenia, insulin resistance, muscle or cerebral oxygenation and cognitive outcomes were included. Findings were synthesised qualitatively due to heterogeneity in study design and outcome measures. Results: Population-based studies consistently demonstrated strong associations between sarcopenia and elevated HOMA-IR, independent of obesity. Mechanistic and methodological reviews highlighted impaired muscle oxidative capacity and mitochondrial dysfunction as early features of inactivity and metabolic decline, reliably assessed using NIRS. Preclinical and integrative human evidence supported a muscle-brain axis mediated by insulin resistance, myokine dysregulation and neurotropic signalling, contributing to cognitive impairment. Conclusion: Sarcopenia represents a metabolically active contributor to cognitive decline rather than a passive consequence of ageing. Integrating HOMA-IR and NIRS provides a multidimensional framework for identifying high-risk individuals, monitoring intervention responses and advancing understanding of the muscle-brain axis across the lifespan.