Integrative physiology of skeletal muscle for maintaining cognitive health

Cognitive decline and physical impairment are often linked with ageing, contributing to declines in health span and loss of independence in older adults. Pathological cognitive decline with age is largely considered to be a brain-centric challenge. However, recent findings have begun to challenge this paradigm as the health of peripheral systems, namely skeletal muscle, predict cognitive decline associated with Alzheimer's disease (AD). Loss of muscle strength (dynapenia), loss of muscle mass (sarcopenia) and associated impairment in peripheral motor nerves and neuromuscular junctions have all been shown to either precede or coincide with AD pathology in the brain. The importance for skeletal muscle is also demonstrated in its role as an endocrine organ, secreting factors like brain-derived neurotrophic factor that promote neurogenesis in the brain. In this review we summarize the importance of skeletal muscle for cognition and discuss how the health of skeletal muscle and peripheral motor nerves may be novel sentinels for AD risk.