Abstract
Declines in both physical and cognitive function are associated with increasing age. Understanding the physiological link between physical frailty and cognitive decline may allow us to develop interventions that prevent and treat both conditions. Although there is significant epidemiological evidence linking physical frailty to cognitive decline, a complete understanding of the underpinning biological basis of the two disorders remains fragmented. This narrative review discusses insights into the potential roles of chronic inflammation, impaired hypothalamic-pituitary axis stress response, imbalanced energy metabolism, mitochondrial dysfunction, oxidative stress, and neuroendocrine dysfunction linking physical frailty with cognitive decline. We highlight the importance of easier identification of strategic approaches delaying the progression and onset of physical frailty and cognitive decline as well as preventing disability in the older population.
Highlights
Declines in both physical and cognitive function are associated with increasing age
Impaired hypothalamic-pituitary axis (HPA) stress responses, imbalanced energy metabolism, mitochondrial dysfunction, oxidative stress, and neuroendocrine dysfunction may be associated with both physical and cognitive decline, and may be involved in mechanisms underlying the link between physical frailty and cognitive decline (Fig. 2)
Inflammaging refers to the low-grade systemic proinflammatory state resulting from the upregulation of the inflammatory response driven by multiple factors in old age [20,21]
Summary
Declines in both physical and cognitive function are associated with increasing age. Sarcopenia, a condition of loss of muscle mass and function, increases the risk of physical frailty and is associated with cognitive impairment [8]. TNF-α and IL-6 influence the onset of frailty and cognitive decline [25], and CRP levels link muscle quality with cognitive function [26].
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