Understanding the Physiological Links Between Physical Frailty and Cognitive Decline

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.

Keywords: biology; cognitive decline; cognitive frailty; physical frailty.

Figure 1.

The model of cognitive frailty. Physical frailty and cognitive impairment have the same etiology, and might share the same mechanisms, which lead to adverse health outcomes. The decline in physical reserve and cognitive function contribute to frailty and cognitive impairment separately. Cognitive frailty is the combination of frailty and cognitive impairment in absence of dementia, which is further divided into reversible cognitive frailty (prefrailty and subjective cognitive decline) and potentially reversible cognitive frailty (physical frailty and mild cognitive impairment).Abbreviations: CF, cognitive frailty; SCD, subjective cognitive decline; MCI, mild cognitive impairment; AD, Alzheimer's disease.

Figure 2.

Overview of the underlying mechanisms linking physical frailty to cognitive decline. Chronic inflammation, impaired HPA stress response, imbalanced energy metabolism, endocrine dysregulation, mitochondrial dysfunction, oxidative stress, genomic markers and metabolomic markers are major underlying mechanisms between physical frailty (muscle) and cognitive decline (brain).