Blood biomarkers of frailty and cognition: A scoping review

Frailty increasingly is recognized as a factor that modifies the relationship between disease biomarkers, including neuropathology, and dementia expression. The mechanisms underlying the relationship between frailty and dementia remain unclear, but blood biomarkers can offer insight into these mechanisms. We completed a scoping review of research examining the associations between blood biomarkers, frailty, and cognition. Three online databases were searched to identify original research examining blood biomarkers in the context of frailty and/or cognitive decline that accounted for the other condition in the analysis through stratification or inclusion in the model. Five of the 76 unique biomarkers identified —A disintegrin and Metalloproteinase 10 (ADAM10), fibrinogen, interleukin (IL)-6, neurofilament light chain (NfL) and vitamin D— were significantly and independently associated with both frailty and cognition. All five biomarkers could contribute to aging mechanisms, including disrupted proteostasis, chronic inflammation, dysregulated metabolism and/or deregulated nutrient sensing. These biomarkers could thus be common pathways of frailty and cognitive decline. Despite the Alzheimer-defining roles of β-amyloid and phosphorylated tau, these biomarkers typically are reported without considering the degree of frailty. Future biomarker research in cognitive decline and frailty should seek a clearer understanding of their relationship. • We reviewed 33 articles exploring blood biomarkers in frailty and cognitive decline • ADAM10, vitamin D, fibrinogen, IL-6, and NfL are altered in both processes • Most biomarkers were involved in inflammation and nutrient sensing • Most studies did not report coefficients/estimates for both frailty and cognition • Most studies were not interested in sex differences in blood biomarkers