Abstract
Frailty is a multifactorial geriatric syndrome characterized by increased vulnerability to stressors and associated with a higher risk of adverse health outcomes. Chronic low-grade inflammation has been proposed as a key pathophysiological mechanism underlying physical frailty, although its role in cognitive frailty remains undefined. In this cross-sectional study, we assessed the relationship between frailty status, both physical and cognitive, and plasma concentrations of six inflammatory biomarkers-C-reactive protein (CRP), interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-α), soluble TNF-α receptor type II (sTNF-RII), high-temperature requirement serine protease A1 (HTRA1), and growth differentiation factor 15 (GDF15)-in a cohort of Spanish older adults (N = 150, ≥ 65 years old), classified according to Fried's frailty phenotype and frailty index. The results showed notable differences between frailty phenotype and frailty index, and highlighted CRP, TNF-α, sTNF-RII, and GDF15 as key biomarkers significantly associated with physical frailty status, with CRP and TNF-α also discriminating pre-frail individuals. sTNF-RII stood out for its high predictive capacity, while GDF15 added value as an indicator of sustained cellular stress. Regarding cognitive frailty, CRP, TNF-α, and GDF15 displayed significant associations with this condition. sTNF-RII and HTRA1, scarcely studied in this context, showed promising and significant associations (specific for cognitive frailty in the case of HTRA1) that justify their inclusion in future research aimed at better understanding the inflammatory mechanisms involved in cognitive frailty.