Biomarkers of Age-Related Frailty and Frailty Related to Diseases: An Exploratory, Cross-Sectional Analysis from the MAPT Study

Background Frailty may in most cases result from two main causes: the aging process (age-related frailty) and diseases (evolving chronic conditions or acute medical illnesses - disease-related frailty). The biological determinants characterizing these two main causes of frailty may be different. Objectives The aim of this study is to compare the biological and neuroimaging profile of people without frailty, those with age-related frailty, and subjects with disease-related frailty in community-dwelling older adults. Material and Methods We performed a secondary, cross-sectional analysis from the Multidomain Alzheimer Preventive Trial (MAPT). We included 1199 subjects without frailty throughout the 5-year follow-up, 82 subjects with incident age-related frailty, and 53 with incident disease-related frailty. Available blood biomarkers involved nutritional (eg, vitamin D, omega-3 fatty acids), inflammatory-related (IL-6, TNFR1, GDF15), neurodegenerative (eg, beta-amyloid, neurofilament light chain) and neuroimaging markers (MRI, Amyloid-PET). Results Although not statistically significant, the results of the unadjusted model showed increasing gradients for inflammatory markers (GDF15, TNFR1) and decreasing gradients for nutritional and neuroimaging markers (omega 3 index, hippocampal volume) from age-related frailty participants to individuals with disease-related frailty. Considering the linear models we observed higher GDF15 values in disease-related frailty group compared to age-related frailty individuals [beta = 242.8 (49.5, 436.2)]. We did not find any significant difference between subjects without frailty and those with age-related frailty. Subjects with disease-related frailty compared to subjects without frailty had lower values of DHA [beta = -2.42 (-4.76, -0.08)], Omega 3 Index [beta = -0.50 (-0.95, -0.06)] and hippocampal volume [beta = -0.22 (-0.42,-0.02)]. They also had higher values of GDF15 [beta = 246.1 (88.9, 403.4)] and TNFR1 [beta = 157.5 (7.8, 307.2)]. Conclusion Age-related frailty and disease-related frailty may represent different degrees of frailty severity on a biological level. Further research is needed to identify biomarkers potentially able to distinguish these classifications of frailty.