Biomarkers of Age-Related Frailty and Frailty Related to Disease: 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 [β = 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 [β = -2.42 (-4.76, -0.08)], Omega 3 Index [β = -0.50 (-0.95, -0.06)] and hippocampal volume [β = -0.22 (-0.42,-0.02)]. They also had higher values of GDF15 [β = 246.1 (88.9, 403.4)] and TNFR1 [β = 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.