Neurodegenerative biomarkers, frailty and vulnerability in older adults: cohort perspective
S Meijide de la Fuente, L Altuna Tellechea, M A Lazaro Naranjo, R Coya Guerrero, V Gómez Sánchez, H Martín Rodríguez, M D García Vázquez, M Barasoain Hernández, A Velez del Burgo del Hoyo, R Perez GarayAbstract
Background
Blood-based biomarkers such as phosphorylated tau, amyloid-β, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are promising tools for assessing neurodegenerative processes in older adults, although their interpretation may be influenced by frailty and clinical vulnerability.
Objectives
To investigate the distribution of plasma neurodegenerative biomarkers across clinical cohorts and frailty-related vulnerability profiles in older adults.
Methods
A cohort-based analysis was conducted in 619 participants from the BioSilver study, including ambulatory individuals, acutely hospitalised patients and nursing home residents. Biomarkers analysed were pT217, Aβ42, Aβ40, pT181, GFAP and NfL. Differences between cohorts and frailty stages were assessed using Kruskal–Wallis tests with Mann–Whitney U post-hoc comparisons. Non-parametric methods were applied due to non-normal distributions, and analyses were restricted to cases with valid biomarker data.
Results
Valid biomarker data were available for 473 participants for pT217, Aβ42, Aβ40 and pT181, and for 355–356 for GFAP and NfL. Biomarker levels differed significantly across cohorts for all markers (all p < 0.001). Acutely hospitalised participants showed the highest rank distributions, followed by nursing home residents and ambulatory participants. Functional status differed markedly by cohort (χ²=515.225; p < 0.001), with ambulatory individuals predominantly autonomous, while hospitalised and institutionalised participants showed higher levels of moderate, severe or total dependency. Advanced frailty was associated with higher levels of pT217, pT181, GFAP and NfL.
Conclusions
Neurodegenerative biomarkers vary across clinical cohorts and vulnerability profiles. Acute hospitalisation is associated with the highest biomarker burden, and advanced frailty with increased pT217, pT181, GFAP and NfL. Interpretation should consider clinical setting and frailty status.
Key messages
• Neurodegenerative biomarkers differ significantly across clinical cohorts, with the highest levels observed in acutely hospitalised older adults, reflecting increased biological vulnerability.
• Advanced frailty is associated with elevated pT217, pT181, GFAP and NfL levels, highlighting the importance of considering frailty status when interpreting blood-based biomarkers of neurodegeneration.