Biological Aging for Risk Prediction of First-Ever Intracerebral Hemorrhage and Cerebral Infarction in Advanced Age

Background and objectives: successful interventions to prevent cerebrovascular disease and stroke require early identification of persons at risk before clinical manifestation of disease. The literature remains to be sparse on accessible plasma-based biomarkers for monitoring brain health and cerebrovascular disease in advanced age. We assessed the predictive value of biological age (BA) as an early indicator for cerebrovascular disease and risk of first-ever intracerebral hemorrhage (ICH) and cerebral infarction (CI) in advanced age and compared these relationships with chronological age (CA) and commonly used biomarkers including tau and A ss 40 and A ss 42. Methods: The study included Individuals who consented for blood draw and follow-up. We computed biological age using structural equation modelling. The criteria for the biomarkers included their representability of the various body systems; their availability in the Rotterdam study and their prehypothesized reflection of aging in other populations. The algorithm integrates biomarkers that represent six body systems involved in overall cerebrovascular health including metabolic function, cardiac function, lung function, kidney function, liver function, immunity, and inflammation. Time to event analysis was conducted using Cox-regression models. Prediction analysis was conducted using Harrel's C and Area under the receiver operating characteristic curve. Results: The sample included a total of 1699 individuals at baseline followed up over a median of 11 years. During a period of 15, 780 and 16, 172 person-years, a total of 17 first-ever intracerebral hemorrhage and 83 cerebral infarction cases occurred. In time-to-event analysis, BA showed higher magnitude of associations with ICH compared to CA (HRBA-ICH: 2.30, 95% CI: 1.20, 4.30; HRCA-ICH: 1.40, 95% CI: 0.76, 2.53) and higher precision with CI (HRBA-CI: 1.30, 95% CI: 1.01,1.75; HR(CA-CI:)1.90, 95% CI: 1.48, 2.66). BA outperformed CA for prediction of ICH (AUC: 0.68 vs 0.53; Harrel's C: 0.72 vs 0.53) and for CI (AUC:0.63 vs 0.62; Harrel's C: 0.68 vs 0.67). Conclusions: Biological aging (delta biological aging) based on integrated physiology biomarkers provides a novel tool for monitoring and identification of persons at highest risk of cerebrovascular disease in advanced age with varying degrees of precision and magnitude for stroke subtypes. These variations are likely related to differences in pathophysiology of intracerebral hemorrhage and cerebral infarction. Wider validation and applicability require extension of these findings in other comparable samples and in clinical settings. (c) 2022 Elsevier Inc. All rights reserved.