AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Cardiac Biomarkers as Predictors of Cognitive Decline and Incident Dementia: A Systematic Review and Meta-Analysis of the Heart-Brain Connection
By MURUGAVEL D, Andanappa A, Phani Ajay GGS et al.
Introduction: The heart-brain connection is increasingly recognized, yet few meta-analyses have systematically quantified how cardiac biomarkers predict cognitive outcomes. This systematic review and meta-analysis synthesizes available evidence to determine whether circulating cardiac biomarkers independently predict cognitive decline and incident dementia, addressing a critical gap in cardiovascular brain health research. Methods: We systematically searched PubMed, Embase, and Cochrane (inception-June 2026) for prospective studies examining cardiac biomarkers (e.g., NT-proBNP, troponin) and cognitive decline or incident dementia. Two reviewers independently screened, extracted data, and assessed bias (QUIPS tool). Random-effects meta-analyses pooled hazard ratios using Stata 18.0. Results: We screened 1,847 citations; 18 prospective studies (78,432 participants; 8,214 incident dementia cases; mean follow-up 8.3 years) met inclusion criteria. Twelve studies reported NT-proBNP (n = 54,126), nine reported hs-cTnT/hs-cTnI (n = 43,897), and four reported GDF-15 (n = 12,405). Meta-analysis showed higher NT-proBNP associated with incident dementia (pooled adjusted HR per log increase: 1.32; 95% CI: 1.21-1.44; p < 0.001; I ² = 62%; τ ² = 0.031) and cognitive decline (HR: 1.28; 95% CI: 1.18-1.39; p < 0.001; I ² = 58%). For hs-cTnT, dementia HR was 1.18 (95% CI: 1.09-1.28; p < 0.001; I ² = 41%); for hs-cTnI, HR was 1.09 (95% CI: 0.98-1.21; p = 0.11; I ² = 29%). Excluding four high-bias studies (n = 12,847) yielded similar NT-proBNP HR: 1.28 (95% CI: 1.17-1.40). In subgroups, associations were stronger among CVD-prevalent cohorts (HR: 1.45; 95% CI: 1.29-1.63) vs community-based (HR: 1.21; 95% CI: 1.12-1.31). Publication bias was suggested for NT-proBNP (Egger’s p = 0.04). GDF-15 was not significant (HR: 1.07; 95% CI: 0.95-1.20; I ² = 33%). Conclusion: Elevated NT-proBNP and hs-cTnT independently predict dementia and cognitive decline, positioning cardiac biomarkers as promising tools for heart-brain risk stratification. These findings strengthen the cardiovascular contribution to brain aging. GDF-15 was not significant. Routine incorporation of such biomarkers into clinical practice could enable earlier dementia risk detection.