AbstractDiseases of the heart and brain are strongly linked to each other, and cardiac dysfunction is associated with cognitive decline and dementia. This link between cardiovascular disease and dementia offers opportunities for dementia prevention through prevention and treatment of cardiovascular risk factors and heart disease. Increasing evidence suggests the clinical utility of cardiac biomarkers as risk markers for structural brain changes and cognitive impairment. We propose the hypothesis that structural brain changes are the link between impaired cardiac function, as captured by blood‐based cardiac biomarkers, and cognitive impairment. This review provides an overview of the literature and illustrates emerging insights into the association of markers of hemodynamic stress (natriuretic peptides) and markers of myocardial injury (cardiac troponins) with imaging findings of brain damage and cognitive impairment or dementia. Based on these findings, we discuss potential pathophysiological mechanisms underlying the association of cardiac biomarkers with structural brain changes and dementia. We suggest testable hypotheses and a research plan to close the gaps in understanding the mechanisms linking vascular damage and neurodegeneration, and to pave the way for targeted effective interventions for dementia prevention. From a clinical perspective, cardiac biomarkers open the window for early identification of patients at risk of dementia, who represent a target population for preventive interventions targeting modifiable cardiovascular risk factors to avert cognitive decline and dementia.