Cardiac output as a potential risk factor for abnormal brain aging

Abstract

Heart failure has served as a clinically useful model for understanding how cardiac dysfunction is associated with neuroanatomic and neuropsychological changes in aging adults, theoretically because systemic hypoperfusion disrupts cerebral perfusion, contributing to clinical brain injury. This review summarizes more recent data suggesting that subtle cardiac dysfunction or low normal levels of cardiac function, as quantified by cardiac output, are related to cognitive and neuroimaging markers of abnormal brain aging in the absence of heart failure or severe cardiomyopathy. Additional work is required, but such associations suggest that reduced cardiac output may be a risk factor for Alzheimer's disease (AD) and abnormal brain aging through the propagation or exacerbation of neurovascular processes, microembolism due to thrombosis, and AD neuropathological processes. Such mechanistic pathways are discussed in the context of a theoretical model that posits a direct pathway of injury between cardiac output and abnormal brain aging (i.e., reduced systemic blood flow disrupts cerebral blood flow homeostasis), contributing to clinical brain injury, independent of shared risk factors for both cardiac dysfunction and abnormal brain aging.

Fig. 1

Working theoretical model accounting for complex relations between reduced cardiac output and abnormal brain aging. A) There are established shared environmental and genetic risk factors that contribute to reduced cardiac output and abnormal brain aging. B) The model, as identified by the grey shadowed components, posits that reduced cardiac output creates a direct pathway of injury for the brain, independent of shared risk factors, in which reduced systemic blood flow alters cerebral blood flow homeostasis. This pathway accounts, in part, for previously reported relations between cardiac function and abnormal cognitive aging (e.g., executive dysfunction [37], WMHs [39], reduced brain volume [41]). C) However, a second plausible mechanism exists in which some epiphenomenon may account for previously reported associations between lower levels of cardiac output and abnormal brain aging. That is, that there may be intermediate pathways, such as vascular stiffness or neurohumoral factors, which contribute to both reduced cardiac output and abnormal brain aging.