The Heart-Brain-Emotion Axis in aging: An integrated framework linking cardiovascular dysfunction, emotional...

Population aging is accompanied by a parallel increase in cardiovascular disease (CVD), vascular cognitive impairment (VCI), and dementia, highlighting the urgent need to better understand the complex interactions linking cardiovascular, cognitive, and emotional health. Growing evidence suggests that cardiovascular dysfunction, emotional dysregulation, and cognitive decline are not isolated conditions but interconnected manifestations of shared vascular, inflammatory, neurohumoral, metabolic, and behavioral processes that progressively interact throughout aging. In this review, we examine current evidence supporting the Heart-Brain Axis and expand this concept into an integrated Heart-Brain-Emotion Axis, providing a comprehensive framework to explain the bidirectional relationships among cardiovascular dysfunction, emotional disturbances, and cognitive impairment. We discuss the major mechanisms underlying these interactions, including endothelial dysfunction, cerebral hypoperfusion, chronic low-grade inflammation, oxidative stress, autonomic imbalance, neuroendocrine dysregulation, and psychosocial factors such as depression, anxiety, chronic stress, and social isolation. Attention is given to the reciprocal amplification loops through which dysfunction in one domain may propagate across interconnected biological networks, increasing vulnerability to emotional and cognitive deterioration. Finally, we discuss the clinical implications of this integrated model, emphasizing the importance of early cardiovascular and cognitive screening, multidomain preventive approaches, personalized interventions, and the incorporation of cognitive and emotional assessment into cardiac rehabilitation programs. Recognizing the Heart-Brain-Emotion Axis may facilitate earlier identification of at-risk individuals and support more effective strategies to preserve both cardiovascular and brain health across the aging trajectory. SUMMARY: A growing body of evidence indicates that cardiovascular, emotional, and cognitive alterations should not be considered isolated phenomena but rather interconnected manifestations of a multisystem aging process. Age-related decline appears to arise from reciprocal interactions among cardiovascular, cerebrovascular, neural, and psychosocial mechanisms, whereby dysfunction in one domain propagates through interconnected biological networks, progressively amplifying vulnerability across the others. Shared pathophysiological pathways-including chronic low-grade inflammation, oxidative stress, autonomic dysfunction, neurohumoral imbalance, metabolic disturbances, and adverse lifestyle factors-simultaneously affect cardiovascular, brain, and emotional health, generating self-reinforcing feedback loops that accelerate functional decline. Within this framework, cardiovascular dysfunction contributes to cognitive impairment not only through vascular and neurovascular injury but also by influencing emotional well-being. Conversely, emotional dysregulation, including depression, anxiety, impaired stress adaptation, and reduced emotional resilience, can aggravate cardiovascular dysfunction through behavioral and physiological mechanisms, further compromising cognitive function. These reciprocal relationships support the concept of an integrated Heart-Brain-Emotion Axis, in which cardiovascular dysfunction, emotional dysregulation, and cognitive impairment interact dynamically throughout the aging trajectory. Viewing aging through this integrative framework provides a broader understanding of the mechanisms underlying functional decline and highlights the need for multidomain preventive strategies and personalized interventions. Cardiac rehabilitation may represent an ideal translational model by integrating cardiovascular risk management with cognitive and emotional interventions, thereby promoting healthy brain aging, preserving functional independence, and improving quality of life.