A Novel Potential Pathway Linking Cardiac Diseases and Cognitive Dysfunction: Impaired Brain Glymphatic Function

ABSTRACT Growing evidence confirms that cardiac diseases and cognitive dysfunction are closely related. Multiple cardiac diseases have been identified as important risk factors for cognitive impairment and dementia. Notably, recent studies suggest that cardiac diseases are associated not only with vascular cognitive impairment but also with an increased risk of neurodegenerative disorders, including Alzheimer’s disease (AD). The mechanisms by which cardiac diseases contribute to cognitive impairment and dementia, particularly neurodegenerative cognitive impairment, remain unclear. Established mechanisms such as thromboembolism and cerebral hypoperfusion do not fully explain this association. Emerging data indicate that disrupted brain glymphatic function could serve as a potential intermediate pathway connecting cardiac diseases, neurodegeneration, and cognitive dysfunction. The brain glymphatic system represents a recently identified pathway responsible for clearing brain metabolic waste: Cerebrospinal fluid (CSF) enters the brain via perivascular spaces, exchanges with interstitial fluid, and eliminates metabolites. Normal cardiac pulsation is hypothesized to facilitate brain glymphatic circulation, as arterial pulsatility generated by cardiac cycles may drive perivascular CSF movement. This review integrates current evidence suggesting potential links between cardiac diseases, altered glymphatic function, and cognitive impairment. It also proposes a hypothetical mechanistic framework to explore how cardiac diseases might contribute to cognitive dysfunction. This work may provide a reference for subsequent mechanistic explorations and therapeutic target development aimed at cognitive impairment and dementia in patients with cardiac diseases.