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REVIEW ARTICLE

Minds and hearts: Cardio-neural crosstalk in cardiovascular and neurodegenerative diseases

Ata Amro1 ,  Djamel Lebeche1,2,3*
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1 Department of Medicine, College of Medicine, The University of Tennessee Health Science Center, Memphis, Tennessee, United States of America
2 Department of Physiology, College of Medicine, The University of Tennessee Health Science Center, Memphis, Tennessee, United States of America
3 Neuroscience Institute, College of Medicine, The University of Tennessee Health Science Center, Memphis, Tennessee, United States of America
Brain & Heart, 025270033 https://doi.org/10.36922/BH025270033
Received: 30 June 2025 | Revised: 15 January 2026 | Accepted: 22 January 2026 | Published online: 20 February 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

With increasing life expectancy, the prevalence of age-related cardiovascular diseases—including hypertension, atherosclerosis, atrial fibrillation, and heart failure—and neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease (PD) continues to rise. Emerging evidence indicates that the heart and brain are linked through complex, bidirectional pathways in which cardiovascular pathology can accelerate neurodegeneration, while neurodegenerative processes can precipitate or exacerbate cardiovascular dysfunction. This review critically appraises current knowledge on cardio-neural crosstalk, distinguishing well-established associations (e.g., hypertension and dementia) from more speculative mechanisms (e.g., receptor changes in ischemic PD). We integrate epidemiological findings with mechanistic insights, highlighting inflammation, hypoperfusion, blood–brain barrier disruption, autonomic dysfunction, and amyloid biology as convergent pathways. To enhance clarity, we summarize evidence strength in expanded tables and figures, including epidemiological hazard ratios, mechanistic pathways, and confidence grading. The main contribution of this review is to provide a structured synthesis of robust and emerging evidence on the bidirectional heart–brain axis, identifying gaps that limit causal inference. We emphasize future directions such as longitudinal biomarker studies, interventional trials repurposing cardiovascular therapies for neuroprotection, and systems biology approaches to integrate cardiovascular and neurodegenerative omics data. By consolidating current evidence and outlining actionable research priorities, this review aims to inform both clinical practice and translational research in cardio-neural disease.

Graphical abstract
Keywords
Cardio-neural crosstalk
Heart–brain axis
Cardiovascular diseases
Neurodegeneration
Alzheimer’s disease
Parkinson’s disease
Heart failure
Funding
Djamel Lebeche is partially supported by startup funds from the University of Tennessee Health Science Center.
Conflict of interest
Djamel Lebeche is an Editorial Board Member of this journal but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.
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Brain & Heart, Electronic ISSN: 2972-4139 Published by AccScience Publishing
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