Clinician Hub - Cardiovascular Health and Brain Health

Overview

A robust evidence base now demonstrates that cardiovascular health is a major determinant of brain aging trajectories, influencing risk for stroke, vascular cognitive impairment, Alzheimer’s disease, and late-life psychiatric disorders. Together, these findings support a unified model in which cardiometabolic pathology accelerates both vascular brain injury and neurodegeneration, while optimal cardiovascular health slows both processes.

Epidemiologic Evidence Across the Lifespan

Global Brain Health Outcomes

Prospective cohort data from over 316,000 adults indicate that poor cardiovascular health more than doubles the risk of a composite neurologic outcome (stroke, dementia, or late-life depression) compared with optimal cardiovascular health (HR = 2.11).¹ This relationship has been validated across diverse populations.

Dementia Incidence and Cognitive Trajectories

In older adults, adherence to cardiovascular health metrics is associated with:

• Reduced dementia incidence

• Slower decline in global cognition and specific cognitive domains

• Dose–response benefit for each additional metric at ideal level²˒³

Remote cardiovascular health (i.e., midlife) appears to exert stronger predictive ability than recent measurements, suggesting critical prevention windows during midlife.⁴

Depression as a Neurovascular Outcome

Poor cardiovascular health increases risk of clinically significant depressive symptoms in older adults, independent of demographics and comorbidities.⁹Higher midlife cardiorespiratory fitness predicts both:

• Lower incident depression in later life

• Lower cardiovascular mortality among individuals who later develop depression¹⁰

Mechanistic Pathways

1. Vascular Pathways

Associations between cardiovascular health and reduced burden of:

• White matter hyperintensities (WMH)

• Lacunar infarcts

• Cerebral microbleeds

collectively support the model that favorable cardiovascular health reduces cerebral small-vessel disease, a major contributor to both cognitive impairment and late-life mood disorders.⁵˒⁶

2. Neurodegenerative Pathways

Cardiovascular health appears to mitigate neurodegeneration via:

• Lower serum neurofilament light chain (NfL), independent of WMH or structural vascular lesions⁷

• Slower brain atrophy across regions vulnerable to aging and Alzheimer's disease⁵

• Brain age estimates that appear “younger” relative to chronological age⁵˒⁶

3. Interaction With Genetic Risk

Genetic risk for metabolic dysfunction accelerates structural brain aging, but this effect is significantly attenuated among individuals with favorable cardiovascular health profiles.⁶ This suggests that behavioral and clinical risk-factor modification may partially offset inherited risk.

Population-Level Impact

Modeling data suggest that up to 35% of dementia cases could be prevented through elimination of modifiable cardiovascular risk factors.⁸ Declining dementia incidence in some nations is attributed partly to improvements in hypertension management, glycemic control, statin use, smoking cessation, and physical activity.

Clinical Implications for Practice

1. Integrating Cardiovascular and Cognitive Screening

Routine assessment of cardiovascular risk factors should be considered foundational to brain health prevention strategies in primary care, geriatrics, psychiatry, and behavioral health.

2. Interventions

Evidence-based targets include:

• Hypertension control

• Improved metabolic health (A1c, fasting glucose, lipids)

• Weight reduction

• Increased physical activity

• Smoking cessation

• Improved diet and sleep

The AHA’s Life’s Essential 8 offers a validated framework to operationalize these targets across preventive and specialty settings.¹¹˒¹²

3. Multi-domain Prevention Models

Trials such as multi-domain lifestyle interventions targeting blood pressure, diet, activity, and cognitive engagement suggest potential benefit in slowing cognitive decline in high-risk populations.

4. Relevance for Mental Health Clinicians

Given the bidirectional relationships among cardiovascular risk, depression, and cognitive decline, routine cardiometabolic monitoring is essential in psychiatric care—particularly in individuals using medications that may affect weight, glucose, or lipids.

References:

1. Clocchiatti-Tuozzo, S., Rivier, C. A., Renedo, D., et al. (2024). Life's Essential 8 and poor brain health outcomes in middle-aged adults. Neurology, 103(10), e209990. doi:10.1212/WNL.0000000000209990

2. Samieri, C., Perier, M. C., Gaye, B., et al. (2018). Association of cardiovascular health level in older age with cognitive decline and incident dementia. JAMA, 320(7), 657–664. doi:10.1001/jama.2018.11499

3. Samieri, C., Perier, M. C., Gaye, B., et al. (2018). Association of cardiovascular health level in older age with cognitive decline and incident dementia. JAMA, 320(7), 657–664. doi:10.1001/jama.2018.11499

4. Pase, M. P., Beiser, A., Enserro, D., et al. (2016). Association of ideal cardiovascular health with vascular brain injury and incident dementia. Stroke, 47(5), 1201–1206. doi:10.1161/STROKEAHA.115.012608

5. Huang, H., Wang, J., Dunk, M. M., et al. (2024). Association of cardiovascular health with brain age estimated using machine learning methods in middle-aged and older adults. Neurology, 103(2), e209530. doi:10.1212/WNL.0000000000209530

6. Li, Y., Laukka, E. J., Dekhtyar, S., et al. (2023). Association between behavioral, biological, and genetic markers of cardiovascular health and MRI markers of brain aging: A cohort study. Neurology, 100(1), e38–e48. doi:10.1212/WNL.0000000000201346

7. Dhana, A., DeCarli, C. S., Dhana, K., et al. (2025). Cardiovascular health and biomarkers of neurodegenerative disease in older adults. JAMA Network Open, 8(3), e250527. doi:10.1001/jamanetworkopen.2025.0527

8. Lazar, R. M., Howard, V. J., Kernan, W. N., et al. (2021). A primary care agenda for brain health: A scientific statement from the American Heart Association. Stroke, 52(6), e295–e308. doi:10.1161/STR.0000000000000367

9. van Sloten, T. T., Valentin, E., Climie, R. E., et al. (2023). Association of cardiovascular health with risk of clinically relevant depressive symptoms. JAMA Psychiatry, 80(4), 342–349. doi:10.1001/jamapsychiatry.2022.5056

10. Willis, B. L., Leonard, D., Barlow, C. E., et al. (2018). Association of midlife cardiorespiratory fitness with incident depression and cardiovascular death after depression in later life. JAMA Psychiatry, 75(9), 911–917. doi:10.1001/jamapsychiatry.2018.1467

11. Gorelick, P. B., Furie, K. L., Iadecola, C., et al. (2017). Defining optimal brain health in adults: A presidential advisory from the American Heart Association/American Stroke Association. Stroke, 48(10), e284–e303. doi:10.1161/STR.0000000000000148

12. Testai, F. D., Gorelick, P. B., Chuang, P. Y., et al. (2024). Cardiac contributions to brain health: A scientific statement from the American Heart Association. Stroke, 55(12), e425–e438. doi:10.1161/STR.0000000000000476

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