Targeting Shared Risk Pathways to Prevent Stroke, Dementia, and Depression

By Rene Pretorius

April 23, 2025

This review examines a systematic study identifying 17 modifiable risk factors linked to stroke, dementia, and late-life depression (LLD) through shared risk pathways. Published in Journal of Neurology, Neurosurgery & Psychiatry (2025), the research offers critical insights for health policy executives and pharmaceutical leaders. By targeting shared risk pathways, stakeholders can promote healthy aging and build cost-effective healthcare systems. The study’s findings provide an evidence-based foundation for preventive strategies, addressing the rising burden of age-related brain diseases.

Background: The Need for Targeting Shared Modifiable Risk Pathways

Neurological and mental disorders account for a significant portion of the global disease burden. Stroke and dementia rank among the top causes of disability in older adults, while late-life depression (LLD) exacerbates healthcare challenges. The World Health Organization (WHO) emphasizes that modifying risk factors—such as hypertension, smoking, and sedentary lifestyles—can prevent up to 40% of dementia cases and reduce stroke incidence. Aging populations strain healthcare systems, with costs projected to exceed $1 trillion annually by 2050 for dementia alone. Current tools, like cardiovascular risk scores, often overlook shared risk pathways across brain diseases. This gap underscores the urgent need for holistic, cost-effective interventions targeting shared modifiable risk pathways to promote brain health.

Main Results: Key Modifiable Risk Factors for Brain Health

The systematic review analyzed 59 meta-analyses, identifying 17 modifiable risk factors for brain health. These factors influence stroke, dementia, and LLD, offering opportunities for integrated prevention.

  • High Blood Pressure: Hypertension (≥140/90 mm Hg) showed the strongest effect, with a relative risk (RR) of 2.68 for stroke and 1.20 for dementia. Managing blood pressure could significantly reduce disease incidence.

  • Kidney Function: Severe kidney disease (eGFR <30 mL/min/1.73 m²) increased stroke risk (RR: 1.70) and dementia risk (RR: 1.91). Early interventions targeting kidney health may yield broad benefits.

  • Smoking: Current smoking raised stroke risk (RR: 1.54–1.64) and dementia risk (RR: 1.27–1.30). Smoking cessation programs could lower disease burden.

  • Physical Activity: Moderate to high physical activity reduced stroke risk (RR: 0.64–0.85) and dementia risk (RR: 0.63–0.80). Exercise programs are cost-effective for prevention.

  • Diet: Adherence to AHA-recommended diets, like DASH, lowered stroke and dementia risks. Nutritional interventions offer scalable solutions.

  • Social Engagement: Social isolation increased stroke risk (RR: 1.32) and dementia risk (RR: 1.23–1.58). Community-based programs can enhance brain health.

  • Other Factors: Cognitive activity (RR: 0.61 for dementia), sleep quality (RR: 1.47–1.51 for insomnia), and stress (RR: 1.33–1.44) also showed significant effects. Holistic interventions addressing these factors can amplify impact.

The study calculated disability-adjusted life year (DALY)-weighted effect sizes, revealing shared risk pathways. Addressing one factor, like hypertension, may reduce risks across all three conditions, maximizing preventive impact.

Conclusion: Leveraging Shared Risk Pathways for Cost-Effective Healthcare and Healthy Aging

This study underscores the power of shared risk pathways in addressing modifiable risk factors for brain health. By targeting common risks like hypertension, smoking, and low physical activity, health policy executives can reduce the incidence of stroke, dementia, and LLD simultaneously. These shared pathways enable cost-effective interventions, potentially saving billions annually, with dementia care costs alone projected to reach $600 billion in the U.S. by 2030. Tools like the Brain Care Score, built on these findings, guide precise prevention strategies. Pharmaceutical leaders can prioritize therapies for hypertension and kidney health, while community programs promoting exercise, healthy diets, and social engagement offer scalable solutions. By focusing on shared risk pathways, stakeholders can foster healthy aging, alleviate disease burden, and create sustainable healthcare systems.

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