Vascular risk factors and cognitive decline: An integrated perspective from epidemiology to precision intervention

Abstract

Cognitive impairment and dementia have become a major global public health challenge. Traditionally attributed to Alzheimer’s disease pathology, cognitive decline is now recognized as being profoundly influenced and often driven by vascular factors, as evidenced by accumulating data over the past two decades. Based on recent high-quality evidence, this review systematically outlines the current epidemiological association between vascular risk factors and cognitive impairment. It delves deeply into the complex pathogenic mechanisms, ranging from macrovascular disease and cerebral small vessel disease to neurovascular unit dysfunction. The review critically evaluates the impact of traditional and novel management strategies for major vascular risk factors, such as hypertension, diabetes, and atrial fibrillation, on cognitive outcomes, and provides an in-depth analysis of multi-domain lifestyle intervention models represented by the Finnish FINGER study. Finally, this review critically points out the limitations of current research regarding population representativeness, biomarker translation, and intervention timing. It also looks forward to future directions integrating multi-omics data, developing precision risk stratification models, and conducting adaptive intervention trials. This review provides a comprehensive evidence-based synthesis, offering a forward-looking framework for a full-chain prevention system from risk screening to effective intervention centered on vascular health.

Keywords: Vascular risk factors; Cognitive decline; Vascular cognitive impairment; Cerebral small vessel disease; Mechanisms; Management

Core Tip: Vascular pathology is a core driver of cognitive decline (often coexisting with Alzheimer’s disease pathology). Midlife (40-65 years) is the critical prevention window. Key mechanisms include cerebral small vessel disease, blood-brain barrier disruption, neurovascular unit dysfunction, and neuroinflammation. Hypertension (including blood pressure variability) is the primary intervention target. Lifestyle interventions (e.g., FINGER model) are the most effective broad prevention strategy. Current challenges include diagnostic difficulties and insufficient personalized interventions. The core message is that maintaining vascular health maintains brain health.