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

Table 1 Summary of core vascular risk factors, pathogenic mechanisms, biomarkers, and management strategies for cognitive decline

Vascular risk factor	Key pathogenic mechanisms	Neuroimaging biomarkers	Fluid biomarkers	Management strategies	Level of evidence
Hypertension	Large artery stiffness, CSVD, BBB disruption, neuroinflammation	WMH volume, lacunes, microbleeds, enlarged perivascular spaces	CSF/serum albumin ratio (BBB permeability), inflammatory markers	Intensive BP control (SBP < 120 mmHg); monitor BPV	Class A (SPRINT MIND trial and post-hoc analysis[16])
Diabetes	Insulin resistance, AGEs, microvascular complications, impaired β-amyloid clearance	WMH, hippocampal atrophy, cerebral microinfarcts	HbA1c, AGEs, insulin resistance markers	Glycemic control (early stage); metformin; multifactorial intervention	Class B (observational cohorts[58,59])
Atrial fibrillation	Cardioembolism, chronic hypoperfusion, systemic inflammation	Silent infarcts, WMH, cortical microinfarcts	NT-proBNP, hs-cTnT, D-dimer	Anticoagulation (DOACs/warfarin); rate/rhythm control	Class A (RCTs for stroke prevention[84,85])
Obesity/metabolic syndrome	Endothelial dysfunction, impaired neurovascular coupling, adipokine dysregulation	WMH, reduced CBF, microvascular rarefaction	Adipokines (leptin, adiponectin), IL-6, TNF-α	Multi-domain lifestyle intervention (FINGER model[80])	Class A (FINGER RCT[86])
Atherosclerosis	Large artery stenosis, hypoperfusion, embolic events	Carotid IMT, intracranial plaque, CBF reduction	LDL-C, hs-CRP, Lp-PLA2	Statins; antiplatelet therapy; lifestyle modification

CSVD: Cerebral small vessel disease; BBB: Blood-brain barrier; AGE: Advanced glycation end product; WMH: White matter hyperintensities; CBF: Cerebral blood flow; IMT: Intima-media thickness; HbA1c: Glycated hemoglobin; CSF: Cerebrospinal fluid; NT-proBNP: N-terminal pro-B-type natriuretic peptide; hs-cTnT: High-sensitivity cardiac troponin T; IL: Interleukin; TNF: Tumor necrosis factor; LDL-C: Low-density lipoprotein cholesterol; hs-CRP: High-sensitivity C-reactive protein; Lp-PLA2: Lipoprotein-associated phospholipase A2; BP: Blood pressure; SBP: Systolic blood pressure; BPV: Blood pressure variability; DOAC: Direct oral anticoagulant; SPRINT MIND: Systolic Blood Pressure Intervention Trial–Memory and Cognition in Decreased Hypertension.