Systemic Extracerebral Atherosclerotic Burden and Dementia Risk After Incident Stroke

Stroke survivors are at increased risk of dementia, but clinically accessible markers of risk heterogeneity remain limited. Previous studies have largely examined atherosclerotic disease in individual vascular beds rather than the overall burden of systemic extracerebral atherosclerosis.

We included UK Biobank participants without stroke at baseline who subsequently developed incident stroke and remained under follow-up and dementia-free 1 year after the index event. Extracerebral atherosclerotic vascular disease (ECAVD) was evaluated according to its overall presence, the number of affected vascular beds, and the mutually adjusted contributions of carotid artery stenosis, coronary heart disease (CHD), and peripheral artery disease. Fine-Gray subdistribution hazard models were used with death treated as a competing event. Missing covariate data were addressed using multiple imputation.

Among 9571 participants, 584 developed all-cause dementia during follow-up. ECAVD was associated with a higher risk of dementia (subdistribution hazard ratio [sHR], 1.38; 95% confidence interval [CI] 1.13-1.68; p = 0.0014). The adjusted 5-year risks were 4.4% and 3.2% in participants with and without ECAVD, respectively, and the corresponding 10-year risks were 11.1% and 8.1%. Compared with no affected vascular beds, involvement of 1 vascular bed was associated with a higher dementia risk (sHR, 1.41; 95% CI 1.15-1.72), whereas the estimate for ≥ 2 affected beds was not statistically significant (sHR, 1.19; 95% CI 0.76-1.87). The per-category trend was significant (sHR, 1.24; 95% CI 1.07-1.45). In mutually adjusted analyses, CHD was associated with dementia (sHR, 1.42; 95% CI 1.13-1.78), whereas peripheral artery disease and carotid artery stenosis were not. No significant interaction was observed by stroke subtype or dementia subtype. Lipid-adjustment and complete-case analyses yielded similar results.

ECAVD was associated with a higher risk of all-cause dementia diagnosed more than 1 year after incident stroke. ECAVD may provide a practical indicator of cumulative systemic vascular burden and long-term cognitive risk, although vascular-bed count findings should be interpreted cautiously.