Signature White Matter Hyperintensity Locations Associated With Vascular Risk Factors Derived From 15 653 Individuals

White matter hyperintensities (WMHs) of presumed vascular origin are common in the elderly and are associated with vascular risk factors. There is evidence that vascular risk factors, in particular hypertension, are associated with WMH in particular locations of the white matter. However, it remains unclear whether this is true for all risk factors and whether signature WMH locations differ between risk factors. We aimed to identify WMH locations associated with vascular risk factors in community-dwelling individuals.

We pooled cross-sectional data from 16 population-based cohorts (15 653 individuals; mean age, 64.2±11.8 years; 52.2% female) through the Meta VCI Map Consortium. We quantified associations between WMH volumes in 50 white matter regions and 6 vascular risk factors using linear mixed models. Analyses were corrected for age, sex, study site, and total WMH volume.

Hypertension (B=0.141; P<0.001), smoking (B=0.096; P<0.001), diabetes (B=0.059; P<0.001), and history of vascular disease (B=0.056; P=0.034) were significantly associated with higher total WMH volume, whereas obesity (B=0.023; P=0.139) and hypercholesterolemia (B=0.009; P=0.531) were not. After correcting for total WMH volume, hypertension was associated with WMH volume in 10 regions (ie, bilateral external capsule, superior longitudinal fasciculus, superior corona radiata, anterior limb of the internal capsule, left anterior corona radiata, and left superior fronto-occipital fasciculus), smoking (body corpus callosum), diabetes (genu corpus callosum), and obesity (left inferior fronto-occipital fasciculus), each with one region.

Hypertension has a signature WMH pattern, whereas associations between other vascular risk factors and regional WMH volumes seem to be mainly explained by a global increase in WMH rather than region-specific effects.