Higher educational attainment is associated with a lower burden of white matter hyperintensities (WMHs), partially explained by differences in vascular risk profiles, according to study findings published in Alzheimer’s & Dementia.

White matter hyperintensities are magnetic resonance imaging (MRI)-detectable markers of cerebral small vessel disease that are associated with cognitive decline, progression to mild cognitive impairment, and increased dementia risk. Although higher educational attainment is thought to protect against cognitive aging, it remains unclear whether this benefit is mediated by differences in cerebrovascular health, prompting researchers to examine the role of vascular risk factors in the relationship between education and WMH burden.

Researchers conducted a cross-sectional analysis using data from the National Alzheimer’s Coordinating Center, including 1443 participants aged 55 years and older with available MRI and vascular risk data. Participants had normal cognition or had diagnoses of mild cognitive impairment or Alzheimer disease. Education was measured as years of formal schooling completed. The researchers quantified WMH burden using automated segmentation of T1-weighted and fluid-attenuated inversion recovery MRI scans and normalized for intracranial volume. Analyses evaluated both total WMH volume and regional WMH burden across frontal, temporal, parietal, and occipital lobes.

At baseline, the mean age of the cohort was 74.3 years, and 59% of participants were women. The mean educational attainment was 15.1 years, though substantial differences were observed across racial and ethnic groups. Vascular risk factors were common: 47% of participants had hypertension, 50% had hypercholesterolemia, 16% had diabetes, and 60% had a body mass index (BMI) of 25 kg/m² or greater. Smoking history was reported by 40% of participants. The mean composite vascular risk score, which incorporated diabetes, hypertension, hypercholesterolemia, smoking, alcohol abuse, BMI, and blood pressure, was 2.7 out of a possible 8 points.

Higher educational attainment was consistently associated with a more favorable vascular risk profile. In adjusted regression models, education was inversely associated with diabetes, hypertension, hypercholesterolemia, BMI, smoking exposure, alcohol abuse, and systolic blood pressure (all P <0.001). Education was also significantly associated with lower cumulative vascular burden, as reflected by both the composite vascular risk score and a BMI-based atherosclerotic cardiovascular disease risk score.

Education was independently associated with lower WMH burden after adjusting for age, sex, race, and cognitive diagnosis. Each additional year of education was associated with a modest but significant reduction in total WMH volume (β=-0.05; P =.004). Region-specific analyses showed inverse associations across all lobes, with the strongest effects observed in the parietal and occipital regions.

Mediation analyses demonstrated that vascular risk factors partially mediated the relationship between education and WMH burden. The indirect effect of education on total WMH volume through the composite vascular risk score was significant (a*b=-0.02; P <.001), accounting for approximately 27% of the total association. Similar results were observed when vascular risk was indexed using the BMI-based cardiovascular risk score, which mediated 22% of the education-WMH relationship. No single vascular risk factor independently explained the mediation effect, suggesting that the pathway reflects cumulative vascular burden rather than an isolated risk factor.

Study limitations include a cross-sectional design, reduced statistical power in non-White subgroups, and reliance on binary vascular risk indicators.

“[O]ur findings offer a better understanding of how education protects the cerebrovascular system in aging populations and emphasize integrating educational equity and vascular risk prevention in public health strategies to mitigate cerebrovascular disease and slow cognitive aging,” the study authors concluded.

Disclosures: This research was supported by the National Institute on Aging of the National Institutes of Health, the Canadian Institutes of Health Research, the Fonds de Recherche du Québec—Santé, the Natural Sciences and Engineering Research Council of Canada, and Brain Canada. Please see the original reference for a full list of disclosures.