WHITE MATTER HYPERINTENSITIES AND VASCULAR RISK FACTORS IN ALZHEIMER’S DISEASE

Background – White matter hyperintensities (WMHs) are common MRI findings in older adults, traditionally interpreted as markers of cerebral small vessel disease (SVD). In Alzheimer’s disease, however, WMHs may reflect not only vascular pathology but also intrinsic AD-related processes, making it important to clarify the role of cardiovascular risk factors (CVFs) in their development. Aim of the study – To investigate whether AD patients with WMHs display a higher prevalence of CVFs compared to those without and to explore the associations with other neuroimaging markers of cerebrovascular events. Methods – A retrospective cross-sectional study was conducted on 138 AD patients from Baggiovara Hospital (2010-2025) who had undergone high-resolution 3T MRI scan. Demographic, clinical, laboratory, and imaging data, including CSF biomarkers and ApoE status, were collected. MRI scans were visually assessed for WMHs rated according to the Boston criteria 2.0 for Cerebral Amyloid Angiopathy, Fazekas scores, and neuroimaging markers of presumed vascular origin including cerebral microbleeds (CBM), cortical superficial siderosis (cSS), and enlarged perivascular spaces (EPVS). Patients were categorized into WMH and non-WMH groups and compared using statistical tests and logistic regression. Results – WMHs were detected in 78 patients (56.5%). Compared to non-WMH patients, this group was older (p<0.001) and had disease onset at an older age (p<0.001), and showed significantly lower CSF Aβ42/40 ratio (p=0.035). Smoking was the only CVF significantly higher in the WMH group (p=0.010) whereas there were no differences in prevalence of diabetes, hypertension, dyslipidemia, and atrial fibrillation. As expected, other neuroimaging markers of presumed vascular origin were consistently more prevalent in the WMH group, including CMB (p<0.001), cSS (p=0.011), and EPVS (p=0.006). Univariate analysis confirmed significant associations of WMHs with age, smoking, lower Aβ42, CMB, EPVS, and Fazekas score. In multivariate regression, only older age (OR=1.098; p=0.005), EPVS (OR=3.309; p=0.038), and higher Fazekas scores (OR=53.520; p<0.001) remained independent predictors. Discussion – Our findings indicate that WMHs in AD should not be interpreted as a mere consequence of systemic CVFs, but rather as a complex phenomenon arising from the interaction between AD pathology, neuroaging, neuroinflammation, and impairments in perivascular clearance.