Are Deep White Matter Hyperintensities Associated with Amyloid-Related Imaging Abnormalities in Patients with Alzheimer Disease Treated with Lecanemab?

BACKGROUND AND PURPOSE: Amyloid-related imaging abnormalities (ARIA) are common complications of antiamyloid immunotherapy for Alzheimer disease (AD). Identifying imaging biomarkers that predict ARIA risk may help guide treatment decisions. This study investigates the relationship between deep white matter hyperintensities (DWMH), perivascular spaces (PVS), and ARIA incidence in patients with AD treated with lecanemab.

MATERIALS AND METHODS: This retrospective cohort study included 27 ARIA-positive patients identified between November 2023 and November 2024, and 27 age- and sex-matched ARIA-negative controls. Baseline MRI was assessed for DWMH burden (Fazekas score) and PVS grades in the basal ganglia and centrum semiovale. Simple logistic regression was performed to evaluate associations between imaging markers and ARIA risk.

RESULTS: ARIA-positive patients had significantly higher Fazekas scores compared with ARIA-negative patients (1.37 versus 1.0; P = .0262), indicating a greater DWMH burden. PVS grades in the basal ganglia were numerically higher in ARIA-positive patients (1.81 versus 1.56, P = .0733) but did not reach statistical significance. Simple logistic regression identified the Fazekas score as a significant predictor of ARIA (OR: 2.812; 95% CI, 1.076–8.438; P = .0343). The area under the receiver operating characteristic curve for the model was 0.640 (95% CI, 0.492–0.788; P = .078).

CONCLUSIONS: Higher DWMH burden, as quantified by the Fazekas score, is significantly associated with ARIA risk in patients with AD treated with lecanemab. These findings suggest that DWMH may serve as a potential imaging biomarker for ARIA risk stratification. Larger studies incorporating additional vascular biomarkers, including cerebral amyloid angiopathy markers, are warranted to refine risk prediction models.