White Matter Hyperintensity Multispot Pattern Lesions and Cerebrovascular Amyloid Burden in Cerebral Amyloid Angiopathy

BACKGROUND: We investigated the relationship between white matter hyperintensity (WMH) multispot pattern lesions, a supporting magnetic resonance imaging marker of cerebral amyloid angiopathy (CAA), and positron emission tomography–based amyloid-β burden across a range of cerebrovascular amyloid deposition. METHODS: Twenty-one nondemented subjects (11 patients with probable CAA; median age, 71 [63–77] years; 82% males; and 10 healthy subjects; median age, 63.5 [61–68] years; 50% males) underwent brain magnetic resonance imaging and 11C-Pittsburgh compound B-positron emission tomography imaging. WMH multispot lesions were evaluated on FLAIR sequences. The association between whole cortex 11C-Pittsburgh compound B binding and WMH multispot lesions count was assessed using Kendall tau, adjusting for key markers of CAA through a hierarchical residualization approach. RESULTS: The unadjusted analysis showed a positive correlation between WMH multispot lesions count and whole cortex 11C-Pittsburgh compound B binding (tau-b=0.495; P =0.0017). Sequential adjustments for the presence of severe magnetic resonance imaging-visible perivascular spaces in the centrum semiovale, lobar cerebral microbleeds, age, and total WMH burden led to a progressive decline in correlation. The largest reduction occurred after adjusting for age (tau-b=0.307; P =0.0484) indicating its role as a potential confounder. In the fully adjusted model, the association remained significant (tau-b=0.316; P =0.0423), suggesting a partially independent relationship between WMH multispot lesions count and whole cortex amyloid burden. The results were consistent in a subanalysis within the probable CAA. CONCLUSIONS: This pilot study suggests a positive association between cerebrovascular amyloid deposition and WMH multispot lesions in CAA, with potential pathophysiological and clinical implications. These exploratory observations require confirmation in larger studies.