Progressive White Matter Injury in Preclinical Dutch Cerebral Amyloid Angiopathy
Zahra Shirzadi, Wai‐Ying Wendy Yau, Stephanie A. Schultz, Aaron P. Schultz, Matthew R. Scott, Maged Goubran, Parisa Mojiri‐Forooshani, Nelly Joseph‐Mathurin, Kejal Kantarci, Greg M. Preboske, Marieke J.H. Wermer, Clifford R. Jack, Tammie L.S. Benzinger, Kevin Taddei, Hamid R. Sohrabi, Reisa A. Sperling, Keith A. Johnson, Randall J. Bateman, Ralph N. Martins, Steven M. Greenberg, Jasmeer P. Chhatwal, DIAN Investigators
Abstract
Autosomal-dominant, Dutch-type cerebral amyloid angiopathy (D-CAA) offers a unique opportunity to develop biomarkers for pre-symptomatic cerebral amyloid angiopathy (CAA). We hypothesized that neuroimaging measures of white matter injury would be present and progressive in D-CAA prior to hemorrhagic lesions or symptomatic hemorrhage. In a longitudinal cohort of D-CAA carriers and non-carriers, we observed divergence of white matter injury measures between D-CAA carriers and non-carriers prior to the appearance of cerebral microbleeds and >14 years before the average age of first symptomatic hemorrhage. These results indicate that white matter disruption measures may be valuable cross-sectional and longitudinal biomarkers of D-CAA progression. ANN NEUROL 2022;92:358-363.