Cross-sectional Associations of β-Amyloid, Tau, and Cerebrovascular Biomarkers With Neurodegeneration in Probable Dementia With Lewy Bodies
Daniel Ferreira, Scott A. Przybelski, Timothy G. Lesnick, Christopher G. Schwarz, Patricia Diaz‐Galvan, Jonathan Graff‐Radford, Matthew L. Senjem, Julie A. Fields, David S. Knopman, David T. Jones, Rodolfo Savica, Tanis J. Ferman, Neill R. Graff‐Radford, Val J. Lowe, Clifford R. Jack, Ronald C. Petersen, Eric Westman, Bradley F. Boeve, Kejal Kantarci
Abstract
BACKGROUND AND OBJECTIVES: Although alpha-synuclein-related pathology is the hallmark of dementia with Lewy bodies (DLB), cerebrovascular and Alzheimer disease pathologies are common in patients with DLB. Little is known about the contribution of these pathologies to neurodegeneration in DLB. We investigated associations of cerebrovascular, β-amyloid, and tau biomarkers with gray matter (GM) volume in patients with probable DLB. METHODS: F-flortaucipir PET as markers of β-amyloid and tau, respectively. MRI was used to assess white matter hyperintensity (WMH) volume (a marker of cerebrovascular lesion load) and regional GM volume (a marker of neurodegeneration). We used correlations and analysis of covariance (ANCOVA) in the entire cohort and structural equation models (SEMs) in patients with DLB to investigate associations of WMH volume and regional β-amyloid and tau PET standardized uptake value ratios (SUVrs) with regional GM volume. RESULTS: ε4 allele were significant predictors of higher WMH volume, and WMH volume in turn was a significant predictor of GM volume in medial and orbital frontal cortices, insula, and inferior temporal cortex. By contrast, we observed 2 distinct paths for the fusiform cortex, with age having an effect through PiB and flortaucipir SUVr on one path and through WMH volume on the other path. DISCUSSION: Patients with probable DLB have widespread cortical atrophy, most of which is likely influenced by alpha-synuclein-related pathology. Although cerebrovascular, β-amyloid, and tau pathologies often coexist in probable DLB, their contributions to neurodegeneration seem to be region specific.