?-amyloid influences the relationship between cortical thickness and vascular load

Introduction: Cortical thickness has been proposed as a biomarker of Alzheimer�s disease related neurodegeneration, but the nature of its relationship with amyloid (A?) deposition and white matter hyperintensity volume (WMHV) in cognitively normal adults is unclear. Methods: We investigated the influences of A?-status (negative/positive) and WMHV on cortical thickness in 408 cognitively normal adults aged 69.2-71.9 years who underwent 18F-Florbetapir PET and structural MRI. Two previously defined Alzheimer�s disease cortical signature regions and the major cortical lobes were selected as regions of interest for cortical thickness. Results: Higher white matter hyperintensity volume, but not A?-status, predicted lower cortical thickness across all participants, in all regions of interest. Conversely, when A?-positive participants were considered alone, higher white matter hyperintensity volume predicted higher cortical thickness in a temporal Alzheimer�s disease-signature region. Discussion: WMHV may differentially influence cortical thickness depending on the presence or absence of ?-amyloid, potentially reflecting different pathological mechanisms