Regional cerebral blood flow reflects both neurodegeneration and microvascular integrity across the Alzheimer's continuum

Abstract INTRODUCTION Alzheimer's disease (AD) typically involves both neurodegenerative and vascular pathologies, each associated with reductions in cerebral blood flow (CBF). However, it remains unclear whether vascular and neural contributions to regional CBF can be differentiated. METHODS Using 3D background‐suppressed arterial spin labeled perfusion magnetic resonance imaging, we evaluated regional CBF in a cohort of 257 participants across the AD continuum and assessed the impact of risk factors for both AD and small vessel disease (SVD) on regional CBF. RESULTS Vascular risk factors (VRFs) were associated with reduced CBF in normal‐appearing periventricular white matter, while amyloid positivity was associated with reduced CBF in the posterior cingulate cortex and precuneus. Putative SVD‐sensitive regions in white matter exhibited diagnosis‐related CBF changes comparable to those in typical AD cortical regions. DISCUSSION Spatial patterns of hypoperfusion may differentiate AD and VRF‐related effects on regional CBF. Our findings also support the contribution of SVD in AD pathogenesis. Highlights We used 3D background‐suppressed pCASL MRI to evaluate CBF across the AD continuum. Putative SVD‐sensitive regions in white matter exhibited diagnosis‐related CBF changes. AD and/or SVD risk correlated with reduced CBF in AD and/or SVD‐related regions. VRFs were associated with more widespread CBF reductions than amyloid positivity. Spatial patterns of hypoperfusion may differentiate AD and VRF‐related effects.