Hypertension and cerebral blood flow in the development of Alzheimer's disease

Abstract INTRODUCTION We investigated the interactive associations between amyloid and hypertension on the entorhinal cortex (EC) tau and atrophy and the role of cerebral blood flow (CBF) as a shared mechanism by which amyloid and hypertension contribute to EC tau and regional white matter hyperintensities (WMHs). METHODS We analyzed data from older adults without dementia participating in the Add‐Tau study (NCT02958670, n = 138) or Alzheimer's Disease Neuroimaging Initiative (ADNI) ( n = 523) who had available amyloid‐positron emission tomography (PET), tau‐PET, fluid‐attenuated inversion recovery (FLAIR), and T1‐weighted magnetic resonance imaging (MRI). A subsample in both cohorts had available arterial spin labeling (ASL) MRI (Add‐Tau: n = 78; ADNI: n = 89). RESULTS The detrimental effects of hypertension on AD pathology and EC thickness were more pronounced in the Add‐Tau cohort. Increased amyloid burden was associated with decreased occipital gray matter CBF in the ADNI cohort. In both cohorts, lower regional gray matter CBF was associated with higher EC tau and posterior WMH burden. DISCUSSION Reduced cerebral perfusion may be one common mechanism through which hypertension and amyloid are related to increased EC tau and WMH volume. Highlights Hypertension is associated with increased entorhinal cortex (EC) tau, particularly in the presence of amyloid. Decreased cortical cerebral blood flow (CBF) is associated with higher regional white matter hyperintensity volume. Increasing amyloid burden is associated with decreasing CBF in the occipital lobe. MTL CBF and amyloid are synergistically associated with EC tau.