Featured ArticleCapillary dysfunction is associated with symptom severity and neurodegeneration in Alzheimer's disease

•High cortical capillary transit time heterogeneity (CTH) correlates with poor cognitive performance.•High cortical CTH correlates with cortical thinning.•Increasing relative transit time heterogeneity over time correlates with cognitive decline.•The observed hemodynamic is consistent with cortical hypoxia in Alzheimer's disease (AD).•Capillary dysfunction may be a therapeutic target in AD.

IntroductionWe examined whether cortical microvascular blood volume and hemodynamics in Alzheimer's disease (AD) are consistent with tissue hypoxia and whether they correlate with cognitive performance and the degree of cortical thinning.MethodsThirty-two AD patients underwent cognitive testing, structural magnetic resonance imaging (MRI), and perfusion MRI at baseline and after 6 months. We measured cortical thickness, microvascular cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and capillary transit time heterogeneity (CTH) and estimated tissue oxygen tension (PtO2).ResultsAt baseline, poor cognitive performance and regional cortical thinning correlated with lower CBF and CBV, with higher MTT and CTH and with low PtO2 across the cortex. Cognitive decline over time was associated with increasing whole brain relative transit time heterogeneity (RTH = CTH/MTT).DiscussionOur results confirm the importance of microvascular pathology in AD. Deteriorating microvascular hemodynamics may cause hypoxia, which is known to precipitate amyloid retention.