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

Abstract

Introduction: We 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.

Methods: Thirty-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 (P_tO₂).

Results: At baseline, poor cognitive performance and regional cortical thinning correlated with lower CBF and CBV, with higher MTT and CTH and with low P_tO₂ across the cortex. Cognitive decline over time was associated with increasing whole brain relative transit time heterogeneity (RTH = CTH/MTT).

Discussion: Our results confirm the importance of microvascular pathology in AD. Deteriorating microvascular hemodynamics may cause hypoxia, which is known to precipitate amyloid retention.

Keywords: Alzheimer's disease; Capillary dysfunction; Capillary transit time heterogeneity (CTH); Cerebral blood flow (CBF); Cerebral blood volume (CBV); Cortical thinning; Hypoxia; Magnetic resonance imaging (MRI); Microvascular dysfunction; Neurodegeneration; Neurovascular dysfunction; Perfusion imaging; Relative transit time heterogeneity (RTH); Tissue oxygen tension (P(t)O(2)).