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

Alzheimers Dement. 2017 Oct;13(10):1143-1153. doi: 10.1016/j.jalz.2017.02.007. Epub 2017 Mar 23.

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 (PtO2).

Results: At 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).

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)).

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / complications*
  • Alzheimer Disease / diagnostic imaging
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / pathology
  • Cerebrovascular Circulation / physiology*
  • Cognitive Dysfunction / diagnostic imaging
  • Cognitive Dysfunction / etiology*
  • Female
  • Hemodynamics / physiology*
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging
  • Male
  • Microvessels / pathology
  • Microvessels / physiopathology
  • Middle Aged
  • Neurodegenerative Diseases / diagnosis
  • Neurodegenerative Diseases / etiology*
  • Neuropsychological Tests
  • Perfusion