Capillary dysfunction is associated with symptom severity and neurodegeneration in Alzheimer's disease. Issue 10 (23rd March 2017)

• Record Type: Journal Article
• Authors: Nielsen, Rune B.; Egefjord, Lærke; Angleys, Hugo; Mouridsen, Kim; Gejl, Michael; Møller, Arne; Brock, Birgitte; Brændgaard, Hans; Gottrup, Hanne; Rungby, Jørgen; Eskildsen, Simon F.; Østergaard, Leif
• Is Part Of: Alzheimer's & dementia. Volume 13:Issue 10(2017)
• Page Start: 1143
• Page End: 1153
• Publication Date: 2017-03-23
• Subjects: Alzheimer's disease -- Magnetic resonance imaging (MRI) -- Perfusion imaging -- Capillary dysfunction -- Microvascular dysfunction -- Neurovascular dysfunction -- Capillary transit time heterogeneity (CTH) -- Relative transit time heterogeneity (RTH) -- Cerebral blood flow (CBF) -- Cerebral blood volume (CBV) -- Hypoxia -- Tissue oxygen tension (PtO2) -- Cortical thinning -- Neurodegeneration; Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1016/j.jalz.2017.02.007
• Languages: English
• ISSNs: 1552-5260

Abstract

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 (Pt O2 ). Results: At baseline, poor cognitive performance and regional cortical thinning correlated with lower CBF and CBV, with higher MTT and CTH and with low Pt O2 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. Highlights: 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.