Rune B Nielsen1, Lærke Egefjord2, Hugo Angleys3, Kim Mouridsen3, Michael Gejl4, Arne Møller5, Birgitte Brock4, Hans Brændgaard6, Hanne Gottrup6, Jørgen Rungby7, Simon F Eskildsen3, Leif Østergaard8. 1. Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark. Electronic address: rbaeksager@cfin.au.dk. 2. Department of Biomedicine, Aarhus University, Aarhus, Denmark. 3. Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark. 4. Department of Biomedicine, Aarhus University, Aarhus, Denmark; Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark. 5. PET-Center, Department of Nuclear Medicine, Aarhus University Hospital, Aarhus, Denmark. 6. Dementia Clinic, Department of Neurology, Aarhus University Hospital, Aarhus, Denmark. 7. Department of Endocrinology, Bispebjerg University Hospital, Copenhagen, Denmark. 8. Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark; Department of Neuroradiology, Aarhus University Hospital, Aarhus, Denmark.
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.
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 ADpatients 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.
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