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

Rune B Nielsen; Lærke Egefjord; Hugo Angleys; Kim Mouridsen; Michael Gejl; Arne Møller; Birgitte Brock; Hans Brændgaard; Hanne Gottrup; Jørgen Rungby; Simon Fristed Eskildsen; Leif Østergaard

doi:10.1016/j.jalz.2017.02.007

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

Rune B Nielsen, Lærke Egefjord, Hugo Angleys, Kim Mouridsen, Michael Gejl, Arne Møller, Birgitte Brock, Hans Brændgaard, Hanne Gottrup, Jørgen Rungby, Simon Fristed Eskildsen, Leif Østergaard

84 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Alzheimer's & dementia : the journal of the Alzheimer's Association
Vol/bind	13
Udgave nummer	10
Sider (fra-til)	1143–1153
Antal sider	11
ISSN	1552-5260
DOI	https://doi.org/10.1016/j.jalz.2017.02.007
Status	Udgivet - okt. 2017

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10.1016/j.jalz.2017.02.007

Citationsformater

Nielsen, R. B., Egefjord, L., Angleys, H., Mouridsen, K., Gejl, M., Møller, A., Brock, B., Brændgaard, H., Gottrup, H., Rungby, J., Eskildsen, S. F., & Østergaard, L. (2017). Capillary dysfunction is associated with symptom severity and neurodegeneration in Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association, 13(10), 1143–1153. https://doi.org/10.1016/j.jalz.2017.02.007

Nielsen, RB, Egefjord, L, Angleys, H, Mouridsen, K, Gejl, M, Møller, A, Brock, B, Brændgaard, H, Gottrup, H, Rungby, J, Eskildsen, SF & Østergaard, L 2017, 'Capillary dysfunction is associated with symptom severity and neurodegeneration in Alzheimer's disease', Alzheimer's & dementia : the journal of the Alzheimer's Association, bind 13, nr. 10, s. 1143–1153. https://doi.org/10.1016/j.jalz.2017.02.007

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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.",

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doi = "10.1016/j.jalz.2017.02.007",

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AU - Nielsen, Rune B

AU - Egefjord, Lærke

AU - Angleys, Hugo

AU - Mouridsen, Kim

AU - Gejl, Michael

AU - Møller, Arne

AU - Brock, Birgitte

AU - Brændgaard, Hans

AU - Gottrup, Hanne

AU - Rungby, Jørgen

AU - Eskildsen, Simon Fristed

AU - Østergaard, Leif

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N2 - 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.

AB - 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.

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

Abstract

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