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

97 Citations (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.

Original language	English
Journal	Alzheimer's & dementia : the journal of the Alzheimer's Association
Volume	13
Issue number	10
Pages (from-to)	1143–1153
Number of pages	11
ISSN	1552-5260
DOIs	https://doi.org/10.1016/j.jalz.2017.02.007
Publication status	Published - Oct 2017

Keywords

Journal Article

Access to Document

10.1016/j.jalz.2017.02.007

Cite this

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, vol. 13, no. 10, pp. 1143–1153. https://doi.org/10.1016/j.jalz.2017.02.007

@article{423c6766fb59481ca844b230c02dcaf1,

title = "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 (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 = "Journal Article",

author = "Nielsen, \{Rune B\} and L{\ae}rke Egefjord and Hugo Angleys and Kim Mouridsen and Michael Gejl and Arne M{\o}ller and Birgitte Brock and Hans Br{\ae}ndgaard and Hanne Gottrup and J{\o}rgen Rungby and Eskildsen, \{Simon Fristed\} and Leif {\O}stergaard",

year = "2017",

month = oct,

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

language = "English",

volume = "13",

pages = "1143–1153",

journal = "Alzheimer's \& dementia : the journal of the Alzheimer's Association",

issn = "1552-5260",

publisher = "Elsevier Inc",

number = "10",

}

TY - JOUR

T1 - Capillary dysfunction is associated with symptom severity and neurodegeneration in Alzheimer's disease

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

PY - 2017/10

Y1 - 2017/10

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.

KW - Journal Article

UR - https://www.scopus.com/pages/publications/85017188013

U2 - 10.1016/j.jalz.2017.02.007

DO - 10.1016/j.jalz.2017.02.007

M3 - Journal article

C2 - 28343848

SN - 1552-5260

VL - 13

SP - 1143

EP - 1153

JO - Alzheimer's & dementia : the journal of the Alzheimer's Association

JF - Alzheimer's & dementia : the journal of the Alzheimer's Association

IS - 10

ER -

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this