Capillary function progressively deteriorates in prodromal Alzheimer’s disease: A longitudinal MRI perfusion study

Lasse Stensvig Madsen; Rune Bæksager Nielsen; Peter Parbo; Rola Ismail; Irene Klærke Mikkelsen; Hanne Gottrup; Leif Østergaard; David J Brooks; Simon Fristed Eskildsen

doi:10.1016/j.nbas.2022.100035

Capillary function progressively deteriorates in prodromal Alzheimer’s disease: A longitudinal MRI perfusion study

Lasse Stensvig Madsen^*, Rune Bæksager Nielsen, Peter Parbo, Rola Ismail, Irene Klærke Mikkelsen, Hanne Gottrup, Leif Østergaard, David J Brooks, Simon Fristed Eskildsen

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

11 Citationer (Scopus)

Abstract

Cardiovascular risk factors are associated with the development of Alzheimer’s disease (AD), and increasing evidence suggests that cerebral microvascular dysfunction plays a vital role in the disease progression. Using magnetic resonance imaging, we investigated the two-year changes of the cerebral microvascular blood ﬂow in 11 mild cognitively impaired (MCI) patients with prodromal AD compared to 12 MCI patients without evidence of AD and 10 cognitively intact age-matched controls. The pAD-MCI patients displayed widespread deterioration in microvascular cerebral perfusion associated with capillary dysfunction. No such changes were observed in the other two groups, suggesting that the dysfunction in capillary perfusion is linked to the AD pathophysiology. The observed capillary dysfunction may limit local oxygenation in AD leading to downstream bamyloid aggregation, tau hyperphosphorylation, neuroinﬂammation and neuronal dysfunction. The ﬁndings are in agreement with the capillary dysfunction hypothesis of AD, suggesting that increasing heterogeneity of capillary blood ﬂow is a primary pathological event in AD.

Originalsprog	Engelsk
Artikelnummer	100035
Tidsskrift	Aging Brain
Vol/bind	2
Antal sider	9
ISSN	2589-9589
DOI	https://doi.org/10.1016/j.nbas.2022.100035
Status	Udgivet - jan. 2022

Emneord

Alzheimer's disease
Capillary dysfunction
Magnetic resonance imaging
Mild cognitive impairment
Perfusion

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title = "Capillary function progressively deteriorates in prodromal Alzheimer{\textquoteright}s disease: A longitudinal MRI perfusion study",

abstract = "Cardiovascular risk factors are associated with the development of Alzheimer's disease (AD), and increasing evidence suggests that cerebral microvascular dysfunction plays a vital role in the disease progression. Using magnetic resonance imaging, we investigated the two-year changes of the cerebral microvascular blood flow in 11 mild cognitively impaired (MCI) patients with prodromal AD compared to 12 MCI patients without evidence of AD and 10 cognitively intact age-matched controls. The pAD-MCI patients displayed widespread deterioration in microvascular cerebral perfusion associated with capillary dysfunction. No such changes were observed in the other two groups, suggesting that the dysfunction in capillary perfusion is linked to the AD pathophysiology. The observed capillary dysfunction may limit local oxygenation in AD leading to downstream β-amyloid aggregation, tau hyperphosphorylation, neuroinflammation and neuronal dysfunction. The findings are in agreement with the capillary dysfunction hypothesis of AD, suggesting that increasing heterogeneity of capillary blood flow is a primary pathological event in AD.",

keywords = "Alzheimer's disease, Capillary dysfunction, Magnetic resonance imaging, Mild cognitive impairment, Perfusion",

author = "Madsen, \{Lasse Stensvig\} and Nielsen, \{Rune B{\ae}ksager\} and Peter Parbo and Rola Ismail and Mikkelsen, \{Irene Kl{\ae}rke\} and Hanne Gottrup and Leif {\O}stergaard and Brooks, \{David J\} and Eskildsen, \{Simon Fristed\}",

year = "2022",

month = jan,

doi = "10.1016/j.nbas.2022.100035",

language = "English",

volume = "2",

journal = "Aging Brain",

issn = "2589-9589",

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TY - JOUR

T1 - Capillary function progressively deteriorates in prodromal Alzheimer’s disease

T2 - A longitudinal MRI perfusion study

AU - Madsen, Lasse Stensvig

AU - Nielsen, Rune Bæksager

AU - Parbo, Peter

AU - Ismail, Rola

AU - Mikkelsen, Irene Klærke

AU - Gottrup, Hanne

AU - Østergaard, Leif

AU - Brooks, David J

AU - Eskildsen, Simon Fristed

PY - 2022/1

Y1 - 2022/1

N2 - Cardiovascular risk factors are associated with the development of Alzheimer's disease (AD), and increasing evidence suggests that cerebral microvascular dysfunction plays a vital role in the disease progression. Using magnetic resonance imaging, we investigated the two-year changes of the cerebral microvascular blood flow in 11 mild cognitively impaired (MCI) patients with prodromal AD compared to 12 MCI patients without evidence of AD and 10 cognitively intact age-matched controls. The pAD-MCI patients displayed widespread deterioration in microvascular cerebral perfusion associated with capillary dysfunction. No such changes were observed in the other two groups, suggesting that the dysfunction in capillary perfusion is linked to the AD pathophysiology. The observed capillary dysfunction may limit local oxygenation in AD leading to downstream β-amyloid aggregation, tau hyperphosphorylation, neuroinflammation and neuronal dysfunction. The findings are in agreement with the capillary dysfunction hypothesis of AD, suggesting that increasing heterogeneity of capillary blood flow is a primary pathological event in AD.

AB - Cardiovascular risk factors are associated with the development of Alzheimer's disease (AD), and increasing evidence suggests that cerebral microvascular dysfunction plays a vital role in the disease progression. Using magnetic resonance imaging, we investigated the two-year changes of the cerebral microvascular blood flow in 11 mild cognitively impaired (MCI) patients with prodromal AD compared to 12 MCI patients without evidence of AD and 10 cognitively intact age-matched controls. The pAD-MCI patients displayed widespread deterioration in microvascular cerebral perfusion associated with capillary dysfunction. No such changes were observed in the other two groups, suggesting that the dysfunction in capillary perfusion is linked to the AD pathophysiology. The observed capillary dysfunction may limit local oxygenation in AD leading to downstream β-amyloid aggregation, tau hyperphosphorylation, neuroinflammation and neuronal dysfunction. The findings are in agreement with the capillary dysfunction hypothesis of AD, suggesting that increasing heterogeneity of capillary blood flow is a primary pathological event in AD.

KW - Alzheimer's disease

KW - Capillary dysfunction

KW - Magnetic resonance imaging

KW - Mild cognitive impairment

KW - Perfusion

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U2 - 10.1016/j.nbas.2022.100035

DO - 10.1016/j.nbas.2022.100035

M3 - Journal article

C2 - 36908896

SN - 2589-9589

VL - 2

JO - Aging Brain

JF - Aging Brain

M1 - 100035

ER -

Capillary function progressively deteriorates in prodromal Alzheimer’s disease: A longitudinal MRI perfusion study

Abstract

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