Blood-brain barrier failure as a core mechanism in cerebral small vessel disease and dementia: evidence from a cohort study

Joanna M. Wardlaw; Stephen J. Makin; Maria C. Valdés Hernández; Paul A. Armitage; Anna K. Heye; Francesca M. Chappell; Susana Muñoz-Maniega; Eleni Sakka; Kirsten Shuler; Martin S. Dennis; Michael J. Thrippleton

doi:10.1016/j.jalz.2016.09.006

Blood-brain barrier failure as a core mechanism in cerebral small vessel disease and dementia: evidence from a cohort study

Joanna M. Wardlaw^* (Corresponding Author), Stephen J. Makin, Maria C. Valdés Hernández, Paul A. Armitage, Anna K. Heye, Francesca M. Chappell, Susana Muñoz-Maniega, Eleni Sakka, Kirsten Shuler, Martin S. Dennis, Michael J. Thrippleton

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

171 Citations (Scopus)

7 Downloads (Pure)

Abstract

IntroductionSmall vessel disease (SVD) is a common contributor to dementia. Subtle blood-brain barrier (BBB) leakage may be important in SVD-induced brain damage.MethodsWe assessed imaging, clinical variables, and cognition in patients with mild (i.e., nondisabling) ischemic lacunar or cortical stroke. We analyzed BBB leakage, interstitial fluid, and white matter integrity using multimodal tissue-specific spatial analysis around white matter hyperintensities (WMH). We assessed predictors of 1 year cognition, recurrent stroke, and dependency.ResultsIn 201 patients, median age 67 (range 34–97), BBB leakage, and interstitial fluid were higher in WMH than normal-appearing white matter; leakage in normal-appearing white matter increased with proximity to WMH (P < .0001), with WMH severity (P = .033), age (P = .03), and hypertension (P < .0001). BBB leakage in WMH predicted declining cognition at 1 year.DiscussionBBB leakage increases in normal-appearing white matter with WMH and predicts worsening cognition. Interventions to reduce BBB leakage may prevent SVD-associated dementia.

Original language	English
Pages (from-to)	634-643
Number of pages	10
Journal	Alzheimer's and Dementia
Volume	13
Issue number	6
Early online date	27 Oct 2016
DOIs	https://doi.org/10.1016/j.jalz.2016.09.006
Publication status	Published - 1 Jun 2017

Bibliographical note

We thank the participants, their relatives, and carers for their time and patience in contributing to the study, the staff of NHS Lothian Stroke Services, and the Brain Research Imaging Centre Edinburgh for their assistance in recruiting and assessing the patients. Funding: Wellcome Trust (WT088134/Z/09/A), Row Fogo Charitable Trust, Scottish Funding Council Scottish Imaging Network A Platform for Scientific Excellence collaboration, Age-UK Disconnected Mind Study, NHS Lothian R+D Department, and The Brain Research Imaging Centre Edinburgh (http://www.sbirc.ed.ac.uk/). Conflict of interest: All authors report grants from Wellcome Trust, grants from Row Fogo Charitable Trust, grants from Age UK, and grants from Scottish Funding Council, during the conduct of the study. Role of the funding source: The funders had no role in the planning, execution, analysis of the study, or preparation of the manuscript or decision to submit. The authors hold the data.

Keywords

blood brain barrier
small vessel disease
stroke
white matter hyperintensities
dementia

Access to Document

10.1016/j.jalz.2016.09.006Licence: CC BY

Wardlaw_etal_AD_Blood_Brain_VOR
This is anopen access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Final published version, 1.59 MBLicence: CC BY

Stephen Makin
- School of Medicine, Medical Sciences & Nutrition, Applied Health Sciences - Senior Lecturer (Clinical)
Person: Clinical Academic

Cite this

Wardlaw, J. M., Makin, S. J., Valdés Hernández, M. C., Armitage, P. A., Heye, A. K., Chappell, F. M., Muñoz-Maniega, S., Sakka, E., Shuler, K., Dennis, M. S., & Thrippleton, M. J. (2017). Blood-brain barrier failure as a core mechanism in cerebral small vessel disease and dementia: evidence from a cohort study. Alzheimer's and Dementia, 13(6), 634-643. https://doi.org/10.1016/j.jalz.2016.09.006

Wardlaw, JM, Makin, SJ, Valdés Hernández, MC, Armitage, PA, Heye, AK, Chappell, FM, Muñoz-Maniega, S, Sakka, E, Shuler, K, Dennis, MS & Thrippleton, MJ 2017, 'Blood-brain barrier failure as a core mechanism in cerebral small vessel disease and dementia: evidence from a cohort study', Alzheimer's and Dementia, vol. 13, no. 6, pp. 634-643. https://doi.org/10.1016/j.jalz.2016.09.006

@article{7696d48e56ce424a9048743dceae0eed,

title = "Blood-brain barrier failure as a core mechanism in cerebral small vessel disease and dementia: evidence from a cohort study",

abstract = "IntroductionSmall vessel disease (SVD) is a common contributor to dementia. Subtle blood-brain barrier (BBB) leakage may be important in SVD-induced brain damage.MethodsWe assessed imaging, clinical variables, and cognition in patients with mild (i.e., nondisabling) ischemic lacunar or cortical stroke. We analyzed BBB leakage, interstitial fluid, and white matter integrity using multimodal tissue-specific spatial analysis around white matter hyperintensities (WMH). We assessed predictors of 1 year cognition, recurrent stroke, and dependency.ResultsIn 201 patients, median age 67 (range 34–97), BBB leakage, and interstitial fluid were higher in WMH than normal-appearing white matter; leakage in normal-appearing white matter increased with proximity to WMH (P < .0001), with WMH severity (P = .033), age (P = .03), and hypertension (P < .0001). BBB leakage in WMH predicted declining cognition at 1 year.DiscussionBBB leakage increases in normal-appearing white matter with WMH and predicts worsening cognition. Interventions to reduce BBB leakage may prevent SVD-associated dementia.",

keywords = "blood brain barrier, small vessel disease, stroke, white matter hyperintensities, dementia",

author = "Wardlaw, {Joanna M.} and Makin, {Stephen J.} and {Vald{\'e}s Hern{\'a}ndez}, {Maria C.} and Armitage, {Paul A.} and Heye, {Anna K.} and Chappell, {Francesca M.} and Susana Mu{\~n}oz-Maniega and Eleni Sakka and Kirsten Shuler and Dennis, {Martin S.} and Thrippleton, {Michael J.}",

note = "We thank the participants, their relatives, and carers for their time and patience in contributing to the study, the staff of NHS Lothian Stroke Services, and the Brain Research Imaging Centre Edinburgh for their assistance in recruiting and assessing the patients. Funding: Wellcome Trust (WT088134/Z/09/A), Row Fogo Charitable Trust, Scottish Funding Council Scottish Imaging Network A Platform for Scientific Excellence collaboration, Age-UK Disconnected Mind Study, NHS Lothian R+D Department, and The Brain Research Imaging Centre Edinburgh (http://www.sbirc.ed.ac.uk/). Conflict of interest: All authors report grants from Wellcome Trust, grants from Row Fogo Charitable Trust, grants from Age UK, and grants from Scottish Funding Council, during the conduct of the study. Role of the funding source: The funders had no role in the planning, execution, analysis of the study, or preparation of the manuscript or decision to submit. The authors hold the data. ",

year = "2017",

month = jun,

day = "1",

doi = "10.1016/j.jalz.2016.09.006",

language = "English",

volume = "13",

pages = "634--643",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

publisher = "Elsevier Inc.",

number = "6",

}

TY - JOUR

T1 - Blood-brain barrier failure as a core mechanism in cerebral small vessel disease and dementia

T2 - evidence from a cohort study

AU - Wardlaw, Joanna M.

AU - Makin, Stephen J.

AU - Valdés Hernández, Maria C.

AU - Armitage, Paul A.

AU - Heye, Anna K.

AU - Chappell, Francesca M.

AU - Muñoz-Maniega, Susana

AU - Sakka, Eleni

AU - Shuler, Kirsten

AU - Dennis, Martin S.

AU - Thrippleton, Michael J.

N1 - We thank the participants, their relatives, and carers for their time and patience in contributing to the study, the staff of NHS Lothian Stroke Services, and the Brain Research Imaging Centre Edinburgh for their assistance in recruiting and assessing the patients. Funding: Wellcome Trust (WT088134/Z/09/A), Row Fogo Charitable Trust, Scottish Funding Council Scottish Imaging Network A Platform for Scientific Excellence collaboration, Age-UK Disconnected Mind Study, NHS Lothian R+D Department, and The Brain Research Imaging Centre Edinburgh (http://www.sbirc.ed.ac.uk/). Conflict of interest: All authors report grants from Wellcome Trust, grants from Row Fogo Charitable Trust, grants from Age UK, and grants from Scottish Funding Council, during the conduct of the study. Role of the funding source: The funders had no role in the planning, execution, analysis of the study, or preparation of the manuscript or decision to submit. The authors hold the data.

PY - 2017/6/1

Y1 - 2017/6/1

N2 - IntroductionSmall vessel disease (SVD) is a common contributor to dementia. Subtle blood-brain barrier (BBB) leakage may be important in SVD-induced brain damage.MethodsWe assessed imaging, clinical variables, and cognition in patients with mild (i.e., nondisabling) ischemic lacunar or cortical stroke. We analyzed BBB leakage, interstitial fluid, and white matter integrity using multimodal tissue-specific spatial analysis around white matter hyperintensities (WMH). We assessed predictors of 1 year cognition, recurrent stroke, and dependency.ResultsIn 201 patients, median age 67 (range 34–97), BBB leakage, and interstitial fluid were higher in WMH than normal-appearing white matter; leakage in normal-appearing white matter increased with proximity to WMH (P < .0001), with WMH severity (P = .033), age (P = .03), and hypertension (P < .0001). BBB leakage in WMH predicted declining cognition at 1 year.DiscussionBBB leakage increases in normal-appearing white matter with WMH and predicts worsening cognition. Interventions to reduce BBB leakage may prevent SVD-associated dementia.

AB - IntroductionSmall vessel disease (SVD) is a common contributor to dementia. Subtle blood-brain barrier (BBB) leakage may be important in SVD-induced brain damage.MethodsWe assessed imaging, clinical variables, and cognition in patients with mild (i.e., nondisabling) ischemic lacunar or cortical stroke. We analyzed BBB leakage, interstitial fluid, and white matter integrity using multimodal tissue-specific spatial analysis around white matter hyperintensities (WMH). We assessed predictors of 1 year cognition, recurrent stroke, and dependency.ResultsIn 201 patients, median age 67 (range 34–97), BBB leakage, and interstitial fluid were higher in WMH than normal-appearing white matter; leakage in normal-appearing white matter increased with proximity to WMH (P < .0001), with WMH severity (P = .033), age (P = .03), and hypertension (P < .0001). BBB leakage in WMH predicted declining cognition at 1 year.DiscussionBBB leakage increases in normal-appearing white matter with WMH and predicts worsening cognition. Interventions to reduce BBB leakage may prevent SVD-associated dementia.

KW - blood brain barrier

KW - small vessel disease

KW - stroke

KW - white matter hyperintensities

KW - dementia

U2 - 10.1016/j.jalz.2016.09.006

DO - 10.1016/j.jalz.2016.09.006

M3 - Article

SN - 1552-5260

VL - 13

SP - 634

EP - 643

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 6

ER -

Blood-brain barrier failure as a core mechanism in cerebral small vessel disease and dementia: evidence from a cohort study

Abstract

Bibliographical note

Keywords

Access to Document

Fingerprint

Profiles

Stephen Makin

Cite this