SORA

Advancing, promoting and sharing knowledge of health through excellence in teaching, clinical practice and research into the prevention and treatment of illness

Neuropathology of White Matter Lesions, Blood-Brain Barrier Dysfunction, and Dementia.

Hainsworth, AH; Minett, T; Andoh, J; Forster, G; Bhide, I; Barrick, TR; Elderfield, K; Jeevahan, J; Markus, HS; Bridges, LR (2017) Neuropathology of White Matter Lesions, Blood-Brain Barrier Dysfunction, and Dementia. Stroke, 48 (10). pp. 2799-2804. ISSN 1524-4628 https://doi.org/10.1161/STROKEAHA.117.018101
SGUL Authors: Barrick, Thomas Richard Hainsworth, Atticus Henry

[img] Microsoft Word (.docx) Accepted Version
Available under License ["licenses_description_publisher" not defined].

Download (133kB)

Abstract

BACKGROUND AND PURPOSE: We tested whether blood-brain barrier dysfunction in subcortical white matter is associated with white matter abnormalities or risk of clinical dementia in older people (n=126; mean age 86.4, SD: 7.7 years) in the MRC CFAS (Medical Research Council Cognitive Function and Ageing Study). METHODS: Using digital pathology, we quantified blood-brain barrier dysfunction (defined by immunohistochemical labeling for the plasma marker fibrinogen). This was assessed within subcortical white matter tissue samples harvested from postmortem T2 magnetic resonance imaging (MRI)-detected white matter hyperintensities, from normal-appearing white matter (distant from coexistent MRI-defined hyperintensities), and from equivalent areas in MRI normal brains. Histopathologic lesions were defined using a marker for phagocytic microglia (CD68, clone PGM1). RESULTS: Extent of fibrinogen labeling was not significantly associated with white matter abnormalities defined either by MRI (odds ratio, 0.90; 95% confidence interval, 0.79-1.03; P=0.130) or by histopathology (odds ratio, 0.93; 95% confidence interval, 0.77-1.12; P=0.452). Among participants with normal MRI (no detectable white matter hyperintensities), increased fibrinogen was significantly related to decreased risk of clinical dementia (odds ratio, 0.74; 95% confidence interval, 0.58-0.94; P=0.013). Among participants with histological lesions, increased fibrinogen was related to increased risk of dementia (odds ratio, 2.26; 95% confidence interval, 1.25-4.08; P=0.007). CONCLUSIONS: Our data suggest that some degree of blood-brain barrier dysfunction is common in older people and that this may be related to clinical dementia risk, additional to standard MRI biomarkers.

Item Type: Article
Additional Information: This is a non-final version of an article published in final form in Hainsworth, AH; Minett, T; Andoh, J; Forster, G; Bhide, I; Barrick, TR; Elderfield, K; Jeevahan, J; Markus, HS; Bridges, LR (2017) Neuropathology of White Matter Lesions, Blood-Brain Barrier Dysfunction, and Dementia. Stroke. 2017;48:2799-2804
Keywords: dementia, fibrinogen, leukoaraiosis, neuropathology, vascular cognitive impairment, white matter, dementia, fibrinogen, leukoaraiosis, neuropathology, vascular cognitive impairment, white matter, Neurology & Neurosurgery, 1103 Clinical Sciences, 1102 Cardiovascular Medicine And Haematology, 1109 Neurosciences
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Neuroscience (INCCNS)
Journal or Publication Title: Stroke
ISSN: 1524-4628
Language: eng
Dates:
DateEvent
October 2017Published
30 August 2017Published Online
1 August 2017Accepted
Publisher License: Publisher's own licence
Projects:
Project IDFunderFunder ID
G9901400Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
G0601022Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
PG146/151Alzheimer's Societyhttp://dx.doi.org/10.13039/501100000320
20140901Alzheimer Drug Discovery Foundationhttp://dx.doi.org/10.13039/100002565
PPG2014A-8Alzheimer's Research UKUNSPECIFIED
PubMed ID: 28855392
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/109138
Publisher's version: https://doi.org/10.1161/STROKEAHA.117.018101

Actions (login required)

Edit Item Edit Item