SORA

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

Longitudinal patterns of leukoaraiosis and brain atrophy in symptomatic small vessel disease.

Lambert, C; Benjamin, P; Zeestraten, E; Lawrence, AJ; Barrick, TR; Markus, HS (2016) Longitudinal patterns of leukoaraiosis and brain atrophy in symptomatic small vessel disease. Brain, 139 (4). pp. 1136-1151. ISSN 1460-2156 https://doi.org/10.1093/brain/aww009
SGUL Authors: Lawrence, Andrew John Lambert, Christian Paul Benjamin, Philip

[img]
Preview
PDF Published Version
Available under License Creative Commons Attribution.

Download (1MB) | Preview

Abstract

Cerebral small vessel disease is a common condition associated with lacunar stroke, cognitive impairment and significant functional morbidity. White matter hyperintensities and brain atrophy, seen on magnetic resonance imaging, are correlated with increasing disease severity. However, how the two are related remains an open question. To better define the relationship between white matter hyperintensity growth and brain atrophy, we applied a semi-automated magnetic resonance imaging segmentation analysis pipeline to a 3-year longitudinal cohort of 99 subjects with symptomatic small vessel disease, who were followed-up for ≥1 years. Using a novel two-stage warping pipeline with tissue repair step, voxel-by-voxel rate of change maps were calculated for each tissue class (grey matter, white matter, white matter hyperintensities and lacunes) for each individual. These maps capture both the distribution of disease and spatial information showing local rates of growth and atrophy. These were analysed to answer three primary questions: first, is there a relationship between whole brain atrophy and magnetic resonance imaging markers of small vessel disease (white matter hyperintensities or lacune volume)? Second, is there regional variation within the cerebral white matter in the rate of white matter hyperintensity progression? Finally, are there regionally specific relationships between the rates of white matter hyperintensity progression and cortical grey matter atrophy? We demonstrate that the rates of white matter hyperintensity expansion and grey matter atrophy are strongly correlated (Pearson's R = -0.69, P < 1 × 10(-7)), and significant grey matter loss and whole brain atrophy occurs annually (P < 0.05). Additionally, the rate of white matter hyperintensity growth was heterogeneous, occurring more rapidly within long association fasciculi. Using voxel-based quantification (family-wise error corrected P < 0.05), we show the rate of white matter hyperintensity progression is associated with increases in cortical grey matter atrophy rates, in the medial-frontal, orbito-frontal, parietal and occipital regions. Conversely, increased rates of global grey matter atrophy are significantly associated with faster white matter hyperintensity growth in the frontal and parietal regions. Together, these results link the progression of white matter hyperintensities with increasing rates of regional grey matter atrophy, and demonstrate that grey matter atrophy is the major contributor to whole brain atrophy in symptomatic cerebral small vessel disease. These measures provide novel insights into the longitudinal pathogenesis of small vessel disease, and imply that therapies aimed at reducing progression of white matter hyperintensities via end-arteriole damage may protect against secondary brain atrophy and consequent functional morbidity.

Item Type: Article
Additional Information: © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: atrophy, longitudinal, small vessel disease, voxel-based quantification, white matter hyperintensities, Neurology & Neurosurgery, 11 Medical And Health Sciences, 17 Psychology And Cognitive Sciences
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: Brain
ISSN: 1460-2156
Language: ENG
Dates:
DateEvent
1 March 2016Published
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
081589Wellcome Trusthttp://dx.doi.org/10.13039/100004440
ARUK-PG2013-2Arthritis Research UKhttp://dx.doi.org/10.13039/501100000341
PubMed ID: 26936939
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/107771
Publisher's version: https://doi.org/10.1093/brain/aww009

Actions (login required)

Edit Item Edit Item