Global Burden of Small Vessel Disease–Related Brain Changes on MRI Predicts Cognitive and Functional Decline

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Supplemental Digital Content is available in the text.

Background and Purpose—

Cerebral small vessel disease is characterized by a wide range of focal and global brain changes. We used a magnetic resonance imaging segmentation tool to quantify multiple types of small vessel disease–related brain changes and examined their individual and combined predictive value on cognitive and functional abilities.

Methods—

Magnetic resonance imaging scans of 560 older individuals from LADIS (Leukoaraiosis and Disability Study) were analyzed using automated atlas- and convolutional neural network–based segmentation methods yielding volumetric measures of white matter hyperintensities, lacunes, enlarged perivascular spaces, chronic cortical infarcts, and global and regional brain atrophy. The subjects were followed up with annual neuropsychological examinations for 3 years and evaluation of instrumental activities of daily living for 7 years.

Results—

The strongest predictors of cognitive performance and functional outcome over time were the total volumes of white matter hyperintensities, gray matter, and hippocampi ( P<0.001 for global cognitive function, processing speed, executive functions, and memory and P<0.001 for poor functional outcome). Volumes of lacunes, enlarged perivascular spaces, and cortical infarcts were significantly associated with part of the outcome measures, but their contribution was weaker. In a multivariable linear mixed model, volumes of white matter hyperintensities, lacunes, gray matter, and hippocampi remained as independent predictors of cognitive impairment. A combined measure of these markers based on Z scores strongly predicted cognitive and functional outcomes ( P<0.001) even above the contribution of the individual brain changes.

Conclusions—

Global burden of small vessel disease–related brain changes as quantified by an image segmentation tool is a powerful predictor of long-term cognitive decline and functional disability. A combined measure of white matter hyperintensities, lacunar, gray matter, and hippocampal volumes could be used as an imaging marker associated with vascular cognitive impairment.

Related collections

Most cited references 18

Record: found
Abstract: found
Article: found

Is Open Access

Update on cerebral small vessel disease: a dynamic whole-brain disease

Yulu Shi, Joanna M. Wardlaw (2016)

Cerebral small vessel disease (CSVD) is a very common neurological disease in older people. It causes stroke and dementia, mood disturbance and gait problems. Since it is difficult to visualise CSVD pathologies in vivo, the diagnosis of CSVD has relied on imaging findings including white matter hyperintensities, lacunar ischaemic stroke, lacunes, microbleeds, visible perivascular spaces and many haemorrhagic strokes. However, variations in the use of definition and terms of these features have probably caused confusion and difficulties in interpreting results of previous studies. A standardised use of terms should be encouraged in CSVD research. These CSVD features have long been regarded as different lesions, but emerging evidence has indicated that they might share some common intrinsic microvascular pathologies and therefore, owing to its diffuse nature, CSVD should be regarded as a ‘whole-brain disease’. Single antiplatelet (for acute lacunar ischaemic stroke) and management of traditional risk factors still remain the most important therapeutic and preventive approach, due to limited understanding of pathophysiology in CSVD. Increasing evidence suggests that new studies should consider drugs that target endothelium and blood–brain barrier to prevent and treat CSVD. Epidemiology of CSVD might differ in Asian compared with Western populations (where most results and guidelines about CSVD and stroke originate), but more community-based data and clear stratification of stroke types are required to address this.

0 comments Cited 180 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Impact of Age-Related Cerebral White Matter Changes on the Transition to Disability – The LADIS Study: Rationale, Design and Methodology

Leonardo Pantoni, Anna Maria Basile, Giovanni Pracucci … (2004)

Age-related white matter changes (ARWMC) on brain MRI have been associated with cognitive, motor, mood and urinary disturbances. These factors are known to contribute to disability in elderly people, but the impact of ARWMC and of their progression on the transition to disability is not determined. The LADIS (Leukoaraiosis and Disability in the Elderly) study aims at assessing the role of ARWMC as an independent predictor of the transition to disability in initially nondisabled elderly (65–84 years). Subjects who are not impaired or impaired on only 1 item of the Instrumental Activity of Daily Living (IADL) scale, presenting with different grades of ARWMC severity, were enrolled. Eleven European centers are involved. All the patients were assessed at baseline using an extensive set of clinical and functional tests including global functioning, cognitive, motor, psychiatric and quality of life measures. MRI studies were performed at baseline and will be repeated at the end of the follow-up period to evaluate changes of ARWMC and other lesions. ARWMC were categorized into mild, moderate or severe using the scale of Fazekas et al. For each ARWMC severity class, the primary study outcome is the transition to disability defined as an impairment on 2 or more IADL scale items. Secondary outcomes are the occurrence of dementia, depression, vascular events or death. Six-hundred and thirty-nine subjects (mean age 74.13 ± 5.0 years, M/F: 288/351) were enrolled in a hospital-based setting and are being followed up for up to 3 years. The large and comprehensive set of measures in LADIS enables a comprehensive description of their functional and clinical features to be examined in relation to different morphological patterns and severity of ARWMC. The longitudinal design will give insight into the possible role of ARWMC and their progression as an independent contributor to disability in the elderly, eventually helping to develop preventive strategies to reduce the burden of disability in late life. The study results may also help to standardize, on an international basis, tools and criteria to identify early stages of disability.

0 comments Cited 123 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Impact of white matter hyperintensities scoring method on correlations with clinical data: the LADIS study.

Gunhild Waldemar, Timo Erkinjuntti, Philip Scheltens … (2006)

White matter hyperintensities (WMH) are associated with decline in cognition, gait, mood, and urinary continence. Associations may depend on the method used for measuring WMH. We investigated the ability of different WMH scoring methods to detect differences in WMH load between groups with and without symptoms. We used data of 618 independently living elderly with WMH collected in the Leukoaraiosis And DISability (LADIS) study. Subjects with and without symptoms of depression, gait disturbances, urinary incontinence, and memory decline were compared with respect to WMH load measured qualitatively using 3 widely used visual rating scales (Fazekas, Scheltens, and Age-Related White Matter Changes scales) and quantitatively with a semiautomated volumetric technique and an automatic lesion count. Statistical significance between groups was assessed with the chi2 and Mann-Whitney tests. In addition, the punctate and confluent lesion type with comparable WMH volume were compared with respect to the clinical data using Student t test and chi2 test. Direct comparison of visual ratings with volumetry was done using curve fitting. Visual and volumetric assessment detected differences in WMH between groups with respect to gait disturbances and age. WMH volume measurement was more sensitive than visual scores with respect to memory symptoms. Number of lesions nor lesion type correlated with any of the clinical data. For all rating scales, a clear but nonlinear relationship was established with WMH volume. Visual rating scales display ceiling effects and poor discrimination of absolute lesion volumes. Consequently, they may be less sensitive in differentiating clinical groups.

0 comments Cited 93 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Stroke

Journal ID (iso-abbrev): Stroke

Journal ID (publisher-id): STR

Title: Stroke

Publisher: Lippincott Williams & Wilkins

ISSN (Print): 0039-2499

ISSN (Electronic): 1524-4628

Publication date (Print): January 2020

Publication date (Electronic): 08 November 2019

Volume: 51

Issue: 1

Pages: 170-178

Affiliations

[1 ]From the Clinical Neurosciences, Neurology, University of Helsinki and Helsinki University Hospital (H.J., H.M.L., S. Melkas, T.E.), Finland

[2 ]Department of Psychology and Logopedics, Faculty of Medicine (H.J., H.M.L.), Finland

[3 ]Medical Imaging Center, Radiology, University of Helsinki and Helsinki University Hospital (A.K.), Finland

[4 ]Combinostics, Ltd, Finland (J.K., T.N., J.L.)

[5 ]VTT Technical Research Centre of Finland (J.K., J.L.)

[6 ]Faculty of Health Sciences, University of Eastern Finland (J.K.)

[7 ]Department of Radiology, Medical Imaging Center, Tampere University Hospital, Finland (A.B.)

[8 ]Biomedical Image Analysis Group, Department of Computing, Imperial College London, United Kingdom (D.R.)

[9 ]Department of Radiology and Nuclear Medicine (F.B.), Neuroscience Campus Amsterdam, VU University Medical Center, the Netherlands

[10 ]Alzheimer Center and Department of Neurology (P.S.), Neuroscience Campus Amsterdam, VU University Medical Center, the Netherlands

[11 ]Institutes of Neurology and Healthcare Engineering, University College London, United Kingdom (F.B.)

[12 ]NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust, University College London, United Kingdom (F.B.)

[13 ]Department of Neurology, Medical University of Graz, Austria (R.S., F.F.)

[14 ]Department of Neurosciences, Santa Maria Hospital, University of Lisbon, Portugal (S. Madureira, A.V.)

[15 ]Sahlgrenska Academy, Institute of Neuroscience and Physiology, Section for Psychiatry and Neurochemistry, University of Gothenburg, Sweden (A.W.)

[16 ]Department of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Karolinska Institutet, Sweden (L.-O.W.)

[17 ]Department of Neurology, Danish Dementia Research Centre, Rigshospitalet, University of Copenhagen, Denmark (G.W.)

[18 ]Department of Neurology, Hopital Lariboisiere, APHP and INSERM U1161–University Denis Diderot (DHU NeuroVasc), France (H.C.)

[19 ]Medical Faculty Mannheim, University of Heidelberg, Germany (M.H.)

[20 ]Department of Psychiatry, University of Cambridge, United Kingdom (J.O.)

[21 ]Institute of Neuroscience, Italian National Research Council (D.I.)

[22 ]Department NEUROFARBA, University of Florence, Italy (D.I.)

[23 ]Department of Neuroscience and Biomedical Engineering, School of Science, Aalto University, Finland (J.L.)

[24 ]L. Sacco Department of Biomedical and Clinical Sciences, University of Milan, Italy (L.P.).

Author notes

Correspondence to Hanna Jokinen, PhD, Neurocenter, Helsinki University Hospital, PO Box 302, 00029 HUS, Finland. Email hanna.jokinen@ 123456helsinki.fi

Article

Accession ID: 00028

DOI: 10.1161/STROKEAHA.119.026170

PMC ID: 6924941

PubMed ID: 31699021

SO-VID: 29ddbf33-0476-49c4-bca0-d86f7bb053b6

License:

Stroke is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.

History

Date received : 30 April 2019

Date revision received : 29 September 2019

Date accepted : 4 October 2019

Custom metadata

OPEN-ACCESS TRUE

Keywords: brain,cerebral small vessel diseases,humans,image processing, computer assisted,neuropsychology

Data availability:

Keywords: brain, cerebral small vessel diseases, humans, image processing, computer assisted, neuropsychology

Global Burden of Small Vessel Disease–Related Brain Changes on MRI Predicts Cognitive and Functional Decline

Read this article at

Abstract

Background and Purpose—

Methods—

Results—

Conclusions—

Related collections

UCL: UN SDG 03 Good Health and Well-Being

Most cited references 18

Update on cerebral small vessel disease: a dynamic whole-brain disease

Impact of Age-Related Cerebral White Matter Changes on the Transition to Disability – The LADIS Study: Rationale, Design and Methodology

Impact of white matter hyperintensities scoring method on correlations with clinical data: the LADIS study.

Author and article information

Journal

Affiliations

Author notes

Article

History

Categories

Custom metadata

Comments

Comment on this article

Cited by 69

Most referenced authors 522