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

Hanna Jokinen, Juha Koikkalainen, Hanna M. Laakso, Susanna Melkas, Tuomas Nieminen, Antti Brander, Antti Korvenoja, Daniel Rueckert, Frederik Barkhof, Philip Scheltens, Reinhold Schmidt, Franz Fazekas, Sofia Madureira, Ana Verdelho, Anders Wallin, Lars Olof Wahlund, Gunhild Waldemar, Hugues Chabriat, Michael Hennerici, John O'BrienDomenico Inzitari, Jyrki Lötjönen, Leonardo Pantoni, Timo Erkinjuntti

Research output: Contribution to journalArticleScientificpeer-review

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)170-178
Number of pages9
JournalStroke
Volume51
Issue number1
Early online date8 Nov 2019
DOIs
Publication statusPublished - 1 Jan 2020
MoE publication typeA1 Journal article-refereed

Fingerprint

Brain Diseases
Hippocampus
Brain
Cerebral Small Vessel Diseases
Leukoaraiosis
Magnetic Resonance Imaging
Aptitude
Atlases
Executive Function
Activities of Daily Living
Cognition
Atrophy
Blood Vessels
Linear Models
Outcome Assessment (Health Care)
Cognitive Dysfunction
White Matter
Gray Matter

Keywords

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

Cite this

Jokinen, H., Koikkalainen, J., Laakso, H. M., Melkas, S., Nieminen, T., Brander, A., ... Erkinjuntti, T. (2020). Global Burden of Small Vessel Disease-Related Brain Changes on MRI Predicts Cognitive and Functional Decline. Stroke, 51(1), 170-178. https://doi.org/10.1161/STROKEAHA.119.026170
Jokinen, Hanna ; Koikkalainen, Juha ; Laakso, Hanna M. ; Melkas, Susanna ; Nieminen, Tuomas ; Brander, Antti ; Korvenoja, Antti ; Rueckert, Daniel ; Barkhof, Frederik ; Scheltens, Philip ; Schmidt, Reinhold ; Fazekas, Franz ; Madureira, Sofia ; Verdelho, Ana ; Wallin, Anders ; Wahlund, Lars Olof ; Waldemar, Gunhild ; Chabriat, Hugues ; Hennerici, Michael ; O'Brien, John ; Inzitari, Domenico ; Lötjönen, Jyrki ; Pantoni, Leonardo ; Erkinjuntti, Timo. / Global Burden of Small Vessel Disease-Related Brain Changes on MRI Predicts Cognitive and Functional Decline. In: Stroke. 2020 ; Vol. 51, No. 1. pp. 170-178.
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abstract = "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.",
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author = "Hanna Jokinen and Juha Koikkalainen and Laakso, {Hanna M.} and Susanna Melkas and Tuomas Nieminen and Antti Brander and Antti Korvenoja and Daniel Rueckert and Frederik Barkhof and Philip Scheltens and Reinhold Schmidt and Franz Fazekas and Sofia Madureira and Ana Verdelho and Anders Wallin and Wahlund, {Lars Olof} and Gunhild Waldemar and Hugues Chabriat and Michael Hennerici and John O'Brien and Domenico Inzitari and Jyrki L{\"o}tj{\"o}nen and Leonardo Pantoni and Timo Erkinjuntti",
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Jokinen, H, Koikkalainen, J, Laakso, HM, Melkas, S, Nieminen, T, Brander, A, Korvenoja, A, Rueckert, D, Barkhof, F, Scheltens, P, Schmidt, R, Fazekas, F, Madureira, S, Verdelho, A, Wallin, A, Wahlund, LO, Waldemar, G, Chabriat, H, Hennerici, M, O'Brien, J, Inzitari, D, Lötjönen, J, Pantoni, L & Erkinjuntti, T 2020, 'Global Burden of Small Vessel Disease-Related Brain Changes on MRI Predicts Cognitive and Functional Decline', Stroke, vol. 51, no. 1, pp. 170-178. https://doi.org/10.1161/STROKEAHA.119.026170

Global Burden of Small Vessel Disease-Related Brain Changes on MRI Predicts Cognitive and Functional Decline. / Jokinen, Hanna; Koikkalainen, Juha; Laakso, Hanna M.; Melkas, Susanna; Nieminen, Tuomas; Brander, Antti; Korvenoja, Antti; Rueckert, Daniel; Barkhof, Frederik; Scheltens, Philip; Schmidt, Reinhold; Fazekas, Franz; Madureira, Sofia; Verdelho, Ana; Wallin, Anders; Wahlund, Lars Olof; Waldemar, Gunhild; Chabriat, Hugues; Hennerici, Michael; O'Brien, John; Inzitari, Domenico; Lötjönen, Jyrki; Pantoni, Leonardo; Erkinjuntti, Timo.

In: Stroke, Vol. 51, No. 1, 01.01.2020, p. 170-178.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Global Burden of Small Vessel Disease-Related Brain Changes on MRI Predicts Cognitive and Functional Decline

AU - Jokinen, Hanna

AU - Koikkalainen, Juha

AU - Laakso, Hanna M.

AU - Melkas, Susanna

AU - Nieminen, Tuomas

AU - Brander, Antti

AU - Korvenoja, Antti

AU - Rueckert, Daniel

AU - Barkhof, Frederik

AU - Scheltens, Philip

AU - Schmidt, Reinhold

AU - Fazekas, Franz

AU - Madureira, Sofia

AU - Verdelho, Ana

AU - Wallin, Anders

AU - Wahlund, Lars Olof

AU - Waldemar, Gunhild

AU - Chabriat, Hugues

AU - Hennerici, Michael

AU - O'Brien, John

AU - Inzitari, Domenico

AU - Lötjönen, Jyrki

AU - Pantoni, Leonardo

AU - Erkinjuntti, Timo

PY - 2020/1/1

Y1 - 2020/1/1

N2 - 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.

AB - 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.

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KW - cerebral small vessel diseases

KW - humans

KW - image processing, computer assisted

KW - neuropsychology

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U2 - 10.1161/STROKEAHA.119.026170

DO - 10.1161/STROKEAHA.119.026170

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Jokinen H, Koikkalainen J, Laakso HM, Melkas S, Nieminen T, Brander A et al. Global Burden of Small Vessel Disease-Related Brain Changes on MRI Predicts Cognitive and Functional Decline. Stroke. 2020 Jan 1;51(1):170-178. https://doi.org/10.1161/STROKEAHA.119.026170