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

Research output: Contribution to journalArticle


  • 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'Brien
  • Domenico Inzitari
  • Leonardo Pantoni
  • Timo Erkinjuntti

Research units

  • University of Helsinki
  • Combinostics, Ltd
  • VTT Technical Research Centre of Finland
  • University of Eastern Finland
  • Tampere University Hospital
  • Imperial College London
  • Vrije Universiteit Amsterdam
  • University College London
  • Medical University of Graz
  • Hospital District of Helsinki and Uusimaa
  • University of Gothenburg
  • Karolinska Institutet
  • University of Copenhagen
  • Université Paris 7
  • Institut für Theoretische Astrophysik
  • University of Cambridge
  • CNR-ENEA-EURATOM Association
  • University of Florence
  • Ospedale Luigi Sacco


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
Issue number1
Publication statusPublished - 1 Jan 2020
MoE publication typeA1 Journal article-refereed

    Research areas

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

ID: 40337805