Cerebral white matter hyperintensity volumes: Normative age- and sex-specific values from 15 population-based cohorts comprising 14,876 individuals

Floor A S de Kort; Elisabeth J Vinke; Ewoud J van der Lelij; Devasuda Anblagan; Mark E Bastin; Alexa Beiser; Henry Brodaty; Nishi Chaturvedi; Bastian Cheng; Simon R Cox; Charles DeCarli; Christian Enzinger; Evan Fletcher; Richard Frayne; Marius de Groot; Felicia Huang; M Arfan Ikram; Jiyang Jiang; Bonnie Y K Lam; Pauline Maillard; Carola Mayer; Cheryl R McCreary; Vincent Mok; Susana Muñoz Maniega; Marvin Petersen; Genady Roshchupkin; Perminder S Sachdev; Reinhold Schmidt; Stephan Seiler; Sudha Seshadri; Carole H Sudre; Götz Thomalla; Raphael Twerenbold; Maria Valdés Hernández; Meike W Vernooij; Joanna M Wardlaw; Wei Wen; Hugo J Kuijf; Geert Jan Biessels; J Matthijs Biesbroek

doi:10.1016/j.neurobiolaging.2024.11.006

Cerebral white matter hyperintensity volumes: Normative age- and sex-specific values from 15 population-based cohorts comprising 14,876 individuals

Neurobiol Aging. 2024 Nov 20:146:38-47. doi: 10.1016/j.neurobiolaging.2024.11.006. Online ahead of print.

Authors

Floor A S de Kort¹, Elisabeth J Vinke², Ewoud J van der Lelij³, Devasuda Anblagan⁴, Mark E Bastin⁴, Alexa Beiser⁵, Henry Brodaty⁶, Nishi Chaturvedi⁷, Bastian Cheng⁸, Simon R Cox⁹, Charles DeCarli¹⁰, Christian Enzinger¹¹, Evan Fletcher¹⁰, Richard Frayne¹², Marius de Groot¹³, Felicia Huang⁷, M Arfan Ikram¹⁴, Jiyang Jiang⁶, Bonnie Y K Lam¹⁵, Pauline Maillard¹⁰, Carola Mayer⁸, Cheryl R McCreary¹², Vincent Mok¹⁵, Susana Muñoz Maniega⁴, Marvin Petersen⁸, Genady Roshchupkin², Perminder S Sachdev⁶, Reinhold Schmidt¹¹, Stephan Seiler¹¹, Sudha Seshadri¹⁶, Carole H Sudre¹⁷, Götz Thomalla⁸, Raphael Twerenbold¹⁸, Maria Valdés Hernández⁴, Meike W Vernooij², Joanna M Wardlaw¹⁹, Wei Wen⁶, Hugo J Kuijf²⁰, Geert Jan Biessels³, J Matthijs Biesbroek²¹

Affiliations

¹ Department of Neurology, University Medical Center Utrecht Brain Center, Utrecht, the Netherlands. Electronic address: f.a.s.dekort-3@umcutrecht.nl.
² Department of Radiology & Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands; Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
³ Department of Neurology, University Medical Center Utrecht Brain Center, Utrecht, the Netherlands.
⁴ Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
⁵ Department of Biostatistics, Boston University, Boston, USA.
⁶ Centre for Healthy Brain Ageing (CHeBA), Discipline of Psychiatry and Mental Health, School of Clinical Medicine, UNSW Sydney, Sydney, Australia.
⁷ MRC Unit for Lifelong Health and Ageing, University College London, London, UK.
⁸ Department of Neurology, University Medical Hospital Hamburg-Eppendorf, Hamburg, Germany.
⁹ Lothian Birth Cohorts, Department of Psychology, University of Edinburgh, Edinburgh, UK.
¹⁰ Department of Neurology, University of California Davis, Sacramento, USA.
¹¹ Department of Neurology, Medical University Graz, Graz, Austria.
¹² Department of Clinical Neurosciences, University of Calgary, Calgary, Canada; Department of Radiology, University of Calgary, Calgary, Canada.
¹³ Department of Radiology & Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
¹⁴ Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
¹⁵ Division of Neurology, Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, China.
¹⁶ Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health Science Center, San Antonio, USA.
¹⁷ MRC Unit for Lifelong Health and Ageing, University College London, London, UK; Centre for Medical Image Computing, University College London, London, UK; School of Biomedical Engineering & Imaging Sciences, King's College London, UK.
¹⁸ Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; DZHK (German Centre for Cardiovascular Research) partner site, Hamburg, Germany.
¹⁹ Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK; UK Dementia Research Institute, University of Edinburgh, Edinburgh, UK.
²⁰ Image Sciences Institute, University Medical Center Utrecht, Utrecht, the Netherlands.
²¹ Department of Neurology, University Medical Center Utrecht Brain Center, Utrecht, the Netherlands; Department of Neurology, Diakonessenhuis Hospital, Utrecht, the Netherlands.

PMID: 39602940
DOI: 10.1016/j.neurobiolaging.2024.11.006

Abstract

White matter hyperintensities (WMH) increase with age, with marked interindividual variation. There is a need for normative data by age and sex, to improve individualized WMH burden assessment. In this study, we pooled cross-sectional data from 15 population-based cohorts (14,876 nondemented individuals, age 18-97 years), through the Meta VCI Map consortium. Whole brain and tract-specific MRI-assessed WMH volumes were calculated in MNI-152 space. We used quantile regression to create centile curves of WMH volume versus age, stratified by sex. Total WMH volume and interindividual variance increased exponentially with age for both sexes, with females showing higher WMH volumes. WMH volume increase with aging was not uniform across the white matter, but instead followed one of three different patterns depending on location. Age- and sex-specific normative data for total and regional WMH volumes were created. Our study provides detailed information on the normal distribution of total and regional WMH volumes across adulthood. The normative data enable a quantitative approach to interpreting total and regional WMH volumes in clinical practice and research settings.

Keywords: Aging; Cerebral small vessel disease; MRI; Normative data; Population-based; White matter hyperintensities.