DOI: 10.1002/alz.073654 ISSN: 1552-5260

A multi‐center pooled analysis of individual imaging data of 14,876 non‐demented participants to create normative data for total and regional white matter hyperintensity volumes to support dementia diagnosis.

Floor de Kort, J. Matthijs Biesbroek,
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology



White matter hyperintensities (WMH) are a common manifestation of cerebral small vessel disease and a major cause of cognitive decline and dementia. Recent studies show that the cognitive impact of WMH depends on their location in strategic white matter regions. WMH are highly prevalent among asymptomatic individuals and increase with age. For dementia diagnosis, identifying patients with excessive total and regional (strategic) WMH therefore requires age‐ and sex specific norms, which are currently lacking. We aimed to obtain normative data for both total and regional WMH volumes in non‐demented community‐dwelling individuals.


We harmonized individual person data from 15 cohorts, through the Meta VCI Map consortium ( Cohorts were eligible for inclusion if participants were recruited from the population, underwent brain MRI (with availability of FLAIR and T1 sequences) and cognitive testing. Cohorts that recruited patients based on the presence of cognitive symptoms were not eligible for inclusion. Individuals fulfilling criteria for dementia were excluded. WMH were segmented and registered to the MNI‐152 template. WMH maps were used to calculate total WMH volume and regional WMH volumes in 20 pre‐specified white matter tracts. Normative data on WMH volumes were derived from observed values in 5‐years age bands and reported as cut‐off values for percentiles. All volumes are normalized WMH volumes (i.e. calculated on the MNI‐152 template).


We analyzed 14,876 individuals with a mean age of 63.9 years (SD 11.9), 52% of whom were female. Median WMH volume was 2.0 mL (normalized, IQR 3.9) for the total sample. Median WMH volume increased with age, from 0.25 mL (<45 years) to 7.3 and 12.8 mL (>85 years) for men and women respectively. The table shows total WMH volume cut‐off values for percentiles, stratified for age and sex (cut‐off values for regional WMH volumes not shown due to abstract size constraints).


This study provides age‐ and sex‐specific normative data on total and regional WMH volumes. This enables an individualized approach to interpreting total and regional WMH burden to support diagnosis in clinical practice.

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