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

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.