Faculty, Staff and Student Publications
Publication Date
5-6-2025
Journal
Scientific Data
Abstract
Age-related white matter (WM) microstructure maturation and decline occur throughout the human lifespan, complementing the process of gray matter development and degeneration. Here, we create normative lifespan reference curves for global and regional WM microstructure by harmonizing diffusion MRI (dMRI)-derived data from ten public datasets (N = 40,898 subjects; age: 3-95 years; 47.6% male). We tested three harmonization methods on regional diffusion tensor imaging (DTI) based fractional anisotropy (FA), a metric of WM microstructure, extracted using the ENIGMA-DTI pipeline. ComBat-GAM harmonization provided multi-study trajectories most consistent with known WM maturation peaks. Lifespan FA reference curves were validated with test-retest data and used to assess the effect of the ApoE4 risk factor for dementia in WM across the lifespan. We found significant associations between ApoE4 and FA in WM regions associated with neurodegenerative disease even in healthy individuals across the lifespan, with regional age-by-genotype interactions. Our lifespan reference curves and tools to harmonize new dMRI data to the curves are publicly available as eHarmonize ( https://github.com/ahzhu/eharmonize ).
Keywords
Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Female, Humans, Male, Middle Aged, Young Adult, Apolipoprotein E4, Brain, Diffusion Magnetic Resonance Imaging, Diffusion Tensor Imaging, Longevity, Reference Values, White Matter
DOI
10.1038/s41597-025-05028-2
PMID
40328780
PMCID
PMC12056076
PubMedCentral® Posted Date
5-6-2025
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Mental and Social Health Commons, Neurosciences Commons, Psychiatry Commons, Psychiatry and Psychology Commons