Brain-wide associations between white matter and age highlight the role of fornix microstructure in brain ageing

Identifying white matter (WM) microstructure parameters that reflect the underlying biology of the brain will advance our understanding of ageing and brain health. In this extensive comparison of brain age predictions and age-associations of WM features from different diffusion approaches, we analysed UK Biobank diffusion Magnetic Resonance Imaging (dMRI) data across midlife and older age (N = 35,749, 44.6 to 82.8 years of age). Conventional and advanced dMRI approaches were consistent in predicting brain age; with their WM-features similarly related to and predicted by age. However, brain age was estimated best when combining approaches, showing different aspects of WM to contribute to brain age. Fornix was found as the central region for brain age predictions across diffusion approaches. We encourage the application of multiple dMRI approaches for detailed insights into WM, and the further investigation of fornix as a potential biomarker of brain age and ageing.