Ageing and brain white matter structure in 3,513 UK Biobank participants

ABSTRACT Quantifying the microstructural properties of the human brain’s connections is necessary for understanding normal ageing and disease states. We examined brain white matter MRI data in 3,513 generally healthy people aged 45-75 years from the UK Biobank sample. Using conventional water diffusion measures and newer, as-yet rarely-studied indices from neurite orientation dispersion and density imaging (NODDI), we document large age differences in white matter microstructure. Mean diffusivity was the most age-sensitive diffusion measure, with negative age associations strongest in the thalamic radiation and association fibres. Inter-individual differences in white matter microstructure across brain tracts become increasingly correlated in older age. This connectivity ‘de-differentiation’ may reflect an age-related aggregation of systemic detrimental effects on the brain. We report several other novel results, including comparative age associations with volumetric indices and associations with hemisphere and sex. Results from this unusually large, single-scanner sample provide one of the most definitive characterisations to date of age differences in major white matter tracts in the human brain. Abbreviations Tracts AR acoustic radiation ATR anterior thalamic radiation CingG cingulum bundle; gyrus CingPH cingulum gyrus; parahippocampal CST corticospinal tract FMaj forceps major FMin forceps minor IFOF inferior fronto-occipital fasciculus ILF inferior longitudinal fasciculus MCP middle cerebellar peduncle ML medial lemniscus PTR posterior thalamic radiation SLF superior longitudinal fasciculus STR superior thalamic radiation Unc uncinate fasciculus Measures of white matter microstructure FA fractional anisotropy ICVF intracellular volume fraction ISOVF isotropic volume fraction MD mean diffusivity NODDI neurite orientation dispersion and density imaging OD orientation dispersion