Associations of depression and perceived physical fatigability with white matter integrity in older adults

•Using diffusion MRI on the white matter tracts of the late-life depressed older adults in the community, those with depression had lower quantitative anisotropy (QA) in left superior longitudinal Fasciculus-II, but those with greater perceived physical fatigability had lower QA in more widespread brain regions.•For tracts associated physical fatigability, lower QA in the left acoustic radiation and left superior thalamic radiation negatively correlated with high blood sugar.•For tracts associated with depression, lower QA in the left SLF-II correlated with higher bilirubin level.•Depression and fatigability are associated with differential changes in white matter integrity. Nevertheless, they may share a common underlying inflammatory mechanism. Fatigability is prevalent in older adults. However, it is often associated with depressed mood. We aim to investigate these two psychobehavioral constructs by examining their underpinning of white matter structures in the brain and their associations with different medical conditions. Twenty-seven older adults with late-life depression (LLD) and 34 cognitively normal controls (CN) underwent multi-shell diffusion MRI. Fatigability was measured with the Pittsburgh Fatigability Scale. We examined white matter integrity by measuring the quantitative anisotropy (QA), a fiber tracking parameter with better accuracy than the traditional imaging technique. We found those with LLD had lower QA in the 2nd branch of the left superior longitudinal fasciculus (SLF-II), and those with more physical fatigability had lower QA in more widespread brain regions. In tracts associated with more physical fatigability, the lower QA in left acoustic radiation and left superior thalamic radiation correlated with higher blood glucose (r = - 0.46 and - 0.49). In tracts associated with depression, lower QA in left SLF-II correlated with higher bilirubin level (r = - 0.58). Depression and fatigability were associated with various white matter integrity changes, which correlated with biochemistry biomarkers all related to inflammation.