Age- and Sex-Related Variations in the Brain White Matter Fractal Dimension Throughout Adulthood: An MRI Study

PURPOSE: To observe age- and sex-related differences in the complexity of the global and hemispheric white matter (WM) throughout adulthood by means of fractal dimension (FD). METHODS: A box-counting algorithm was used to extract FD from the WM magnetic resonance images of 209 healthy adults from three structural layers, including general (gFD), skeleton (sFD), and boundaries (bFD). Model selection algorithms and statistical analyses, respectively, were used to examine the patterns and significance of the changes. RESULTS: gFD and sFD showed inverse U-shape patterns with aging, with a slighter slope of increase from young to mid-age and a steeper decrease to the old. bFD was less affected by age. Sex differences were evident, specifically in gFD and sFD, with men showing higher FDs. Age × sex interaction was significant mainly in the hemispheric analysis, with men undergoing sharper age-related changes. After adjusting for the volume effect, age-related results remained approximately the same, but sex differences changed in most of the features, with women indicating higher values, specifically in the left hemisphere and boundaries. Right hemisphere was still more complex in men. CONCLUSIONS: This study is the first that investigates the WM FD spanning adulthood, treating age both as a continuous and categorical variable. We found positive correlations between FD and volume, and our results show similarities with those investigating small-world properties of the brain networks, as well as those of functional complexity and WM integrity. These suggest that FD could yield a highly compact description of the structural changes and also might inform us about functional and cognitive variations.