Microstructural brain assessment in late-life depression and apathy using diffusion MRI multi-compartments models associated with tractometry

Abstract Late-life depression is a common disorder in the elderly, difficult to treat, where apathy contributes to a poor prognosis. Despite its severity and frequency, the pathophysiology of LLD remains complex and its exploration challenging. While white matter (WM) damages have been assessed using diffusion tensor imaging, this model cannot correctly represent the WM microstructure. We hypothesized that using a more complex multi-compartment model, never used on LLD, would better describe the WM microstructure. In this article, we performed a tract-based approach to investigate novel diffusion-model biomarkers of LLD and apathy, by interpolating the microstructural metrics directly along the fibers. We performed a multivariate statistical analysis along the fiber, combined with a principal component analysis for dimensional data reduction. Then, we tested the utility of our framework by showing classical modifications in LDD. Finally, we aimed to investigate the relationship between apathy and microstructure in different fibers. Our study suggests that new tracts, such as striato-premotor, may be involved in LLD and apathy, which has not been observed in previous studies. We also identified modifications of inflammation metrics in 5 different tracts, already reported in dementia, which may contribute to the cognitive decline observed with apathy.