Disentangling the pathologies linking white matter hyperintensity and geriatric depressive symptoms in subjects with different degrees of vascular impairment

Background: White matter hyperintensity (WMH) is closely associated with geriatric depressive symptoms, but its underlying neural mechanism is unclear. We aim to disentangle the contribution of vascular degeneration and fiber disruption to depressive symptoms in elderly subjects at different clinical status. Methods: One hundred and thirty-three normal elderly subjects, as well as 43 patients with cerebral small vessel disease (CSVD) were included. The Hamilton Depression Rating Scale (HAMD) was used to measure depressive symptoms. Based on the diffusion tensor imaging data, a free water elimination analytical model was adopted to reflect fiber tract disruption (measure: tissue fractional anisotropy, tFA) and increased white matter water content (measure: free water fraction, FW). Results: We found that WMH severity was significantly correlated with decreased tFA and increased FW in all subjects. In normal elderly subjects, the HAMD score was correlated with mean tFA, but not FW. Compared to the traditional fractional anisotropy measure, tFA showed stronger correlation with clinical symptoms. In CSVD subjects, the correlation was only significant for FW, and marginally significant for tFA. Limitations: Most subjects had only mild to moderate depressive symptoms. Further validation in patients with major depressive disorder is needed to confirm these findings. Conclusions: The neural mechanisms of depressive symptoms may be different in elderly people with or without severe vascular damage. The free water elimination model may disentangle the effects of fiber disruption and increased free water, providing sensitive imaging markers that could potentially be used on monitoring disease treatment.