Association of MRI parameters of brain waste clearance function with cortisol and inflammatory markers in middle-aged and older adults with major depressive disorder.

BACKGROUND

Suicide risk remains high in middle-aged and older adults with major depressive disorder (MDD). Dysregulation of cortisol (CORT) and neuroinflammation may impair glymphatic clearance, but their effects in this population are unclear.

METHODS

Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index, choroid plexus volume (CPV), free water (FW) in white matter, and enlarged perivascular space (EPVS) grading of 20 MDD patients with elevated CORT (high-CORT), 39 MDD with normal CORT levels (normal-CORT), and 29 healthy controls (HCs) were compared. Inflammatory indices included the neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), aggregate index of systemic inflammation (AISI), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR). MRI parameters were also correlated with inflammatory indices and neuropsychological scales.

RESULTS

After controlling for age, gender, ACTH and HAMD-sleep disturbance, high-CORT group exhibited the lowest DTI-ALPS index (p < 0.01), significantly higher CPV (p = 0.04) compared to HCs, and tended to be higher BG EPVS grading compared to normal-CORT (p = 0.02). The DTI-ALPS index was negatively correlated with depression severity and HAMD-cognitive impairment (r ranging from -0.437 to -0.300; p ranging from 0.001 to 0.031). Moreover, the DTI-ALPS index was negatively associated with NLR (r = -0.277, p = 0.047). Additionally, CPV was positively correlated with multiple inflammatory indices (r ranging from 0.380 to 0.595, all p ≤ 0.01).

CONCLUSION

Significant differences in MRI-based markers of brain metabolic waste clearance were observed among middle-aged and older MDD patients with varying cortisol levels and HCs. These alterations were linked to depressive symptoms, cognitive impairment, and inflammation markers.