Association of Increased Brain Iron Levels With Anxiety and Motor Dysfunction in Cerebral Small Vessel Disease

This study explored the relationships between brain iron levels, emotion, and cognitive and motor function in cerebral small vessel disease (CSVD) patients using quantitative susceptibility mapping (QSM).

A total of 208 subjects were enrolled in this study. A brain QSM map was calculated from multiecho GRE data via morphology-enabled dipole inversion with an automatic uniform cerebrospinal fluid zero reference algorithm (MEDI+0). Multiple linear regression analysis was applied to explore the clinical factors influencing cerebral susceptibility in CSVD patients. Correlation analysis and pathway-specific mediation effects between brain iron levels and motor function were investigated.

There were significant differences in the MoCA scores, depression scores, five-repetition sit-to-stand test (5R-STS) time, and susceptibility values of the caudate nucleus and putamen among the three groups (p < 0.05, FDR correction). Age and history of diabetes played crucial roles in brain iron levels in the caudate nucleus and putamen, which may increase iron levels in the basal ganglia, associated with cognitive decline. Notably, the susceptibility values of the left caudate nucleus and putamen were positively correlated with the 5R-STS time in CSVD subjects, and there were significant mediating effects of anxiety on the prediction of motor dysfunction with respect to iron levels in the left putamen in CSVD patients.

Age, diabetes status, and anxiety may serve as effective intervention targets for individuals with CSVD, especially individuals with cognitive and motor dysfunction. A greater brain iron burden may be a quantitative imaging marker of cognitive and motor dysfunction in CSVD patients.

ISRCTN20008650.