Association between deep gray matter iron deposition, white matter hyperintensity, and hypertensive cognitive...

Deep gray matter (DGM) iron deposition and white matter hyperintensity (WMH) often occur simultaneously in hypertensive patients. However, their relationship and effect on cognition in hypertension remain unclear. We aimed to investigate the correlation between DGM iron deposition, WMH, and cognitive impairment.

A total of 105 hypertensive patients and 31 age-, gender-, and education-matched healthy controls (HCs) were prospectively recruited for the study; the patients were divided into the hypertension with cognitive impairment (HTN-CI) group (n=55) and the hypertension without cognitive impairment (HTN-NCI) group (n=50). All participants underwent strategically acquired gradient echo (STAGE) imaging, and quantitative susceptibility mapping (QSM) was obtained. The global region (RI) and high-iron content region (RII) susceptibilities of the DGM were measured. The associations between WMH, iron deposition, and cognitive impairment were analyzed by partial correlation, univariate, multivariate linear regression, and exploratory mediation analyses.

The RI or RII analysis results showed that the susceptibilities of the bilateral caudate nucleus (CN) head, thalamus (TH), and putamen (PU) differed significantly among the three groups (all P<0.05). Further, the RII susceptibilities of the bilateral red nucleus (RN) (left, r=0.312, P=0.023; right, r=0.336, P=0.014) and substantia nigra (SN) (left, r=0.347, P=0.011; right, r=0.316, P=0.021) were positively associated with the WMH scores. After adjusting for confounders, the model showed that decreased cognitive performance was associated with both increased WMH (β=-0.303, P=0.007) and susceptibilities of the left CN head (β=-0.450, P<0.001). WMH scores did not exhibit a significant mediation effect on the relationship between susceptibilities of the left CN head and cognition (P>0.05).

Both DGM iron deposition and WMH were found to be more pronounced in hypertension, and were negatively associated with cognitive function.