Associations of blood pressure with brain free water and cognitive outcomes: a population-based study

The relationship between brain atrophy, free water (FW), and cognitive function in individuals with hypertension is not yet fully understood. This study aimed to delineate the associations between blood pressure (BP) and FW, and to characterize the spatial distribution of FW elevation as a neuroimaging marker in relation to hypertension-related brain health impairment.

This study recruited 984 participants from a community-based cohort. They were divided into normotensive, elevated and hypertensive groups. Neuroimaging data were collected once for brain macrostructure and microstructure. Cognition was assessed by the Montreal Cognitive Assessment (MoCA). Mediation analysis was employed to determine whether FW mediated the relationship between BP and cognition.

Elevated systolic BP (SBP) and diastolic BP (DBP) were correlated with increased total FW (SBP: r = 0.30, P < 0.001; DBP: r = 0.17, P < 0.001). In the three groups, an increase in FW of brain regions was significantly associated with a decrease in gray matter (β = -0.558; 95% CI, -0.766 to -0.349), white matter (β = -1.373; 95% CI, -1.621 to -1.126), and hippocampal (β = -0.449, 95% CI, -0.650 to -0.038) volumes. The MoCA score decreased with the increase of FW. FW partially mediated the relationships of SBP and DBP with MoCA score, accounting for 45.04% and 45.90% of the total effects, respectively.

FW elevation associated with higher BP is closely linked to poorer brain health and lower cognition. FW may serve as a candidate imaging marker of hypertension-related brain alterations.