Changes in brain functional connectivity and cognition related to white matter lesion burden in hypertensive patients from SPRINT

Abstract

Purpose: Hypertension is a risk factor for cognitive impairment; however, the mechanisms leading to cognitive changes remain unclear. In this cross-sectional study, we evaluate the impact of white matter lesion (WML) burden on brain functional connectivity (FC) and cognition in a large cohort of hypertensive patients from the Systolic Blood Pressure Intervention Trial (SPRINT) at baseline.

Methods: Functional networks were identified from baseline resting state functional MRI scans of 660 SPRINT participants using independent component analysis. WML volumes were calculated from structural MRI. Correlation analyses were carried out between mean FC of each functional network and global WML as well as WML within atlas-defined white matter regions. For networks of interest, voxel-wise-adjusted correlation analyses between FC and regional WML volume were performed. Multiple variable linear regression models were built for cognitive test performance as a function of network FC, followed by mediation analysis.

Results: Mean FC of the default mode network (DMN) was negatively correlated with global WML volume, and regional WML volume within the precuneus. Voxel-wise correlation analyses revealed that regional WML was negatively correlated with FC of the DMN's left lateral temporal region. FC in this region of the DMN was positively correlated to performance on the Montreal Cognitive Assessment and demonstrated significant mediation effects. Additional networks also demonstrated global and regional WML correlations; however, they did not demonstrate an association with cognition.

Conclusion: In hypertensive patients, greater WML volume is associated with lower FC of the DMN, which in turn is related to poorer cognitive test performance.

Trial registration: NCT01206062.

Keywords: Cognitive impairment; Functional connectivity; Hypertension; White matter lesions.

Conflict of interest statement

Competing interests The authors declare no relevant financial or other conflicting interests. RN Bryan declares equity in Galileo CDS, Inc. (Founder and Chairman).

Figures

Fig. 1

Default mode network (DMN). a Masked DMN map. B Connectivity—rWML correlation t map, indicating regions within the network where FC is correlated to rWML. Shades of red/yellow are positive and shades of blue are negative correlations. c Scatter plot of rWML vs. mean connectivity score. d Scatter plot of rWML vs. WML-related cluster connectivity. DMN, default mode network; MCS, mean connectivity score; rWML, regional white matter lesion volume; WCC, WML-related cluster connectivity

Fig. 2

Results from mediation analysis. The conditional process diagrams present standardized β FC on rWML-cognitive relationships in the DMN. The mediating effects of both cluster connectivity (WCC, a) and mean connectivity (MCS, b) are provided. The average causal mediation effects (ACME), average direct effects (ADE), and total effect point estimates are shown, as are 95% confidence intervals. DMN, default mode network; MCS, mean connectivity score; rWML, regional white matter lesion volume; WCC, WML-related cluster connectivity; MoCA. Montreal Cognitive Assessment