Chintan Shah1,2, Dhivya Srinivasan3,4, Guray Erus3,4, James E Schmitt3, Adhish Agarwal5, Monique E Cho5, Alan J Lerner6, William E Haley7, Manjula Kurella Tamura8,9, Christos Davatzikos3,4, Robert N Bryan10, Yong Fan3,4, Ilya M Nasrallah3,4. 1. Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA. shahc2@ccf.org. 2. Department of Radiology, Imaging Institute, Cleveland Clinic, 9500 Euclid Ave, Mail code L10-428, Cleveland, OH, 44195, USA. shahc2@ccf.org. 3. Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA. 4. Center for Biomedical Image Computing and Analytics, University of Pennsylvania, PA, Philadelphia, USA. 5. Division of Nephrology and Hypertension, University of Utah, Salt Lake City, UT, USA. 6. University Hospitals Cleveland Medical Center, Department of Neurology, Case Western Reserve University, Cleveland, OH, USA. 7. Department of Nephrology and Hypertension, Mayo Clinic, Jacksonville, FL, USA. 8. Division of Nephrology, Stanford University, Palo Alto, CA, USA. 9. VA Palo Alto Geriatric Research and Education Clinical Center, Palo Alto, CA, USA. 10. Dell Medical School, Department of Diagnostic Medicine, University of Texas at Austin, Austin, TX, USA.
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.
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.
Entities:
Keywords:
Cognitive impairment; Functional connectivity; Hypertension; White matter lesions
Authors: Malee S Fernando; Julie E Simpson; Fiona Matthews; Carol Brayne; Claire E Lewis; Robert Barber; Raj N Kalaria; Gill Forster; Filomena Esteves; Stephen B Wharton; Pamela J Shaw; John T O'Brien; Paul G Ince Journal: Stroke Date: 2006-04-20 Impact factor: 7.914