@article{861418132ff54839b3c940030bab1301,
title = "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{\textquoteright}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.",
keywords = "Cognitive impairment, Functional connectivity, Hypertension, White matter lesions",
author = "Chintan Shah and Dhivya Srinivasan and Guray Erus and Schmitt, {James E.} and Adhish Agarwal and Cho, {Monique E.} and Lerner, {Alan J.} and Haley, {William E.} and {Kurella Tamura}, Manjula and Christos Davatzikos and Bryan, {Robert N.} and Yong Fan and Nasrallah, {Ilya M.}",
note = "Funding Information: We also acknowledge the support from the following CTSAs funded by NCATS: Funding Information: CWRU: UL1TR000439; OSU: UL1RR025755; U Penn: UL1RR024134 and UL1TR000003; Boston: UL1RR025771; Stanford: UL1TR000093; Tufts: UL1RR025752, UL1TR000073, and UL1TR001064; University of Illinois: UL1TR000050; University of Pittsburgh: UL1TR000005; UT Southwestern: 9U54TR000017-06; University of Utah: UL1TR000105-05; Vanderbilt University: UL1 TR000445; George Washington University: UL1TR000075; University of CA, Davis: UL1 TR000002; University of Florida: UL1 TR000064; University of Michigan: UL1TR000433; Tulane University: P30GM103337 COBRE Award NIGMS. CS partially supported by NIH T32 Training Grant EB004311 and Radiological Society of North America fellow research grant. MKT was supported by R01 DK092241. Funding Information: The Systolic Blood Pressure Intervention Trial is funded with Federal funds from the National Institutes of Health (NIH), including the National Heart, Lung, and Blood Institute (NHLBI); the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); the National Institute on Aging (NIA); and the National Institute of Neurological Disorders and Stroke (NINDS), under Contract Numbers HHSN268200900040C, HHSN268200900046C, HHSN268200900047C, HHSN268200900048C, and HHSN268200900049C, and Inter-Agency Agreement Number A-HL-13-002-001. It was also supported in part with resources and use of facilities through the Department of Veterans Affairs. The SPRINT investigators acknowledge the contribution of study medications (azilsartan and azilsartan combined with chlorthalidone) from Takeda Pharmaceuticals International, Inc. All components of the SPRINT study protocol were designed and implemented by the investigators. The investigative team collected, analyzed, and interpreted the data. All aspects of manuscript writing and revision were carried out by the coauthors. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, the US Department of Veterans Affairs, or the United States Government. For a full list of contributors to SPRINT, please see the supplementary acknowledgement list: SPRINT Acknowledgment . Funding Information: Institutional review boards at all clinical sites participating in the SPRINT approved the trial protocol for enrollment and data acquisition, and all participants signed written informed consent. SPRINT was sponsored by the National Institutes of Health. Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.",
year = "2021",
month = jun,
doi = "10.1007/s00234-020-02614-6",
language = "English (US)",
volume = "63",
pages = "913--924",
journal = "Neuroradiology",
issn = "0028-3940",
publisher = "Springer Verlag",
number = "6",
}