Blood pressure, executive function, and network connectivity in middle-aged adults at risk of dementia in late life

Lisanne M. Jenkins, Alexandr Kogan, Matthew Malinab, Carson Ingo, Sanaz Sedaghat, Nick R. Bryan, Kristine Yaffe, Todd B. Parrish, Alexander J. Nemeth, Donald M. Lloyd-Jones, Lenore J. Launer, Lei Wang, Farzaneh Sorond

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7 Scopus citations


Midlife blood pressure is associated with structural brain changes, cognitive decline, and dementia in late life. However, the relationship between early adulthood blood pressure exposure, brain structure and function, and cognitive performance in midlife is not known. A better understanding of these relationships in the preclinical stage may advance our mechanistic understanding of vascular contributions to late-life cognitive decline and dementia and may provide early therapeutic targets. To identify resting-state functional connectivity of executive control networks (ECNs), a group independent components analysis was performed of functional MRI scans of 600 individuals from the Coronary Artery Risk Development in Young Adults longitudinal cohort study, with cumulative systolic blood pressure (cSBP) measured at nine visits over the preceding 30 y. Dual regression analysis investigated performance-related connectivity of ECNs in 578 individuals (mean age 55.5 ± 3.6 y, 323 female, 243 Black) with data from the Stroop color–word task of executive function. Greater connectivity of a left ECN to the bilateral anterior gyrus rectus, right posterior orbitofrontal cortex, and nucleus accumbens was associated with better executive control performance on the Stroop. Mediation analyses showed that while the relationship between cSBP and Stroop performance was mediated by white matter hyperintensities (WMH), resting-state connectivity of the ECN mediated the relationship between WMH and executive function. Increased connectivity of the left ECN to regions involved in reward processing appears to compensate for the deleterious effects of WMH on executive function in individuals across the burden of cumulative systolic blood pressure exposure in midlife.

Original languageEnglish (US)
Article numbere2024265118
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number37
StatePublished - Sep 14 2021
Externally publishedYes

Bibliographical note

Funding Information:
ACKNOWLEDGMENTS. This manuscript has been reviewed by CARDIA for scientific content. This study was supported by the National Institute of Neurological Disorders and Stroke (research grant R01-NS085002). The CARDIA study is conducted and supported by awards from the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (HHSN268201800005I and HHSN268201800007I), Northwestern University (HHSN268201800003I), the University of Minnesota (HHSN268201800006I), and the Kaiser Foundation Research Institute (HHSN268201800004I). CARDIA was also partially supported by the Intramural Research Program of the National Institute on Aging (NIA) and an intra-agency agreement between the NIA and the NHLBI (AG0005). S.S. is supported by a Rubicon fellowship from the Netherlands Organization for Scientific Research.

Publisher Copyright:
© 2021 National Academy of Sciences. All rights reserved.


  • Executive function
  • FMRI
  • Resting-state connectivity
  • Systolic blood pressure
  • White matter hyperintensities


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