Total and Structural Carotid Artery Stiffness Are Associated With Cognitive Decline and Structural Brain Abnormalities Related to Alzheimer Disease and Alzheimer Disease‐Related Dementias Pathology: The Multi‐Ethnic Study of Atherosclerosis

Background Arterial stiffness is associated with pathological changes underlying Alzheimer disease and related dementias. Total pulse wave velocity can be subdivided into 2 main mechanisms: structural arterial stiffness (S‐PWV) due to intrinsic remodeling of the artery wall and load‐dependent arteri...

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Main Authors: Jeremy R. Williams, Theodore M. DeConne, Ryan Pewowaruk, Claudia Korcarz, Jordan Tanley, Cynthia Carlsson, Susan R. Heckbert, Mohamad Habes, Ilya Nasrallah, Samuel N. Lockhart, José A. Luchsinger, Jingzhong Ding, Kathleen M. Hayden, Timothy M. Hughes, Adam D. Gepner
Format: Article
Language:English
Published: Wiley 2025-05-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
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Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.124.039925
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author Jeremy R. Williams
Theodore M. DeConne
Ryan Pewowaruk
Claudia Korcarz
Jordan Tanley
Cynthia Carlsson
Susan R. Heckbert
Mohamad Habes
Ilya Nasrallah
Samuel N. Lockhart
José A. Luchsinger
Jingzhong Ding
Kathleen M. Hayden
Timothy M. Hughes
Adam D. Gepner
author_facet Jeremy R. Williams
Theodore M. DeConne
Ryan Pewowaruk
Claudia Korcarz
Jordan Tanley
Cynthia Carlsson
Susan R. Heckbert
Mohamad Habes
Ilya Nasrallah
Samuel N. Lockhart
José A. Luchsinger
Jingzhong Ding
Kathleen M. Hayden
Timothy M. Hughes
Adam D. Gepner
author_sort Jeremy R. Williams
collection DOAJ
description Background Arterial stiffness is associated with pathological changes underlying Alzheimer disease and related dementias. Total pulse wave velocity can be subdivided into 2 main mechanisms: structural arterial stiffness (S‐PWV) due to intrinsic remodeling of the artery wall and load‐dependent arterial stiffness due to increased blood pressure. Methods and Results In this prospective cohort study, MESA (Multi‐Ethnic Study of Atherosclerosis) participants completed B‐mode carotid ultrasounds from which carotid total pulse wave velocity was calculated. S‐PWV was calculated by adjusting pulse wave velocity to 120/80 mmHg using a nonlinear pressure‐diameter relationship, and load‐dependent arterial stiffness was derived by subtracting S‐PWV from total pulse wave velocity. Participants had repeated cognitive assessments with the Cognitive Abilities Screening Instrument, Digit Symbol Coding, and Digit Span combined into a global cognitive composite (N=2489). Brain magnetic resonance imaging was used to generate total gray matter volume (N=906), white matter hyperintensity volume (N=896), and total white matter fractional anisotropy (N=810). Multivariable linear fixed and mixed effects regression models related standardized pulse wave velocity components to neuroimaging and cognitive decline parameters, respectively. Greater S‐PWV was associated with greater longitudinal cognitive decline in global cognitive composite score (β=–0.05, P=0.002) and subtests, whereas greater load‐dependent arterial stiffness was not associated with longitudinal cognitive decline. Greater S‐PWV was associated with lower gray matter volume (β=–3183.4, P=0.013) and higher log white matter hyperintensity volume (β=0.20, P<0.001), whereas load‐dependent arterial stiffness was associated with lower total white matter fractional anisotropy (β=–0.004, P≤0.001). Conclusions Higher structural stiffness of the carotid artery is associated with cognitive decline, whereas both structural and load‐dependent stiffness are associated with brain structural abnormalities common in Alzheimer disease‐related dementias.
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spelling doaj-art-0e279964c36448408a672370fb817db82025-08-20T02:26:28ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-05-0114910.1161/JAHA.124.039925Total and Structural Carotid Artery Stiffness Are Associated With Cognitive Decline and Structural Brain Abnormalities Related to Alzheimer Disease and Alzheimer Disease‐Related Dementias Pathology: The Multi‐Ethnic Study of AtherosclerosisJeremy R. Williams0Theodore M. DeConne1Ryan Pewowaruk2Claudia Korcarz3Jordan Tanley4Cynthia Carlsson5Susan R. Heckbert6Mohamad Habes7Ilya Nasrallah8Samuel N. Lockhart9José A. Luchsinger10Jingzhong Ding11Kathleen M. Hayden12Timothy M. Hughes13Adam D. Gepner14Department of Cardiovascular Medicine University of Wisconsin–School of Medicine and Public Health Madison WI USADepartment of Internal Medicine, Section on Gerontology and Geriatric Medicine Wake Forest School of Medicine Winton‐Salem NC USARyan Pewowaruk Research Consulting Madison WI USADepartment of Cardiovascular Medicine University of Wisconsin–School of Medicine and Public Health Madison WI USADepartment of Internal Medicine, Section on Gerontology and Geriatric Medicine Wake Forest School of Medicine Winton‐Salem NC USADepartment of Cardiovascular Medicine University of Wisconsin–School of Medicine and Public Health Madison WI USADepartment of Epidemiology University of Washington–School of Public Health Seattle WA USANeuroimage Analytics Laboratory, and Biggs Institute Neuroimaging Core Biggs Alzheimer’s Institute, University of Texas San Antonio Health Science Center San Antonio TX USAArtificial Intelligence in Biomedical Imaging Laboratory (AIBIL), Center for and Data Science for Integrated Diagnostics (AI2D), Perelman School of Medicine, University of Pennsylvania Philadelphia PA USADepartment of Internal Medicine, Section on Gerontology and Geriatric Medicine Wake Forest School of Medicine Winton‐Salem NC USADepartment of Medicine and Epidemiology Columbia University Irving Medical Center New York NY USADepartment of Internal Medicine, Section on Gerontology and Geriatric Medicine Wake Forest School of Medicine Winton‐Salem NC USADepartment of Social Sciences and Health Policy, Division of Public Health Sciences Wake Forest School of Medicine Winston‐Salem NC USADepartment of Internal Medicine, Section on Gerontology and Geriatric Medicine Wake Forest School of Medicine Winton‐Salem NC USADepartment of Cardiovascular Medicine University of Wisconsin–School of Medicine and Public Health Madison WI USABackground Arterial stiffness is associated with pathological changes underlying Alzheimer disease and related dementias. Total pulse wave velocity can be subdivided into 2 main mechanisms: structural arterial stiffness (S‐PWV) due to intrinsic remodeling of the artery wall and load‐dependent arterial stiffness due to increased blood pressure. Methods and Results In this prospective cohort study, MESA (Multi‐Ethnic Study of Atherosclerosis) participants completed B‐mode carotid ultrasounds from which carotid total pulse wave velocity was calculated. S‐PWV was calculated by adjusting pulse wave velocity to 120/80 mmHg using a nonlinear pressure‐diameter relationship, and load‐dependent arterial stiffness was derived by subtracting S‐PWV from total pulse wave velocity. Participants had repeated cognitive assessments with the Cognitive Abilities Screening Instrument, Digit Symbol Coding, and Digit Span combined into a global cognitive composite (N=2489). Brain magnetic resonance imaging was used to generate total gray matter volume (N=906), white matter hyperintensity volume (N=896), and total white matter fractional anisotropy (N=810). Multivariable linear fixed and mixed effects regression models related standardized pulse wave velocity components to neuroimaging and cognitive decline parameters, respectively. Greater S‐PWV was associated with greater longitudinal cognitive decline in global cognitive composite score (β=–0.05, P=0.002) and subtests, whereas greater load‐dependent arterial stiffness was not associated with longitudinal cognitive decline. Greater S‐PWV was associated with lower gray matter volume (β=–3183.4, P=0.013) and higher log white matter hyperintensity volume (β=0.20, P<0.001), whereas load‐dependent arterial stiffness was associated with lower total white matter fractional anisotropy (β=–0.004, P≤0.001). Conclusions Higher structural stiffness of the carotid artery is associated with cognitive decline, whereas both structural and load‐dependent stiffness are associated with brain structural abnormalities common in Alzheimer disease‐related dementias.https://www.ahajournals.org/doi/10.1161/JAHA.124.039925arterial stiffnesscognitionMESAMRI brain abnormalities
spellingShingle Jeremy R. Williams
Theodore M. DeConne
Ryan Pewowaruk
Claudia Korcarz
Jordan Tanley
Cynthia Carlsson
Susan R. Heckbert
Mohamad Habes
Ilya Nasrallah
Samuel N. Lockhart
José A. Luchsinger
Jingzhong Ding
Kathleen M. Hayden
Timothy M. Hughes
Adam D. Gepner
Total and Structural Carotid Artery Stiffness Are Associated With Cognitive Decline and Structural Brain Abnormalities Related to Alzheimer Disease and Alzheimer Disease‐Related Dementias Pathology: The Multi‐Ethnic Study of Atherosclerosis
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
arterial stiffness
cognition
MESA
MRI brain abnormalities
title Total and Structural Carotid Artery Stiffness Are Associated With Cognitive Decline and Structural Brain Abnormalities Related to Alzheimer Disease and Alzheimer Disease‐Related Dementias Pathology: The Multi‐Ethnic Study of Atherosclerosis
title_full Total and Structural Carotid Artery Stiffness Are Associated With Cognitive Decline and Structural Brain Abnormalities Related to Alzheimer Disease and Alzheimer Disease‐Related Dementias Pathology: The Multi‐Ethnic Study of Atherosclerosis
title_fullStr Total and Structural Carotid Artery Stiffness Are Associated With Cognitive Decline and Structural Brain Abnormalities Related to Alzheimer Disease and Alzheimer Disease‐Related Dementias Pathology: The Multi‐Ethnic Study of Atherosclerosis
title_full_unstemmed Total and Structural Carotid Artery Stiffness Are Associated With Cognitive Decline and Structural Brain Abnormalities Related to Alzheimer Disease and Alzheimer Disease‐Related Dementias Pathology: The Multi‐Ethnic Study of Atherosclerosis
title_short Total and Structural Carotid Artery Stiffness Are Associated With Cognitive Decline and Structural Brain Abnormalities Related to Alzheimer Disease and Alzheimer Disease‐Related Dementias Pathology: The Multi‐Ethnic Study of Atherosclerosis
title_sort total and structural carotid artery stiffness are associated with cognitive decline and structural brain abnormalities related to alzheimer disease and alzheimer disease related dementias pathology the multi ethnic study of atherosclerosis
topic arterial stiffness
cognition
MESA
MRI brain abnormalities
url https://www.ahajournals.org/doi/10.1161/JAHA.124.039925
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