Hobden, Georgina; Reid, Graham; Chiesa, Scott T; Wang, Congxiyu; Jobbins, Lucy; Mackay, Clare E; Hughes, Alun; ... Suri, Sana; + view all Hobden, Georgina; Reid, Graham; Chiesa, Scott T; Wang, Congxiyu; Jobbins, Lucy; Mackay, Clare E; Hughes, Alun; Ebmeier, Klaus P; Pitt, Jemma; Kivimäki, Mika; Singh-Manoux, Archana; Suri, Sana; - view fewer (2025) Associations of aortic and carotid artery health with cerebrovascular markers and cognition in older adults from the Whitehall II imaging study. BMC Medicine , 23 , Article 330. 10.1186/s12916-025-04105-y.

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Abstract

Background: Cardiovascular disease has been associated with an increased dementia risk, but the mechanisms are less clear. As such, this paper sought to examine associations between aortic/carotid artery measures in later-life with cerebrovascular reactivity (CVR), white matter hyperintensities (WMHs), and cognition.// Methods: 163 participants (25.8% female) from Whitehall II Imaging cohort completed two examinations (M±SD age 68.2±4.4 at Wave-1 and 76.9±4.5 at Wave-2), including neuropsychological assessments and 3T-FLAIR scans quantifying WMHs. Wave-2 additionally included vascular sonography and CVR quantification (mean % change BOLD signal change during CO2 challenge). Wave-2 factor scores of aortic and carotid arterial diameters, stiffness, and compliance were the exposure variables. Midlife Framingham Cardiovascular Risk Score (FRS) measured before Wave-1 was a potential effect modifier. WMH volume, grey matter CVR, cognitive factor scores (memory, working memory, executive function, visuospatial memory, fluency, lexical retrieval) at Wave-2, and changes in WMH and cognition between Wave-1 and Wave-2 were used as outcome variables.// Results: Larger aortic diameter (ß=0.38, SE=0.11) and greater aortic stiffness (ß=0.27, SE=0.10) were associated with larger carotid diameter, independently of body size. Higher midlife FRS was associated with larger aortic diameter, larger carotid diameter, and increased carotid stiffness in old age. We observed notable artery-brain associations, such that larger aortic (ß=0.17, SE=0.06) and carotid diameters (ß=0.11, SE=0.05) were associated with larger WMH lesion volumes. Larger aortic diameter (ß=0.08 SE=0.03) and lower carotid compliance (ß=-0.06, SE=0.02) at follow-up also associated with greater longitudinal increases in WMH volumes over the preceding 9 years. Higher stiffness and lower compliance of the aorta and carotid were associated with worse cognitive outcomes across a range of domains, and these associated were moderated by midlife FRS. Larger carotid diameter was associated with higher cerebrovascular reactivity (ß=0.02, SE=0.01), suggesting a potential compensatory pathway.// Conclusions: Adverse structural and functional changes in the aorta and carotid artery were inter-related and associated with vascular brain lesions, cerebrovascular reactivity, and poorer cognitive outcomes in older age.

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