Sex differences in interrelationships between arterial stiffness, carotid intima-media thickness, white matter hyperintensities, depression and cognition: A UK Biobank study

Abstract Objective To explore sex differences in the associations between arterial stiffness index, carotid intima-media thickness, white matter hyperintensities, depression and cognition. Methods UK Biobank is a population-based cohort study of 502,664 healthy community dwelling adults aged 37-73 years. A select number of participants were recalled to participate in an online reassessment and imaging study, both of which included repeat cognitive assessments. A total of 7,394 volunteers aged 45-73 years (55% female) participated in the imaging visit and completed the self-report mental health questionnaire in the online follow-up were included in the analyses reported here. The main outcome measure of depression was measured using the PHQ-9 and cognition was assessed through measures of reaction time, verbal-numeric reasoning and visual memory. Pulse wave velocity (PWV) was assessed non-invasively using finger photoplethysmography, carotid intima-media thickness (CIMT) with automated ultrasound, and white matter hyperintensity volume with combined T1 and T2-weighted fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI). Results Cross-sectionally, greater arterial stiffness was associated with greater depression in men but with better cognition in women. When white matter hyperintensities burden was added to the model, it mediated the relationships of carotid intima-media thickness with depression and cognition only in men. Conclusions We report sex differences in brain microvascular changes, depression and cognition in ageing, and suggest that they may be partly explained by sex-specific effects of vascular ageing. Summary boxes Section 1: What is already known on this topic Arterial stiffness and carotid intima-media thickness are two non-invasive vascular ageing markers that have been shown to be associated with depression, cognitive impairment and dementia. Some studies report sex differences in arterial stiffness and carotid intima-media thickness. There is, however, a paucity of research on sex differences in the associations between these vascular ageing markers, white matter hyperintensities, depression and cognition. Section 2: What this study adds Cross-sectionally, greater arterial stiffness was associated with greater depression in men but with better cognition in women. When white matter hyperintensities burden was added to the model, it mediated the relationships of carotid intima-media thickness with depression and cognition only in men. Our findings add to the existing evidence base of sex differences in brain microvascular changes, depression and cognition in ageing, and suggest that they may be partly explained by sex-specific effects of vascular ageing.