A Comprehensive Analysis of the Association Between Blood Pressure Variability, Mental Health and Cognitive Functioning

Blood pressure has a critical role in supplying oxygenated blood to the brain and is one of the human body’s four vital signs. Though blood pressure naturally fluctuates to some degree, excessive aberrations, known as blood pressure variability (BPV), have emerged as a potential correlate of poorer brain health offering incremental information beyond a person’s average blood pressure. Elevated BPV is consistently associated with stroke in aetiological and prognostic studies. Higher BPV has also been implicated in cerebrovascular and cerebral small vessel diseases, brain morphology, cerebrovascular reactivity, as well as impairments in cognitive function, especially executive function and psychomotor performance. Late-onset depression and anxiety are also prevalent in cerebrovascular disease populations and are linked to changes in the brain’s white matter and disruptions to the brain’s fronto-striatal and central autonomic network. In terms of the latter, it remains largely unknown whether BPV quantified centrally from the heart’s aorta is associated with cognitive function, with most research to date exploring BPV obtained from brachial cuff measures. Previous research on BPV has methodological differences in BPV metrics and inconsistencies in reported effect sizes. Through three distinct studies, this thesis addresses current gaps by examining how 24-hour central and brachial BPV phenotypes are associated with cognitive function, depression, anxiety and sleep quality, contributing to understanding cardiovascular, cognitive, and mental health.<br>
Study 1 synthesized empirical evidence on the relationship between BPV with depression and anxiety through a systematic review. Of 14 articles reporting on 13 samples (n = 5055), three studies reported linear associations between systolic BPV and anxiety. Mixed results were observed across depression studies, with inconsistencies and variations in the direction and strength of association, highlighting a need for further cross-sectional study on BPV in relation to depression and anxiety symptoms. <br>
Study 2 employed a cross-sectional design (N = 88, Mage = 57.6) to examine the relationship between central and brachial BPV phenotypes and symptoms of depression, anxiety and sleep quality, using a 24-hour ambulatory BP monitor (ABPM). Spearman’s rho and multiple regression analyses revealed significant negative associations between central systolic BPV and anxiety (p=0.01, rs = -0.27), and symptoms of hopelessness (p=0.04, rs = -0.29). The coefficient of variation (CV) in central pulse pressure (PP) was negatively associated with sleep-related issues, including interruptions and length of difficulties. Brachial BPV showed no significant associations with depression or anxiety and less associations with sleep quality, suggesting central BPV may be more directly associated with depression, anxiety, and sleep quality compared to brachial BPV metrics.
Study 3 explored the relationship between BPV and cognition (n = 88, males = 61%). Spearman’s correlations revealed negative associations between BPV phenotypes and executive functioning and memory. Multiple regression analyses revealed specific associations, with the CV in Central Augmentation Index (AIx) associated with lower executive function and memory performance (β = -0.06, p=0.03; β = -0.25, p=0.04 respectively). Additionally, the CV in central Mean Arterial Pressure (MAP) and PP were domain-specific, with MAP negatively associated with executive function (β = -0.21, p=0.03) and PP with memory performance (β = -0.33, p=0.04). <br>
Together, the findings from this research suggest that BPV measured centrally is more consistently associated with cognitive function than brachial measures of BPV. The association between central and brachial BPV with symptoms of depression and anxiety was inconsistent, raising the possibility that purported associations between BPV and cognitive function are largely independent of depression and anxiety. Future research could consider longitudinal ABPM monitoring for cognitive decline, quantifying additional metrics of BPV such as average real variability, and consider the possibility for reverse causation.