Abstract

Abstract Background In our rapidly ageing society, dementia and neurocognitive decline are significant global public health problems. Blood pressure (BP), an established cardiovascular risk factor, has been extensively studied with respect to brain structure and function; however, findings across the literature differ depending on the BP component in consideration, and the use of brachial rather than central BP. Purpose We set out to assess associations between detailed measures of brain structure and function with comprehensive measures of central and peripheral BP. Furthermore, we performed comprehensive mediation analyses on the associations to investigate potential micro and macro vascular mediatory pathways. Methods A community-based sample of 1438 individuals (69.7±6.2 years) from a tri-ethnic cohort. underwent vascular, cognitive and MRI based structural brain measures. BP measures included central (cSBP (Pulsecor)) and peripheral systolic BP (pSBP), diastolic BP (DBP), brachial (bPP) and central pulse pressure (cPP), and mean arterial pressure (MAP). Cognitive assessments comprised tests which explored global/overall function (CSID), executive function and memory. For brain structure, hippocampal brain volume was our key measure. Potential macro- and microvascular mediators included: arterial stiffness (cfPWV), carotid intima-media thickness, retinopathy, white matter hyperintensities and infarcts. Multivariable regression analyses were used to assess associations of BP components with cognitive function scores and brain volumes, adjusted for age, sex and ethnicity as well as macro- and microvascular risk factors. Multiple imputation was performed to account for missing data. Results After adjusting for age, sex and ethnicity, both cSBP and pSBP were negatively associated with memory (data are β±SE (z-score) −0.014±0.006, p=0.04), while DBP was positively associated with hippocampal volume (0.006±0.003, p=0.03). cPP was negatively associated with memory (−0.020±0.009, p=0.03), executive function (−0.018±0.006, p=0.002) and hippocampal volume (−0.007±0.003, p=0.005), while bPP was negatively associated with CSID (−0.008±0.004, p=0.04), memory (−0.020±0.008, p=0.02), executive function (−0.016±0.005, p=0.002) and hippocampal volume (−0.006±0.002, p=0.007). There was a stronger association between both PP measures and brain structure and function than with the other BP components, especially MAP. There was little difference in association between cPP and bPP measures with brain structure and function. Furthermore, these associations do not appear to be mediated by either macro- or microvascular disease. Conclusion These results suggest that there is a direct association between increased PP and a decline in brain structure and function. This implies that older patients with suboptimal PP control may be at increased risk of developing cognitive impairment and that measuring PP offers mechanistic information above and beyond conventional BP measures. Acknowledgement/Funding Wellcome Trust, British Heart Foundation

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