Longitudinal aortic stiffness is associated with brain microstructure and cognition: A voxel‐wise magnetic resonance imaging study

Abstract

AbstractBackgroundAortic stiffness, assessed by carotid‐femoral pulse wave velocity (PWV), is closely linked with hypertension, heart disease and stroke. Recent research has suggested that rapid aortic stiffening may also be a risk factor for cognitive decline and dementia. However, the age of onset of this risk and its underlying brain physiology is unknown. We examined whether aortic stiffening over a 5‐year period in mid‐life affects later‐life brain structure and cognition in community‐dwelling adults.MethodData from 544 participants from the Whitehall II Imaging Sub‐study were analysed. Aortic PWV was measured at baseline in 2007‐09 (mean age 63.92±5.23) and at a 5‐year follow‐up visit in 2012‐13 (mean age 67.99±5.25) using applanation tonometry (SphygmoCor, AtCor Medical, Australia). After the latter visit, they also received cognitive tests and a 3T brain MRI scan (2012‐2016, mean age 69.82±5.23). Voxel‐based morphometry and tract‐based spatial statistics were used to extract grey matter (GM) volume, fractional anisotropy (FA), mean diffusivity (MD), and white matter hyperintensity (WMH) volumes. Baseline and follow‐up arterial stiffness were entered as predictors of MRI and cognitive outcomes in two separate general linear models, each adjusting for age, sex, education, mean arterial pressure, body mass index, socio‐economic status, scanner model, and follow‐up time interval.ResultHigher aortic stiffness at baseline was associated with significantly poor performance in semantic fluency (category ‘animals’, B(SE)=‐0.42(0.15), Bonferroni‐corrected p<0.008) and short‐term verbal memory (immediate recall on the Hopkins Verbal Learning Test‐R, B(SE)=‐0.36, (0.12), Bonferroni‐corrected p<0.008) at the time of the scan. Follow‐up aortic stiffness was associated with significantly lower FA and higher MD in widespread brain areas including the corpus callosum, corona radiata, cingulum, and superior longitudinal fasciculus (p<0.05, corrected for voxel‐wise comparisons). No significant associations with GM or WMH were observed.ConclusionElevated aortic stiffness after age 60 is associated with poor WM microstructural integrity and cognitive performance in older age independently of standard vascular risk factors, likely due to increased transmission of pulsatile energy to the delicate cerebral microvasculature. To offer cognitive benefit in older age, strategies to prevent arterial stiffening may be more effective in midlife than in later‐life.