Strong and specific associations between cardiovascular risk factors and white matter micro- and macrostructure in healthy aging.

Cardiovascular health declines with age, increasing the risk of hypertension and elevated heart rate in middle and old age. Here, we used multivariate techniques to investigate the associations between cardiovascular health (diastolic blood pressure, systolic blood pressure, and heart rate) and white matter macrostructure (lesion volume and number) and microstructure (as measured by diffusion-weighted imaging) in the cross-sectional, population-based Cam-CAN cohort (N = 667, aged 18-88). We found that cardiovascular health and age made approximately similar contributions to white matter health and explained up to 56% of variance therein. Lower diastolic blood pressure, higher systolic blood pressure, and higher heart rate were each strongly, and independently, associated with white matter abnormalities on all indices. Body mass and exercise were associated with white matter health, both directly and indirectly via cardiovascular health. These results highlight the importance of cardiovascular risk factors for white matter health across the adult lifespan and suggest that systolic blood pressure, diastolic blood pressure, and heart rate affect white matter health via separate mechanisms.DF, DN, JBR, DP and RAK are supported by the UK Medical Research Council. The Cambridge Centre for Ageing and Neuroscience (Cam-CAN) was supported by the Biotechnology and Biological Sciences Research Council (grant number BB/H008217/1). RAK is supported by the Sir Henry Wellcome Trust (grant number 107392/Z/15/Z) and MRC Programme Grant MC-A060-5PR60. This project has also received funding from the European Union’s Horizon 2020 research and innovation programme (grant agreement number 732592)