Vascular Risk Factors Tied to Unhealthy Brains, Study from UK Biobank Suggests

Vascular risk factors such as smoking, hypertension, and diabetes were associated with poor brain health. The study by Cox et al., recently published in the European Heart Journal, revealed.

Cerebral small vessel disease, accounting for ∼45% of dementia and ~20% of stroke worldwide, has been linked to vascular risk factors (VRFs) including anthropometric indices, elevated pulse pressure, hypertension, diabetes, and dyslipidemia. However, little is known about which indices on brain magnetic resonance imaging (MRI) best reflect the effects of VRFs. The study by Cox and colleagues addresses the knowledge gap in the relationship between vascular and cerebral aging based on data from UK Biobank, one of the largest general population cohorts that collected information on VRFs and brain imaging among adults in middle and older age.

The study examined brain MRI scans of 9,722 study participants aged between 44 and 79 (mean 61.97±7.48 years). Metrics of brain MRI included total brain volume, grey matter volume, white matter hyperintensity volume, and latent factors of general white matter fractional anisotropy and mean diffusivity. VRFs included smoking pack-years (the number of cigarettes per day divided by 20 and multiplied by the number of years participants reported having smoked for), hypertension, pulse pressure, diabetes, hypercholesterolemia, body mass index, and waist-hip ratio.

The number of VRF was positively associated with more severe brain atrophy (β=-0.061), lower grey matter volume (β=-0.097), and higher white matter hyperintensity (β=0.110). Additionally, the VRF burden demonstrated a stronger association with an unhealthy white matter in older age than younger age (β=0.072 for the main effect and 0.036 for interaction). Specifically, smoking pack-years, hypertension, and diabetes were consistently linked to brain MRI measures, whereas hypercholesterolemia was not uniquely associated with any MRI marker.

Several limitations should be considered. First, the study only included seven variables of neurovascular health. Three of them (hypertension, diabetes, and hypercholesterolemia) were binary and self-reported. Second, due to the cross-sectional design, the study cannot infer the longitudinal relationship of vascular-brain health. Third, the mean age of study participants was 62 years, and the upper limit was 79 years. There may be limited ability to test the effect modification by age on the VRF-brain structure association. Fourth, the study did not involve functional brain imaging or cognitive test. It remains unclear concerning the potential impact of brain structural changes on cognitive outcomes among relatively healthy adults in middle-to-older age. Last, despite significant associations, the effect sizes were modest, and VRFs accounted for less than 2% of the variance in brain MRI metrics.