In 13,680 individuals, risk factors including high waist-to-hip ratio, diabetes, heavy smoking, and APOE ε4/ε4 status were associated with white matter hyperintensity burden and cognitive slowing.
Observational (n=13,680)
Do individual cerebrovascular risk factors affect the spatial distribution of white matter hyperintensities and speed of processing in healthy ageing individuals?
Cerebrovascular risk factors beyond hypertension, particularly visceral adiposity (waist-to-hip ratio), are strongly associated with white matter hyperintensity burden and cognitive slowing in ageing.
Abstract Objectives White matter hyperintensities (WMHs) are considered macroscale markers of cerebrovascular burden and are associated with increased risk of vascular cognitive impairment and dementia. However, the spatial location of WMHs has typically been considered in broad categories of periventricular versus deep white matter. The spatial distribution of WHMs associated with individual cerebrovascular risk factors (CVR), controlling for frequently comorbid risk factors, has not been systematically investigated at the population level in a healthy ageing cohort. Furthermore, there is an inconsistent relationship between total white matter hyperintensity load and cognition, which may be due to the confounding of several simultaneous risk factors in models based on smaller cohorts. Methods We examined trends in individual CVR factors on total WMH burden in 13,680 individuals (aged 45-80) using data from the UK Biobank. We estimated the spatial distribution of white matter hyperintensities associated with each risk factor and their contribution to explaining total WMH load using voxel-wise probit regression and univariate linear regression. Finally, we explored the impact of CVR-related WMHs on speed of processing using regression and mediation analysis. Results Contrary to the assumed dominance of hypertension as the biggest predictor of WMH burden, we show associations with a number of risk factors including diabetes, heavy smoking, APOE ε 4/ ε 4 status and high waist-to-hip ratio of similar, or greater magnitude to hypertension. The spatial distribution of WMHs varied considerably with individual cerebrovascular risk factors. There were independent effects of visceral adiposity, as measured by waist-to-hip ratio, and carriage of the APOE ε 4 allele in terms of the unique spatial distribution of CVR-related WMHs. Importantly, the relationship between total WMH load and speed of processing was mediated by waist-to-hip ratio suggesting cognitive consequences to WMHs associated with excessive visceral fat deposition. Conclusion Waist-to-hip ratio, diabetes, heavy smoking, hypercholesterolemia and homozygous APOE ε 4 status are important risk factors, beyond hypertension, associated with WMH total burden and warrant careful control across ageing. The spatial distribution associated with different risk factors may provide important clues as to the pathogenesis and cognitive consequences of WMHs. High waist-to-hip ratio is a key risk factor associated with slowing in speed of processing. With global obesity levels rising, focused management of visceral adiposity may present a useful strategy for the mitigation of cognitive decline in ageing.
Veldsman et al. (Fri,) conducted a observational in White matter hyperintensities and cognitive decline (n=13,680). Cerebrovascular risk factors (waist-to-hip ratio, diabetes, heavy smoking, APOE ε4/ε4) vs. Absence or lower levels of these risk factors was evaluated on Total white matter hyperintensity (WMH) burden, spatial distribution, and speed of processing. In 13,680 individuals, risk factors including high waist-to-hip ratio, diabetes, heavy smoking, and APOE ε4/ε4 status were associated with white matter hyperintensity burden and cognitive slowing.