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Spatial distribution and cognitive impact of cerebrovascular risk-related white matter hyperintensities
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Veldsman, Michele, Kindalova, Petya, Husain, Masud, Kosmidis, Ioannis and Nichols, Thomas E. (2020) Spatial distribution and cognitive impact of cerebrovascular risk-related white matter hyperintensities. NeuroImage, 28 . 102405. doi:10.1016/j.nicl.2020.102405 ISSN 1053-8119.
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Official URL: https://doi.org/10.1016/j.nicl.2020.102405
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 4/ 4 status and high waist- to-hip ratio of similar, or greater magnitude to hypertension. The spatial distribution of WMHs varied con- siderably with individual cerebrovascular risk factors. There were independent effects of visceral adiposity, as measured by waist-to-hip ratio, and carriage of the APOE 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 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.
Item Type: | Journal Article | |||||||||||||||||||||||||||
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Subjects: | H Social Sciences > HA Statistics Q Science > QP Physiology R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Statistics Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences > Statistics and Epidemiology |
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Library of Congress Subject Headings (LCSH): | White matter, Cardiovascular system -- Diseases, Cardiovascular system -- Diseases -- Diagnosis, Apolipoprotein E | |||||||||||||||||||||||||||
Journal or Publication Title: | NeuroImage | |||||||||||||||||||||||||||
Publisher: | Elsevier | |||||||||||||||||||||||||||
ISSN: | 1053-8119 | |||||||||||||||||||||||||||
Official Date: | 1 September 2020 | |||||||||||||||||||||||||||
Dates: |
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Volume: | 28 | |||||||||||||||||||||||||||
Article Number: | 102405 | |||||||||||||||||||||||||||
DOI: | 10.1016/j.nicl.2020.102405 | |||||||||||||||||||||||||||
Status: | Peer Reviewed | |||||||||||||||||||||||||||
Publication Status: | Published | |||||||||||||||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||||||||||||||
Copyright Holders: | Michele Veldsman, Petya Kindalova, Masud Husain, Ioannis Kosmidis, Thomas E. Nichols | |||||||||||||||||||||||||||
Date of first compliant deposit: | 2 December 2020 | |||||||||||||||||||||||||||
Date of first compliant Open Access: | 2 December 2020 | |||||||||||||||||||||||||||
RIOXX Funder/Project Grant: |
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