Interaction of APOE e4 and poor glycemic control predicts white matter hyperintensity growth from 73 to 76

Cox, S. R. et al. (2017) Interaction of APOE e4 and poor glycemic control predicts white matter hyperintensity growth from 73 to 76. Neurobiology of Aging, 54, pp. 54-58. (doi: 10.1016/j.neurobiolaging.2017.02.014) (PMID:28324763) (PMCID:PMC5407886)

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We examined whether apolipoprotein E (APOE) status interacts with vascular risk factors (VRFs) to predict the progression of white matter hyperintensities (WMHs) on brain MRI scans over a specific period of life in older age when the risk of dementia increases. At age 73 years, baseline VRFs were assessed via self-reported history of diabetes, hypertension, smoking, and hypercholesterolemia, and via objective measures of blood HbA1c, body mass index, diastolic and systolic blood pressure, and blood high-density lipoprotein to total cholesterol (HDL) ratio. APOE e4 allele was coded as either present or absent. WMH progression was measured on MRI over 3 years in 434 older adults, in a same-year-of-birth cohort. APOE e4 carriers with either a self-reported diagnosis of diabetes (β = 0.160, p = 0.002) or higher glycated hemoglobin levels (β = 0.114, p = 0.014) exhibited greater WMH progression, and the former survived correction for multiple testing. All other APOE-VRF interactions were nonsignificant (βinteraction < 0.056, p > 0.228). The results suggest that carrying the APOE “risk” e4 allele increases the risk of greater age-related WMH progression over the early part of the eighth decade of life, when combined with poorer glycemic control. The interaction effect was robust to co-occurring VRFs, suggesting a possible target for mitigating brain and cognitive aging at this age.

Item Type:Articles
Additional Information:This work was supported by a Research into Ageing programme grant (I. J. D. and J. M. S.) and the Age UK-funded Disconnected Mind project (I. J. D., J. M. S., and J. M. W.), with additional funding from the UK Medical Research Council (I. J. D., J. M. S., J. M. W., and M. E. B.) under grant numbers G0701120, G1001245, and MR/M013111/1. J. M. W. is supported by the Scottish Funding Council through the SINAPSE Collaboration ( M. V. H. is supported by the Row Fogo Charitable Trust (grant number: BRO-D.FID3668413). The work was undertaken within The University of Edinburgh Centre for Clinical Brain Sciences and Centre for Cognitive Aging and Cognitive Epidemiology (, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1). Funding from the UK Biotechnology and Biological Sciences Research Council and the Medical Research Council are gratefully acknowledged.
Glasgow Author(s) Enlighten ID:Dickie, Dr David Alexander
Authors: Cox, S. R., Ritchie, S. J., Dickie, D. A., Pattie, A., Royle, N. A., Corley, J., Aribisala, B. S., Harris, S. E., Valdés Hernández, M., Gow, A. J., Muñoz Maniega, S., Starr, J. M., Bastin, M. E., Wardlaw, J. M., and Deary, I. J.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Neurobiology of Aging
ISSN (Online):1558-1497
Published Online:27 February 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Neurobiology of Aging 54:54-58
Publisher Policy:Reproduced under a Creative Commons License

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