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

Abstract

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.

• Authors: Simon R Cox, Stuart J Ritchie, David Alexander Dickie, Alison Pattie, Natalie A Royle, Janie Corley, Benjamin S Aribisala, Sarah E Harris, Maria Valdés Hernández, Alan J Gow, Susana Muñoz Maniega, John M Starr, Mark E Bastin, Joanna M Wardlaw, Ian J Deary
• Journal: Neurobiology of aging (Neurobiol Aging) Vol. 54 Pg. 54-58 (06 2017) ISSN: 1558-1497 [Electronic] United States
• PMID: 28324763 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Apolipoprotein E4
• Blood Glucose

Topics

• Aged
• Aging (genetics, pathology)
• Alleles
• Apolipoprotein E4 (genetics)
• Blood Glucose
• Cohort Studies
• Dementia (etiology)
• Diabetes Complications (blood)
• Disease Progression
• Female
• Forecasting
• Humans
• Magnetic Resonance Imaging
• Male
• Risk Factors
• White Matter (diagnostic imaging, pathology)