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

Neurobiol Aging. 2017 Jun:54:54-58. doi: 10.1016/j.neurobiolaging.2017.02.014. Epub 2017 Feb 27.

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.

Keywords: APOE; Aging; Brain MRI; Longitudinal; Vascular risk; White matter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging / genetics*
  • Aging / 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*
  • White Matter / pathology*

Substances

  • Apolipoprotein E4
  • Blood Glucose