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

Simon R. Cox, Stuart J. Ritchie, David Alexander Dickie, Alison Pattie, Natalie A. Royle, Janie Corley, Benjamin Segun Aribisala, Sarah E. Harris, Maria del Carmen Valdés Hernández, Alan J. Gow, Susana Muñoz Maniega, John M. Starr, Mark E. Bastin, Joanna M. Wardlaw, Ian J. Deary

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)
59 Downloads (Pure)


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.
Original languageEnglish
Pages (from-to)54–58
Number of pages5
JournalNeurobiology of Aging
Early online date27 Feb 2017
Publication statusPublished - Jun 2017


Dive into the research topics of 'Interaction of APOE e4 and poor glycemic control predicts white matter hyperintensity growth from 73 to 76'. Together they form a unique fingerprint.

Cite this