Interaction of APOE e4 and poor glycemic control predicts white matter hyperintensity growth from 73 to 76.
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.
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Department of Psychology, University of Edinburgh, Edinburgh, UK; Scottish Imaging Network, a Platform for Scientific Excellence (SINAPSE) Collaboration, Edinburgh, UK. Electronic address: simon.cox@ed.ac.uk.
Simon R
SR
Cox
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Department of Psychology, University of Edinburgh, Edinburgh, UK.
Stuart J
SJ
Ritchie
Scottish Imaging Network, a Platform for Scientific Excellence (SINAPSE) Collaboration, Edinburgh, UK; Brain Research Imaging Centre, Neuroimaging Sciences, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
David Alexander
DA
Dickie
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Department of Psychology, University of Edinburgh, Edinburgh, UK.
Alison
A
Pattie
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Scottish Imaging Network, a Platform for Scientific Excellence (SINAPSE) Collaboration, Edinburgh, UK; Brain Research Imaging Centre, Neuroimaging Sciences, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK; Department of Computer Science, Lagos State University, Lagos, Nigeria.
Natalie A
NA
Royle
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Department of Psychology, University of Edinburgh, Edinburgh, UK.
Janie
J
Corley
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Scottish Imaging Network, a Platform for Scientific Excellence (SINAPSE) Collaboration, Edinburgh, UK; Brain Research Imaging Centre, Neuroimaging Sciences, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK; Department of Computer Science, Lagos State University, Lagos, Nigeria.
Benjamin S
BS
Aribisala
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Centre for Genomic and Experimental Medicine, MRC Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Sarah E
SE
Harris
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Scottish Imaging Network, a Platform for Scientific Excellence (SINAPSE) Collaboration, Edinburgh, UK; Brain Research Imaging Centre, Neuroimaging Sciences, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
Maria
M
Valdés Hernández
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Department of Psychology, School of Life Sciences, Heriot-Watt University, Edinburgh, UK.
Alan J
AJ
Gow
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Scottish Imaging Network, a Platform for Scientific Excellence (SINAPSE) Collaboration, Edinburgh, UK; Brain Research Imaging Centre, Neuroimaging Sciences, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
Susana
S
Muñoz Maniega
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Alzheimer Scotland Dementia Research Centre, University of Edinburgh, UK.
John M
JM
Starr
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Scottish Imaging Network, a Platform for Scientific Excellence (SINAPSE) Collaboration, Edinburgh, UK; Brain Research Imaging Centre, Neuroimaging Sciences, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
Mark E
ME
Bastin
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Scottish Imaging Network, a Platform for Scientific Excellence (SINAPSE) Collaboration, Edinburgh, UK; Brain Research Imaging Centre, Neuroimaging Sciences, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
Joanna M
JM
Wardlaw
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Department of Psychology, University of Edinburgh, Edinburgh, UK.
Ian J
IJ
Deary
D000368:Aged; D000375:Aging / Q000235:genetics* / Q000473:pathology*; D000483:Alleles; D053327:Apolipoprotein E4 / Q000235:genetics*; D001786:Blood Glucose; D015331:Cohort Studies; D003704:Dementia / Q000209:etiology*; D048909:Diabetes Complications / Q000097:blood; D018450:Disease Progression; D005260:Female; D005544:Forecasting; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D012307:Risk Factors; D066127:White Matter / Q000000981:diagnostic imaging* / Q000473:pathology*
D053327:Apolipoprotein E4; D001786:Blood Glucose
APOE; Aging; Brain MRI; Longitudinal; Vascular risk; White matter