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

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.
Original languageEnglish
Pages (from-to)54–58
Number of pages5
JournalNeurobiology of Aging
Volume54
Early online date27 Feb 2017
DOIs
StatePublished - Jun 2017

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Apolipoprotein E4
Apolipoproteins E
White Matter
risk factor
risk
Blood Vessels
blood
age
diabetes
brain
allele
interaction
Alleles
Blood Pressure
Brain
chronic illness
control
hypertension
hemoglobin
smoking

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Cox, S. R., Ritchie, S. J., Dickie, D. A., Pattie, A., Royle, N. A., Corley, J., ... Deary, I. J. (2017). Interaction of APOE e4 and poor glycemic control predicts white matter hyperintensity growth from 73 to 76. Neurobiology of Aging, 54, 54–58. DOI: 10.1016/j.neurobiolaging.2017.02.014

Cox, Simon R.; Ritchie, Stuart J.; Dickie, David Alexander; Pattie, Alison; Royle, Natalie A.; Corley, Janie; Aribisala, Benjamin Segun; Harris, Sarah E.; del Carmen Valdés Hernández, Maria; Gow, Alan J.; Muñoz Maniega, Susana; Starr, John M.; Bastin, Mark E.; Wardlaw, Joanna M.; Deary, Ian J. / Interaction of APOE e4 and poor glycemic control predicts white matter hyperintensity growth from 73 to 76.

In: Neurobiology of Aging, Vol. 54, 06.2017, p. 54–58.

Research output: Contribution to journalArticle

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title = "Interaction of APOE e4 and poor glycemic control predicts white matter hyperintensity growth from 73 to 76",
author = "Cox, {Simon R.} and Ritchie, {Stuart J.} and Dickie, {David Alexander} and Alison Pattie and Royle, {Natalie A.} and Janie Corley and Aribisala, {Benjamin Segun} and Harris, {Sarah E.} and {del Carmen Valdés Hernández}, Maria and Gow, {Alan J.} and {Muñoz Maniega}, Susana and Starr, {John M.} and Bastin, {Mark E.} and Wardlaw, {Joanna M.} and Deary, {Ian J.}",
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Cox, SR, Ritchie, SJ, Dickie, DA, Pattie, A, Royle, NA, Corley, J, Aribisala, BS, Harris, SE, del Carmen Valdés Hernández, M, Gow, AJ, Muñoz Maniega, S, Starr, JM, Bastin, ME, Wardlaw, JM & Deary, IJ 2017, 'Interaction of APOE e4 and poor glycemic control predicts white matter hyperintensity growth from 73 to 76' Neurobiology of Aging, vol 54, pp. 54–58. DOI: 10.1016/j.neurobiolaging.2017.02.014

Interaction of APOE e4 and poor glycemic control predicts white matter hyperintensity growth from 73 to 76. / Cox, Simon R.; Ritchie, Stuart J.; Dickie, David Alexander; Pattie, Alison; Royle, Natalie A.; Corley, Janie; Aribisala, Benjamin Segun; Harris, Sarah E.; del Carmen Valdés Hernández, Maria; Gow, Alan J.; Muñoz Maniega, Susana; Starr, John M.; Bastin, Mark E.; Wardlaw, Joanna M.; Deary, Ian J.

In: Neurobiology of Aging, Vol. 54, 06.2017, p. 54–58.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Interaction of APOE e4 and poor glycemic control predicts white matter hyperintensity growth from 73 to 76

AU - Cox,Simon R.

AU - Ritchie,Stuart J.

AU - Dickie,David Alexander

AU - Pattie,Alison

AU - Royle,Natalie A.

AU - Corley,Janie

AU - Aribisala,Benjamin Segun

AU - Harris,Sarah E.

AU - del Carmen Valdés Hernández,Maria

AU - Gow,Alan J.

AU - Muñoz Maniega,Susana

AU - Starr,John M.

AU - Bastin,Mark E.

AU - Wardlaw,Joanna M.

AU - Deary,Ian J.

PY - 2017/6

Y1 - 2017/6

N2 - 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.

AB - 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.

U2 - 10.1016/j.neurobiolaging.2017.02.014

DO - 10.1016/j.neurobiolaging.2017.02.014

M3 - Article

VL - 54

SP - 54

EP - 58

JO - Neurobiology of Aging

T2 - Neurobiology of Aging

JF - Neurobiology of Aging

SN - 0197-4580

ER -

Cox SR, Ritchie SJ, Dickie DA, Pattie A, Royle NA, Corley J et al. Interaction of APOE e4 and poor glycemic control predicts white matter hyperintensity growth from 73 to 76. Neurobiology of Aging. 2017 Jun;54:54–58. Available from, DOI: 10.1016/j.neurobiolaging.2017.02.014