APOE e 4 status and poor glycaemic control predict white matter hyperintensity growth from 73 - 76 years

APOE e4 status and poor glycaemic control predict white matter hyperintensity growth from 73-76 years' Neurobiology of Aging. General rights Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer content complies with UK legislation. If you believe that the public display of this file breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Accepted Manuscript APOE e4 status and poor glycaemic control predict white matter hyperintensity growth from 73-76 years This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Abstract We examined whether APOE status interacts with vascular risk factors (VRFs) to predict progression of white matter hyperintensities (WMHs) on brain MRI scans over a specific period of life in older age when 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 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 haemoglobin 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 non-significant (β interaction < 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 glycaemic control. The interaction effect …