Interactive effects of apolipoprotein E4 and diabetes risk on later myelinating white matter regions in neurologically healthy older aged adults

Jessica M. Foley, David H. Salat, Nikki Stricker, Tyler A. Zink, Laura J. Grande, Regina E. McGlinchey, William P. Milberg, Elizabeth C. Leritz

Research output: Contribution to journalArticle

8 Scopus citations


Possession of the apolipoprotein E4 (APOE4) allele and diabetes risk are independently related to reduced white matter (WM) integrity that may contribute to the development of Alzheimer's disease (AD). The purpose of this study is to examine the interactive effects of APOE4 and diabetes risk on later myelinating WM regions among healthy elderly individuals at risk of AD. A sample of 107 healthy elderly (80 APOE4-/27 APOE4+) individuals underwent structural magnetic resonance imaging/diffusion tensor imaging (DTI). Data were prepared using Tract-Based Spatial Statistics, and a priori regions of interest (ROIs) were extracted from T1-based WM parcellations. Regions of interest included later myelinating frontal/temporal/parietal WM regions and control regions measured by fractional anisotropy (FA). There were no APOE group differences in DTI for any ROI. Within the APOE4 group, we found negative relationships between hemoglobin A1c/fasting glucose and APOE4 on FA for all later myelinating WM regions but not for early/middle myelinating control regions. Results also showed APOE4/diabetes risk interactions for WM underlying supramarginal, superior temporal, precuneus, superior parietal, and superior frontal regions. Results suggest interactive effects of APOE4 and diabetes risk on later myelinating WM regions, which supports preclinical detection of AD among this particularly susceptible subgroup.

Original languageEnglish (US)
Pages (from-to)222-235
Number of pages14
JournalAmerican Journal of Alzheimer's Disease and other Dementias
Issue number3
StatePublished - Jan 1 2014
Externally publishedYes



  • Alzheimer's disease
  • APOE4
  • diabetes
  • healthy aging
  • white matter

ASJC Scopus subject areas

  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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