APOE Genotypes Associate With Cognitive Performance but Not Cerebral Structure: Diabetes Heart Study MIND

Diabetes Care. 2016 Dec;39(12):2225-2231. doi: 10.2337/dc16-0843. Epub 2016 Oct 4.


Objective: Dementia is a debilitating illness with a disproportionate burden in patients with type 2 diabetes (T2D). Among the contributors, genetic variation at the apolipoprotein E locus (APOE) is posited to convey a strong effect. This study compared and contrasted the association of APOE with cognitive performance and cerebral structure in the setting of T2D.

Research design and methods: European Americans from the Diabetes Heart Study (DHS) MIND (n = 754) and African Americans from the African American (AA)-DHS MIND (n = 517) were examined. The cognitive battery assessed executive function, memory, and global cognition, and brain MRI was performed.

Results: In European Americans and African Americans, the APOE E4 risk haplotype group was associated with poorer performance on the modified Mini-Mental Status Examination (P < 0.017), a measure of global cognition. In contrast to the literature, the APOE E2 haplotype group, which was overrepresented in these participants with T2D, was associated with poorer Rey Auditory Verbal Learning Test performance (P < 0.032). Nominal associations between APOE haplotype groups and MRI-determined cerebral structure were observed.

Conclusions: Compared with APOE E3 carriers, E2 and E4 carriers performed worse in the cognitive domains of memory and global cognition. Identification of genetic contributors remains critical to understanding new pathways to prevent and treat dementia in the setting of T2D.

MeSH terms

  • Aged
  • Apolipoproteins E / genetics*
  • Brain / diagnostic imaging
  • Brain / pathology*
  • Brain / physiopathology
  • Cognition / physiology*
  • Cognition Disorders / complications
  • Cognition Disorders / genetics*
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetes Mellitus, Type 2 / psychology*
  • Female
  • Genetic Association Studies
  • Genotype
  • Heterozygote
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Memory / physiology
  • Middle Aged
  • Neuropsychological Tests


  • Apolipoproteins E