The ApoE4 genotype modifies the relationship of long-term glycemic control with cognitive functioning in elderly with type 2 diabetes

Ramit Ravona-Springer*, Anthony Heymann, James Schmeidler, Mary Sano, Rachel Preiss, Keren Koifman, Hadas Hoffman, Jeremy M. Silverman, Michal Schnaider Beeri

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Aim: To assess whether the APOE4 genotype affects the relationship of long-term glycemic control with cognitive function in elderly with type 2 diabetes (T2D). Methods: Participants were cognitively normal and pertained to a Diabetes Registry which provided access to HbA1c levels and other T2D related factors since 1998. Glycemic control was defined as the mean of all HbA1c measurements available (averaging 18 measurements) per subject. Four cognitive domains (episodic memory, semantic categorization, attention/working memory and executive function), based on factor analysis and an overall cognitive score (the sum of the 4 cognitive domains) were the outcome measures. Results: The analysis included 808 subjects; 107 (11.9%) subjects had ≥1ApoE4 allele. In ApoE4 carriers, higher mean HbA1c level was significantly associated with lower scores on all cognitive measures except attention/working memory (p-values ranging from 0.047 to 0.003). In ApoE4 non-carriers, higher mean HbA1c level was significantly associated with lower scores on executive function, but not with other cognitive measures-despite the larger sample size. Compared to non-carriers, there were significantly stronger associations in ApoE4 carriers for overall cognition (p=0.02), semantic categorization (p=0.03) and episodic memory (p=0.02), and the difference for executive function approached statistical significance (p=0.06). Conclusion: In this cross-sectional study of cognitively normal T2D subjects, higher mean HbA1c levels were generally associated with lower cognitive performance in ApoE4 carriers, but not in non-carriers, suggesting that ApoE4 affects the relationship between long-term glycemic control and cognition, so APOE4 carriers may be more vulnerable to the insults of poor glycemic control.

Original languageEnglish
Pages (from-to)1303-1308
Number of pages6
JournalEuropean Neuropsychopharmacology
Volume24
Issue number8
DOIs
StatePublished - Aug 2014

Funding

FundersFunder number
National Institute on AgingR01AG034087, P50 AG05138
American Federation for Aging ResearchNIRG-11-205083
Helen Bader Foundation

    Keywords

    • ApoE
    • Cognition
    • Glycemic control
    • HbA1c
    • Type 2 diabetes

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