title: The ApoE4 genotype modifies the relationship of long-term glycemic control with cognitive functioning in elderly with type 2 diabetes.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Memory clinic, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. Electronic address: ramit.ravona@sheba.health.gov.il.
authors.forename: Ramit
authors.initials: R
authors.lastname: Ravona-Springer
authors.affiliation: Department of Family Medicine, University of Tel Aviv, Israel.
authors.forename: Anthony
authors.initials: A
authors.lastname: Heymann
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, NY, USA.
authors.forename: James
authors.initials: J
authors.lastname: Schmeidler
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, NY, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Sano
authors.affiliation: Maccabi Health Services, Israel.
authors.forename: Rachel
authors.initials: R
authors.lastname: Preiss
authors.affiliation: Memory clinic, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
authors.forename: Keren
authors.initials: K
authors.lastname: Koifman
authors.affiliation: Maccabi Health Services, Israel.
authors.forename: Hadas
authors.initials: H
authors.lastname: Hoffman
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, NY, USA.
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Silverman
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, NY, USA; Josef Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
authors.forename: Michal Schnaider
authors.initials: MS
authors.lastname: Beeri
mesh_terms: D000368:Aged; D000375:Aging / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D001288:Attention / Q000502:physiology; D001786:Blood Glucose; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics*; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology; D008875:Middle Aged; D009483:Neuropsychological Tests; D021641:Recognition, Psychology / Q000502:physiology
chemical_list: D053327:Apolipoprotein E4; D001786:Blood Glucose; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human
keywords: ApoE; Cognition; Glycemic control; HbA1c; Type 2 diabetes