title: Long-term Variability in Glycemic Control Is Associated With White Matter Hyperintensities in APOE4 Genotype Carriers With Type 2 Diabetes.
abstract: We assessed whether the apolipoprotein ε4 (APOE4) genotype affects the relationship of variability in long-term glycemic control (measured by HbA1c SD of multiple measurements) with white matter hyperintensities (WMHs) in elderly patients with type 2 diabetes (T2D).
  
  
  
  WMH volume was generated from structural T1 and fluid-attenuated inversion recovery MRI in each subject. The analysis included 124 subjects; 27 (21.8%) had one or more APOE4 alleles.
  
  
  
  HbA1c variability was associated with significantly higher WMH in APOE4 carriers (r = 0.47, P = 0.03), controlling for age, sex, mean HbA1c, number of follow-up years, and a composite of cardiovascular risk factors, but not in noncarriers (r = -0.04, P = 0.71; P for interaction = 0.050).
  
  
  
  The results suggest that the APOE4 genotype affects the relationship of long-term glycemic control with WMH load so that APOE4 carriers may be more vulnerable to the insults of poor control.
authors.affiliation: Department of Diagnostic Imaging, Sheba Medical Center, Tel HaShomer, Israel Josef Sagol Neuroscience Center, Sheba Medical Center, Tel HaShomer, Israel abigail.livnyezer@gmail.com.
authors.forename: Abigail
authors.identifier: 0000-0003-2216-7357
authors.initials: A
authors.lastname: Livny
authors.affiliation: Josef Sagol Neuroscience Center, Sheba Medical Center, Tel HaShomer, Israel Memory Clinic, Sheba Medical Center, Tel HaShomer, Israel.
authors.forename: Ramit
authors.identifier: 0000-0002-6440-3322
authors.initials: R
authors.lastname: Ravona-Springer
authors.affiliation: Maccabi Healthcare Services, Tel Aviv, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Anthony
authors.identifier: 0000-0003-2353-9933
authors.initials: A
authors.lastname: Heymann
authors.affiliation: Maccabi Healthcare Services, Tel Aviv, Israel.
authors.forename: Rachel
authors.initials: R
authors.lastname: Priess
authors.affiliation: Department of Diagnostic Imaging, Sheba Medical Center, Tel HaShomer, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Tammar
authors.initials: T
authors.lastname: Kushnir
authors.affiliation: Department of Diagnostic Imaging, Sheba Medical Center, Tel HaShomer, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Galia
authors.initials: G
authors.lastname: Tsarfaty
authors.affiliation: Department of Diagnostic Imaging, Sheba Medical Center, Tel HaShomer, Israel.
authors.forename: Leeron
authors.initials: L
authors.lastname: Rabinov
authors.affiliation: Department of Diagnostic Imaging, Sheba Medical Center, Tel HaShomer, Israel.
authors.forename: Reut
authors.initials: R
authors.lastname: Moran
authors.affiliation: Josef Sagol Neuroscience Center, Sheba Medical Center, Tel HaShomer, Israel.
authors.forename: Hadass
authors.initials: H
authors.lastname: Hoffman
authors.affiliation: Josef Sagol Neuroscience Center, Sheba Medical Center, Tel HaShomer, Israel School of Psychology, Interdisciplinary Center Herzliya, Herzliya, Israel.
authors.forename: Itzik
authors.initials: I
authors.lastname: Cooper
authors.affiliation: Josef Sagol Neuroscience Center, Sheba Medical Center, Tel HaShomer, Israel.
authors.forename: Lior
authors.initials: L
authors.lastname: Greenbaum
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY James J. Peters Veterans Affairs Medical Center, Bronx, NY.
authors.forename: Jeremy
authors.identifier: 0000-0001-5899-128X
authors.initials: J
authors.lastname: Silverman
authors.affiliation: School of Psychology, Interdisciplinary Center Herzliya, Herzliya, Israel.
authors.forename: Mary
authors.initials: M
authors.lastname: Sano
authors.affiliation: William S. Middleton Memorial Veterans Hospital, Madison, WI Wisconsin Alzheimer's Disease Research Center, Madison, WI.
authors.forename: Sterling C
authors.identifier: 0000-0002-8501-545X
authors.initials: SC
authors.lastname: Johnson
authors.affiliation: William S. Middleton Memorial Veterans Hospital, Madison, WI Wisconsin Alzheimer's Disease Research Center, Madison, WI.
authors.forename: Barbara B
authors.identifier: 0000-0002-0580-9875
authors.initials: BB
authors.lastname: Bendlin
authors.affiliation: Josef Sagol Neuroscience Center, Sheba Medical Center, Tel HaShomer, Israel School of Psychology, Interdisciplinary Center Herzliya, Herzliya, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Schnaider Beeri
mesh_terms: D000368:Aged; D000483:Alleles; D053327:Apolipoprotein E4 / Q000235:genetics*; D001786:Blood Glucose / Q000378:metabolism*; D002318:Cardiovascular Diseases; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006579:Heterozygote; D006801:Humans; D056784:Leukoencephalopathies / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size; D012307:Risk Factors; D066127:White Matter / Q000000981:diagnostic imaging* / Q000473:pathology
chemical_list: D053327:Apolipoprotein E4; D001786:Blood Glucose; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human