title: Presence of the APOE epsilon4 allele modifies the relationship between type 2 diabetes and cognitive performance: the Maine-Syracuse Study.
abstract: OBJECTIVE
  The primary aim of this study was to determine whether the presence of one or more APOE epsilon4 alleles modifies the association between diabetes (defined by glucose > or =7 mmol/l or treatment) and cognitive function.
  
  
  METHODS
  Diabetic status and APOE genotype interactions were assessed cross-sectionally for 826 community-dwelling, stroke-free, non-demented individuals (526 non-diabetic non-APOE epsilon4 carriers, 174 non-diabetic APOE epsilon4 carriers, 87 diabetic APOE epsilon4 non-carriers, 39 diabetic APOE epsilon4 carriers) ranging in age from 50 to 98 years. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), the similarities subtest from the Wechsler Adult Intelligence Scale, and four composite scores derived from 17 additional neuropsychological tests. Multiple linear regression analyses were employed to relate diabetes and APOE genotype to cognitive performance and to examine the interaction between these two risk factors as they relate to cognitive performance. Multiple cardiovascular disease risk factors were statistically controlled.
  
  
  RESULTS
  With adjustment for age, education, sex, race/ethnicity and APOE genotype, performance level was lower for the diabetic than for the non-diabetic group for the MMSE, the similarities subtest and each of the cognitive composites with the exception of the verbal memory composite. Interactions (p < 0.05) between diabetes and APOE genotype were found for all but the visual-spatial memory/organisation composite. The negative association between diabetes and cognitive performance was of a higher magnitude for individuals who carry one or more APOE epsilon4 alleles. Results were similar with additional adjustment for cardiovascular disease and associated risk factors.
  
  
  CONCLUSIONS
  The presence of one or more APOE epsilon4 alleles modifies the association between diabetes and cognitive function.
authors.affiliation: Department of Psychology, University of Maine, 5742 Little Hall, Orono, ME 04469-5742, USA. gregory.dore@maine.edu
authors.forename: G A
authors.initials: GA
authors.lastname: Dore
authors.forename: M F
authors.initials: MF
authors.lastname: Elias
authors.forename: M A
authors.initials: MA
authors.lastname: Robbins
authors.forename: P K
authors.initials: PK
authors.lastname: Elias
authors.forename: Z
authors.initials: Z
authors.lastname: Nagy
mesh_terms: D000368:Aged; D000483:Alleles; D053327:Apolipoprotein E4 / Q000235:genetics*; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000235:genetics; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000523:psychology*; D005838:Genotype; D006801:Humans; D008019:Life Style; D008128:Logic; D008281:Maine; D008568:Memory / Q000502:physiology*; D008875:Middle Aged; D009483:Neuropsychological Tests; D009518:New York; D018579:Patient Selection; D011581:Psychological Tests; D012016:Reference Values; D012044:Regression Analysis; D014706:Verbal Learning; D014796:Visual Perception
chemical_list: D053327:Apolipoprotein E4
references.citation: Arch Clin Neuropsychol. 1995 Mar;10(2):111-23
references.pmid: 14589733
references.citation: Neurobiol Aging. 2011 Jan;32(1):63-74
references.pmid: 19285755
references.citation: JAMA. 1997 Oct 22-29;278(16):1349-56
references.pmid: 9343467
references.citation: Psychosom Med. 2006 Jul-Aug;68(4):547-54
references.pmid: 16868263
references.citation: Diabetes Care. 2009 Jan;32 Suppl 1:S13-61
references.pmid: 19118286
references.citation: Neurology. 1997 Nov;49(5):1306-11
references.pmid: 9371913
references.citation: Arch Neurol. 1997 Sep;54(9):1110-4
references.pmid: 9311354
references.citation: Eur Neurol. 2007;57(2):70-4
references.pmid: 17179707
references.citation: J Geriatr Psychiatry Neurol. 2005 Dec;18(4):245-9
references.pmid: 16306248
references.citation: Brain. 2007 Nov;130(Pt 11):2837-44
references.pmid: 17928318
references.citation: Exp Aging Res. 2008 Apr-Jun;34(2):152-61
references.pmid: 18351501
references.citation: Eur J Pharmacol. 2004 Apr 19;490(1-3):187-97
references.pmid: 15094085
references.citation: Neurology. 2000 Jun 13;54(11):2082-8
references.pmid: 10851367
references.citation: Am J Kidney Dis. 2004 Jan;43(1):112-9
references.pmid: 14712434
references.citation: Soc Psychiatry Psychiatr Epidemiol. 2005 Jul;40(7):557-63
references.pmid: 16021346
references.citation: JAMA. 1999 Jul 7;282(1):40-6
references.pmid: 10404910
references.citation: J Lipid Res. 1990 Mar;31(3):545-8
references.pmid: 2341813
references.citation: Neuroscience. 1995 Dec;69(3):757-61
references.pmid: 8596645
references.citation: J Gerontol B Psychol Sci Soc Sci. 2005 Jan;60(1):P41-8
references.pmid: 15643038
references.citation: Neurology. 2003 Apr 8;60(7):1089-93
references.pmid: 12682311
references.citation: Diabetes Care. 1997 Mar;20(3):438-45
references.pmid: 9051402
references.citation: Ann Intern Med. 1999 Mar 16;130(6):461-70
references.pmid: 10075613
references.citation: J Neurol Neurosurg Psychiatry. 2002 Jun;72(6):794-7
references.pmid: 12023428
references.citation: Exp Gerontol. 2003 Sep;38(9):941-6
references.pmid: 12954480
references.citation: Am J Pathol. 2003 Jan;162(1):313-9
references.pmid: 12507914
references.citation: J Am Geriatr Soc. 1998 Dec;46(12):1493-8
references.pmid: 9848808
references.citation: Psychol Aging. 2004 Dec;19(4):592-600
references.pmid: 15584785
references.citation: Diabetologia. 2005 Dec;48(12):2460-9
references.pmid: 16283246
references.citation: Arch Neurol. 2008 Jan;65(1):89-93
references.pmid: 18195144
references.citation: Stroke. 2004 Feb;35(2):404-9
references.pmid: 14726556
references.citation: Neurology. 2004 Sep 14;63(5):816-21
references.pmid: 15365129
references.citation: Neurology. 1984 Jul;34(7):939-44
references.pmid: 6610841
references.citation: Neurobiol Aging. 2010 Oct;31(10):1831-3
references.pmid: 19004527
references.citation: Neurosci Lett. 2002 May 10;324(1):74-6
references.pmid: 11983298
references.citation: Diabetes Care. 1997 Sep;20(9):1388-95
references.pmid: 9283785
references.citation: Neurobiol Aging. 2005 Dec;26 Suppl 1:21-5
references.pmid: 16213627
references.citation: Diabetes. 2002 Apr;51(4):1256-62
references.pmid: 11916953
references.citation: Neurosci Lett. 1997 May 2;226(3):155-8
references.pmid: 9175590
references.citation: Neurosci Lett. 2008 Jan 3;430(1):64-9
references.pmid: 18023533
references.citation: J Am Geriatr Soc. 2005 Mar;53(3):381-8
references.pmid: 15743278
references.citation: Neurobiol Aging. 2000 Mar-Apr;21(2):245-55
references.pmid: 10867209
references.citation: J Clin Exp Neuropsychol. 2004 Nov;26(8):1044-80
references.pmid: 15590460
references.citation: Arch Neurol. 2000 Jun;57(6):808-13
references.pmid: 10867777
references.citation: Neuropathol Appl Neurobiol. 2009 Feb;35(1):60-8
references.pmid: 18346114