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Diabetologia

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01-12-2009 | Article

Presence of the APOE ε4 allele modifies the relationship between type 2 diabetes and cognitive performance: the Maine–Syracuse Study

Authors: G. A. Dore, M. F. Elias, M. A. Robbins, P. K. Elias, Z. Nagy

Published in: Diabetologia | Issue 12/2009

Abstract

Aims/hypothesis

The primary aim of this study was to determine whether the presence of one or more APOE ε4 alleles modifies the association between diabetes (defined by glucose ≥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 ε4 carriers, 174 non-diabetic APOE ε4 carriers, 87 diabetic APOE ε4 non-carriers, 39 diabetic APOE ε4 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 ε4 alleles. Results were similar with additional adjustment for cardiovascular disease and associated risk factors.

Conclusions/interpretation

The presence of one or more APOE ε4 alleles modifies the association between diabetes and cognitive function.

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Elias PK, Elias MF, D'Agostino RB et al (1997) NIDDM and blood pressure as risk factors for poor cognitive performance. The Framingham Study. Diabetes Care 20:1388–1395CrossRefPubMed

Awad N, Gagnon M, Messier C (2004) The relationship between impaired glucose tolerance, type 2 diabetes, and cognitive function. J Clin Exp Neuropsychol 26:1044–1080CrossRefPubMed

Cukierman T, Gerstein HC, Williamson JD (2005) Cognitive decline and dementia in diabetes—systematic overview of prospective observational studies. Diabetologia 48:2460–2469CrossRefPubMed

Ryan CM (2005) Diabetes, aging, and cognitive decline. Neurobiol Aging 26:S21–S25CrossRef

Sima AA, Kamiya H, Li ZG (2004) Insulin, C-peptide, hyperglycemia, and central nervous system complications in diabetes. Eur J Pharmacol 490:187–197CrossRefPubMed

Galanina N, Surampudi V, Ciltea D, Singh SP, Perlmuter LC (2008) Blood glucose levels before and after cognitive testing in diabetes mellitus. Exp Aging Res 34:152–161CrossRefPubMed

Farrer LA, Cupples LA, Haines JL et al (1997) Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. J Am Med Assoc 278:1349–1356CrossRef

Small BJ, Rosnick CB, Fratiglioni L et al (2004) Apolipoprotein E and cognitive performance: a meta-analysis. Psychol Aging 19:592–600CrossRefPubMed

O'Hara R, Yesavage JA, Kraemer HC, Mauricio M, Friedman LF, Murphy GM Jr (1998) The APOE epsilon4 allele is associated with decline on delayed recall performance in community-dwelling older adults. J Am Geriatr Soc 46:1493–1498PubMed

10.

Yaffe K, Cauley J, Sands L, Browner W (1997) Apolipoprotein E phenotype and cognitive decline in a prospective study of elderly community women. Arch Neurol 54:1110–1114PubMed

11.

Bunce D, Fratiglioni L, Small BJ, Winblad B, Bäckman L (2004) APOE and cognitive decline in preclinical Alzheimer disease and non-demented aging. Neurology 63:816–821PubMed

12.

Pendleton N, Payton A, van den Boogerd EH et al (2002) Apolipoprotein E genotype does not predict decline in intelligence in healthy older adults. Neurosci Lett 324:74–76CrossRefPubMed

13.

Small BJ, Graves AB, McEvoy CL, Crawford FC, Mullan M, Mortimer JA (2000) Is APOE-ε4 a risk factor for cognitive impairment in normal aging? Neurology 54:2082–2088PubMed

14.

Winnock M, Letenneur L, Jacqmin-Gadda H, Dallongeville J, Amouyel P, Dartigues JF (2002) Longitudinal analysis of the effect of apolipoprotein E epsilon4 and education on cognitive performance in elderly subjects: the PAQUID study. J Neurol Neurosurg Psychiatry 72:794–797CrossRefPubMed

15.

Zhao JH, Brunner EJ, Kumari M et al (2005) APOE polymorphism, socioeconomic status and cognitive function in mid-life—the Whitehall II longitudinal study. Soc Psychiatry Psychiatr Epidemiol 40:557–563CrossRefPubMed

16.

Haan MN, Shemanski L, Jagust WJ et al (1999) The role of APOE epsilon4 in modulating effects of other risk factors for cognitive decline in elderly persons. J Am Med Assoc 282:40–46CrossRef

17.

Irie F, Fitzpatrick AL, Lopez OL et al (2008) Enhanced risk for Alzheimer disease in persons with type 2 diabetes and APOE epsilon4: the Cardiovascular Health Study Cognition Study. Arch Neurol 65:89–93CrossRefPubMed

18.

Peila R, Rodriguez BL, Launer LJ (2002) Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: the Honolulu-Asia Aging Study. Diabetes 51:1256–1262CrossRefPubMed

19.

Elias MF, Robbins MA, Budge MM et al (2006) Homocysteine, folate, and vitamins B6 and B12 blood levels in relation to cognitive performance: the Maine-Syracuse study. Psychosom Med 68:547–554CrossRefPubMed

20.

Liu F, Pardo LM, Schuur M et al (2008) The apolipoprotein E gene and its age-specific effects on cognitive function. Neurobiol Aging. doi:10.1016/j.neurobiolaging.2008.09.015

21.

Sager MA, Hermann B, La Rue A (2005) Middle-aged children of persons with Alzheimer’s disease: APOE genotypes and cognitive function in the Wisconsin registry for Alzheimer’s prevention. J Geriatr Psychiatry Neurol 18:245–249CrossRefPubMed

22.

McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlam EM (1984) Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 34:939–944PubMed

23.

Radloff LS (1977) The CES-D scale: a self-report depression scale for research in the general population. Appl Psych Meas 1:385–401CrossRef

24.

American Diabetes Association (2009) Standards of medical care in diabetes—2009. Diabetes Care 32:S13–S61CrossRef

25.

Hixson JE, Vernier DT (1990) Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res 31:545–548PubMed

26.

Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 130:461–470PubMed

27.

Rule AD, Gusak HM, Pond GR et al (2004) Measured and estimated GFR in healthy potential kidney donors. Am J Kidney Dis 43:112–119CrossRefPubMed

28.

Elias MF, Sullivan LM, D'Agostino RB et al (2004) Framingham stroke risk profile and lowered cognitive performance. Stroke 35:404–409CrossRefPubMed

29.

Schafer JH, Glass TA, Bolla KI, Mintz M, Jedlicka AE, Schwartz BS (2005) Homocysteine and cognitive function in a population-based study of older adults. J Am Geriatr Soc 53:381–388CrossRefPubMed

30.

Bunce D, Kivipelto M, Wahlin A (2005) Apolipoprotein E, B vitamins, and cognitive function in older adults. J Gerontol B Psychol Sci Soc Sci 60:P41–P48PubMed

31.

Wisdom NM, Callahan JL, Hawkins KA (2009) The effects of apolipoprotein E on non-impaired cognitive functioning: a meta-analysis. Neurobiol Aging. doi:10.1016/j.neurobiolaging.2009.02.003 PubMed

32.

Strachan MW, Deary IJ, Ewing FM, Frier BM (1997) Is type II diabetes associated with an increased risk of cognitive dysfunction? A critical review of published studies. Diabetes Care 20:438–445CrossRefPubMed

33.

Elias MF, Robbins MA, Budge MM (2008) Homocysteine and cognitive performance: modification by the ApoE genotype. Neurosci Lett 430:64–69CrossRefPubMed

34.

Messier C (2003) Diabetes, Alzheimer's disease and apolipoprotein genotype. Exp Gerontol 38:941–946CrossRefPubMed

35.

Pike KE, Savage G, Villemagne VL et al (2007) Beta-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer's disease. Brain 130:2837–2844CrossRefPubMed

36.

Cook DG, Leverenz JB, McMillan PJ et al (2003) Reduced hippocampal insulin-degrading enzyme in late-onset Alzheimer's disease is associated with the apolipoprotein E-epsilon4 allele. Am J Pathol 162:313–319PubMed

37.

Heitner J, Dickson D (1997) Diabetics do not have increased Alzheimer-type pathology compared with age-matched control subjects: a retrospective postmortem immunocytochemical and histofluorescent study. Neurology 49:1306–1311PubMed

38.

Alafuzoff I, Aho L, Helisalmi S, Mannermaa A, Soininen H (2009) β-Amyloid deposition in brains of subjects with diabetes. Neuropathol Appl Neurobiol 35:60–68CrossRefPubMed

39.

van Harten B, Oosterman JM, van Loon BP, Scheltens P, Weinstein HC (2007) Brain lesions on MRI in elderly patients with Type 2 diabetes mellitus. Eur Neurol 57:70–74CrossRefPubMed

40.

Nagy Z, Esiri MM, Jobst KA, Johnston C et al (1995) Influence of the apolipoprotein E genotype on amyloid deposition and neurofibrillary tangle formation in Alzheimer's disease. Neuroscience 69:757–761CrossRefPubMed

41.

Horsburgh K, McCarron MO, White F, Nicoll JA (2000) The role of apolipoprotein E in Alzheimer's disease, acute brain injury and cerebrovascular disease: evidence of common mechanisms and utility of animal models. Neurobiol Aging 21:245–255CrossRefPubMed

42.

Li YM, Dickson DW (1997) Enhanced binding of advanced glycation endproducts (AGE) by the ApoE4 isoform links the mechanism of plaque deposition in Alzheimer's disease. Neuroscience Letters 226:155–158CrossRefPubMed

43.

Kawas CH, Corrada MM, Brookmeyer R et al (2003) Visual memory predicts Alzheimer’s disease more than a decade before diagnosis. Neurology 60:1089–1093CrossRefPubMed

44.

Zonderman AB, Glambra LM, Arenberg D, Renick SM, Costa PT Jr (1993) Changes in immediate visual memory predict cognitive impairment. Arch Clin Neuropsych 10:111–123

45.

Elias MF, Beiser A, Wolf PA, Au R, White RF, D'Agostino RB (2000) The preclinical phase of Alzheimer disease: a 22-year prospective study of the Framingham cohort. Arch Neurol 57:808–813CrossRefPubMed

Title: Presence of the APOE ε4 allele modifies the relationship between type 2 diabetes and cognitive performance: the Maine–Syracuse Study
Authors: G. A. Dore
M. F. Elias
M. A. Robbins
P. K. Elias
Z. Nagy
Publication date: 01-12-2009
Publisher: Springer-Verlag
Published in: Diabetologia / Issue 12/2009
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-009-1497-2

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Abstract

Aims/hypothesis

Methods

Results

Conclusions/interpretation

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