Diabetes mellitus in patients with Alzheimer’s disease: clinical description and correlation with the APOE genotype in a sample population from the province of Antioquia, Colombia
Abstract
Introduction. Alzheimer’s disease is a multifactorial disease affecting approximately twenty million people worldwide. Numerous variables are associated with increased risk of developing this severe neurological disorder. Among the risk factors, diabetes mellitus, and the ε4 isoform of the APOE gene have been amply demonstrated as increasing the risk of developing this disease.
Objective. To determine if a correlation exists between APOE genotype, diabetes mellitus and Alzheimer’s disease.
Materials and methods. Clinical studies were carried out by surveying the clinical histories in a group of patients in the province of Antioquia, Colombia. Forty-three Alzheimer’s patients were compared with 43 control subjects, paired by age and gender. Commercially available methods were used to determine whether the patients had diabetes, and restriction enzyme-based genotyping was used to determine the APOE genotypes.
Results. The most common non-neurological comorbidities were: arterial hypertension, acute myocardial infarction, chronic obstructive pulmonary disease and hypothyroidism. From the many variables investigated, two were conclusive: (1) the presence of Alzheimer’s disease was higher in patients with diabetes mellitus, and (2) no correlation between late-onset sporadic Alzheimer’s disease and APOE was found in the target population.
Conclusions. To detect any association with the APOE genotype, a study involving much a larger population samples must be undertaken.
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Barnes DE, Yaffe K. The projected effect of risk factor reduction on Alzheimer’s disease prevalence. Lancet Neurol. 2011;10:819-28. doi: http://dx.doi.org/10.1016/S1474-4422(11)70072-2
Wimo A, Winblad B, Jonsson L. The worldwide societal costs of dementia: Estimates for 2009. Alzheimers Dement. 2010;6:98-103. doi: http://dx.doi.org/10.1016/j.jalz.2010.01.010
WHO. Atlas: Country resources for neurological disorders. World Health Organization and World Federation of Neurology. Geneva: WHO; 2004. p. 52.
Selkoe DJ. Alzheimer’s disease: Genes, proteins, and therapy. Physiol Rev. 2001;81:741-66. PMid:11274343
Martin JB. Molecular basis of the neurodegenerative disorders. N Engl J Med. 1999;340:1970-80. doi: http://dx.doi.org/10.1056/NEJM199906243402507
Huang C, Wahlund LO, Svensson L, Winblad B, Julin P. Cingulate cortex hypoperfusion predicts Alzheimer’s disease in mild cognitive impairment. BMC Neurol. 2002; 2:9. doi: http://dx.doi.org/10.1186/1471-2377-2-9
Dede DS, Yavuz B, Yavuz BB, Cankurtaran M, Halil M, Ulger Z, et al. Assessment of endothelial function in Alzheimer’s disease: Is Alzheimer’s disease a vascular disease? J Am Geriatr Soc. 2007;55:1613-7. doi: http://dx.doi.org/10.1111/j.1532-5415.2007.01378.x
Dodart JC, Marr RA, Koistinaho M, Gregersen BM, Malkani S, Verma IM, et al. Gene delivery of human apolipoprotein E alters brain A beta burden in a mouse model of Alzheimer’s disease. Proc Natl Acad Sci U S A. 2005;102:1211-6. doi: http://dx.doi.org/10.1073/pnas.0409072102
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. Fourth edition. Washington, DC: APA; 2000. p. 157.
Dickson DW. Neuropathological diagnosis of Alzheimer’s disease: A perspective from longitudinal clinicopathological studies. Neurobiol Aging. 1997;18(Suppl.):S21-6. doi: http://dx.doi.org/10.1016/S0197-4580(97)00065-1
Fagan AM, Holtzman DM. Cerebrospinal fluid biomarkers of Alzheimer’s disease. Biomark Med. 2010;4:51-63. doi: http://dx.doi.org/10.2217/bmm.09.83
Alzheimer’s Association, Thies W, Bleiler L. Alzheimer’s disease facts and figures. Alzheimers Dement. 2011;7:208-44. doi: http://dx.doi.org/10.1016/j.jalz.2011.02.004
Lehtovirta M, Soininen H, Helisalmi S, Mannermaa A, Helkala EL, Hartikainen P, et al. Clinical and neuropsychological characteristics in familial and sporadic Alzheimer’s disease: Relation to apolipoprotein E polymorphism. Neurology. 1996;46:413-9. doi: http://dx.doi.org/10.1212/WNL.46.2.413
Yoshitake T, Kiyohara Y, Kato I, Ohmura T, Iwamoto H, Nakayama K, et al. Incidence and risk factors of vascular dementia and Alzheimer’s disease in a defined elderly Japanese population: The Hisayama Study. Neurology. 1995;45:1161-8. doi: http://dx.doi.org/10.1212/WNL.45.6.1161
Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance M, Enghild J, Salvensen GS, et al. Apolipoprotein E: High-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci U S A. 1993;90:1977-81. doi: http://dx.doi.org/10.1073/pnas.90.5.1977
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2009;32(Suppl.1):S62-7. doi: http://dx.doi.org/10.2337/dc09-S062
Kuzuya T, Nakagawa S, Satoh J, Kanazawa Y, Iwamoto Y, Kobayashi M, et al. Report of the Committee on the classification and diagnostic criteria of diabetes mellitus. Diabetes Res Clin Pract. 2002;55:65-85. doi: http://dx.doi.org/10.1016/S0168-8227(01)00365-5
Ryden L, Standl E, Bartnik M, van den Berghe G, Betteridge J, de Boer MJ, et al. Guidelines on diabetes,pre-diabetes, and cardiovascular diseases: Executive summary. The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD). Eur Heart J. 2007;28:88-136. PMid:17220161
Danaei G, Finucane MM, Lu Y, Singh GM, Cowan MJ, Paciorek CJ, et al. National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: Systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants. Lancet. 2011;378:31-40. doi: http://dx.doi.org/10.1016/S0140-6736(11)60679-X
Lorenzo C, Williams K, Hunt KJ, Haffner SM. The National Cholesterol Education Program - Adult Treatment Panel III, International Diabetes Federation, and World Health Organization definitions of the metabolic syndrome as predictors of incident cardiovascular disease and diabetes. Diabetes Care. 2007;30:8-13. doi: http://dx.doi.org/10.2337/dc06-1414
WHO. Diabetes. Geneve: WHO; 2011. Accessed: September 15, 2011. Disponible en: http://www.who.int/mediacentre/factsheets/fs312/en/index.html
Aschner P. Diabetes trends in Latin America. Diabetes Metab Res Rev. 2002;18(Suppl.3):S27-31. doi: http://dx.doi.org/10.1002/dmrr.280
Alzheimer’s Disease Association. Standards of medical care in diabetes -2011. Diabetes Care. 2011;34(Suppl.1):S11-61. doi: http://dx.doi.org/10.2337/dc11-S011
Ohara T, Doi Y, Ninomiya T, Hirakawa Y, Hata J, Iwaki T, et al. Glucose tolerance status and risk of dementia in the community: The Hisayama Study. Neurology. 2011;77:1126-34. doi: http://dx.doi.org/10.1212/WNL.0b013e31822f0435
Peila R, Rodríguez BL, Launer LJ. Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: The Honolulu-Asia Aging Study. Diabetes. 2002;51:1256-62. doi: http://dx.doi.org/10.2337/diabetes.51.4.1256
Kuusisto J, Koivisto K, Mykkanen L, Helkala EL, Vanhanen M, Hänninen T, et al. Essential hypertension and cognitive function. The role of hyperinsulinemia. Hypertension. 1993;22:771-9. doi: http://dx.doi.org/10.1161/01.HYP.22.5.771
Leibson CL, Rocca WA, Hanson VA, Cha R, Kokmen E, O’Brien PC, et al. Risk of dementia among persons with diabetes mellitus: A population-based cohort study. Am J Epidemiol. 1997;145:301-8. doi: http://dx.doi.org/10.1093/oxfordjournals.aje.a009106
Ott A, Stolk RP, van Harskamp F, Pols HA, Hofman A, Breteler MM. Diabetes mellitus and the risk of dementia: The Rotterdam Study. Neurology. 1999;53:1937-42.
doi: http://dx.doi.org/10.1212/WNL.53.9.1937
Martins IJ, Hone E, Foster JK, Sunram-Lea SI, Gnjec A, Fuller SJ, et al. Apolipoprotein E, cholesterol metabolism, diabetes, and the convergence of risk factors for Alzheimer’s disease and cardiovascular disease. Mol Psychiatry. 2006;11:721-36. doi: http://dx.doi.org/10.1038/sj.mp.4001854
Messier C. Diabetes, Alzheimer’s disease and apolipoprotein genotype. Exp Gerontol. 2003;38:941-6. doi: http://dx.doi.org/10.1016/S0531-5565(03)00153-0
Mahley RW, Huang Y. Apolipoprotein (apo) E4 and Alzheimer’s disease: Unique conformational and biophysical properties of apoE4 can modulate neuropathology. Acta Neurol Scand Suppl. 2006;185:8-14. doi: http://dx.doi.org/10.1111/j.1600-0404.2006.00679.x
Mahley RW, Huang Y, Weisgraber KH. Putting cholesterol in its place: apoE and reverse cholesterol transport. J Clin Invest. 2006;116:1226-9. doi: http://dx.doi.org/10.1172/JCI28632
Mahley RW, Weisgraber KH, Huang Y. Apolipoprotein E4: A causative factor and therapeutic target in neuropathology, including Alzheimer’s disease. Proc Natl Acad Sci U S A. 2006;103:5644-51. doi: http://dx.doi.org/10.1073/pnas.0600549103
Powell DS, Maksoud H, Charge SB, Moffitt JH, Desai M, Da Silva Fihlo RL, et al. Apolipoprotein E genotype, islet amyloid deposition and severity of type 2 diabetes. Diabetes Res Clin Pract. 2003;60:105-10. doi: http://dx.doi.org/10.1016/S0168-8227(02)00281-4
Edland SD. Insulin-degrading enzyme, apolipoprotein E, and Alzheimer’s disease. J Mol Neurosci. 2004;23:213-7. doi: http://dx.doi.org/10.1385/JMN:23:3:213
Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science. 1993;261:921-3. doi: http://dx.doi.org/10.1126/science.8346443
Levy ML, Cummings JL, Fairbanks LA, Sultzer DL, Small GW. Apolipoprotein E genotype and noncognitive symptoms in Alzheimer’s disease. Biol Psychiatry. 1999;45:422-5. doi: http://dx.doi.org/10.1016/S0006-3223(98)00041-9
Forero DA, Pinzón J, Arboleda GH, Yunis JJ, Álvarez C, Cataño N, et al. Analysis of common polymorphisms in angiotensin-converting enzyme and apolipoprotein E genes and human longevity in Colombia. Arch Med Res. 2006;37:890-4. doi: http://dx.doi.org/10.1016/j.arcmed.2006.04.001
Callas N, Poveda E, Baracaldo C, Hernández P, Castillo C, Guerra M. Polimorfismo genético de la apolipoproteína E en un grupo de escolares del centro-oriente colombiano: comparación con las concentraciones plasmáticas de lípidos y apolipoproteínas. Biomédica. 2007;27:526-36. PMid:18320120
Hernández-Fonseca JP, Rincón J, Pedreanez A, Viera N, Arcaya JL, Carrizo E, et al. Structural and ultrastructural analysis of cerebral cortex, cerebellum, and hypothalamus from diabetic rats. Exp Diabetes Res. 2009;2009:329632.
Sasaki N, Fukatsu R, Tsuzuki K, Hayashi Y, Yoshida T, Fujii N, et al. Advanced glycation end products in Alzheimer’s disease and other neurodegenerative diseases. Am J Pathol. 1998;153:1149-55. doi: http://dx.doi.org/10.1016/S0002-9440(10)65659-3
Brownlee M. Advanced protein glycosylation in diabetes and aging. Annu Rev Med. 1995;46:223-34. doi: http://dx.doi.org/10.1146/annurev.med.46.1.223
Yan SD, Chen X, Schmidt AM, Brett J, Godman G, Zou YS, et al. Glycated tau protein in Alzheimer disease: A mechanism for induction of oxidant stress. Proc Natl Acad Sci U S A. 1994;91:7787-91. doi: http://dx.doi.org/10.1073/pnas.91.16.7787
Klein JP, Waxman SG. The brain in diabetes: Molecular changes in neurons and their implications for end-organ damage. Lancet Neurol. 2003;2:548-54. doi: http://dx.doi.org/10.1016/S1474-4422(03)00503-9
Francis PT, Palmer AM, Snape M, Wilcock GK. The cholinergic hypothesis of Alzheimer’s disease: A review of progress. J Neurol Neurosurg Psychiatry. 1999;66:137-47. doi: http://dx.doi.org/10.1136/jnnp.66.2.137
Nitsch RM. From acetylcholine to amyloid: Neurotransmitters and the pathology of Alzheimer’s disease. Neurodegeneration. 1996;5:477-82. doi: http://dx.doi.org/10.1006/neur.1996.0066
Craft S. The role of metabolic disorders in Alzheimer disease and vascular dementia: Two roads converged. Arch Neurol. 2009;66:300-5.
doi: http://dx.doi.org/10.1001/archneurol.2009.27
Kameyama M, Fushimi H, Udaka F. Diabetes mellitus and cerebral vascular disease. Diabetes Res Clin Pract. 1994;24(Suppl.):S205-8. doi: http://dx.doi.org/10.1016/0168-8227(94)90250-X
Biessels GJ, Staekenborg S, Brunner E, Brayne C, Scheltens P. Risk of dementia in diabetes mellitus: A systematic review. Lancet Neurol. 2006;5:64-74. doi: http://dx.doi.org/10.1016/S1474-4422(05)70284-2
Biessels GJ, Kappelle LJ. Increased risk of Alzheimer’s disease in type II diabetes: Insulin resistance of the brain or insulin-induced amyloid pathology? Biochem Soc Trans. 2005;33:1041-4. doi: http://dx.doi.org/10.1042/BST20051041
Querfurth HW, LaFerla FM. Alzheimer’s disease. N Engl J Med. 2010;362:329-44. doi: http://dx.doi.org/10.1056/NEJMra0909142
Craft S, Watson GS. Insulin and neurodegenerative disease: Shared and specific mechanisms. Lancet Neurol. 2004;3:169-78. doi: http://dx.doi.org/10.1016/S1474-4422(04)00681-7
Smith MA, Sayre LM, Monnier VM, Perry G. Radical AGEing in Alzheimer’s disease. Trends Neurosci. 1995;18:172-6. doi: http://dx.doi.org/10.1016/0166-2236(95)93897-7
Irie F, Fitzpatrick AL, López OL, Kuller LH, Peila R, Newman AB, et al. Enhanced risk for Alzheimer disease in persons with type 2 diabetes and APOE epsilon4: The Cardiovascular Health Study Cognition Study. Arch Neurol. 2008;65:89-93. doi: http://dx.doi.org/10.1001/archneurol.2007.29
Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215. doi: http://dx.doi.org/10.1093/nar/16.3.1215
Hixson JE, Vernier DT. Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res. 1990;31:545-8. PMid:2341813
Panza F, Frisardi V, Capurso C, Imbimbo BP, Vendemiale G, Santamato A, et al. Metabolic syndrome and cognitive impairment: Current epidemiology and possible underlying mechanisms. J Alzheimers Dis. 2011;21:691-724.
Kalaria RN, Maestre GE, Arizaga R, Friedland RP, Galasko D, Santamato A, et al. Alzheimer’s disease and vascular dementia in developing countries: Prevalence, management, and risk factors. Lancet Neurol. 2008;7:812-26. doi: http://dx.doi.org/10.1016/S1474-4422(08)70169-8
Qiu C, von Strauss E, Fastbom J, Winblad B, Fratiglioni L. Low blood pressure and risk of dementia in the Kungsholmen project: A 6-year follow-up study. Arch Neurol. 2003;60:223-8. doi: http://dx.doi.org/10.1001/archneur.60.2.223
Qiu C, Winblad B, Viitanen M, Fratiglioni L. Pulse pressure and risk of Alzheimer disease in persons aged 75 years and older: A community-based, longitudinal study. Stroke. 2003;34:594-9. doi: http://dx.doi.org/10.1161/01.STR.0000060127.96986.F4
Strachan MW, Reynolds RM, Marioni RE, Price JF. Cognitive function, dementia and type 2 diabetes mellitus in the elderly. Nat Rev Endocrinol. 2011;7:108-14. doi: http://dx.doi.org/10.1038/nrendo.2010.228
Wannamethee SG, Shaper AG, Lennon L, Morris RW. Metabolic syndrome Vs. Framingham risk score for prediction of coronary heart disease, stroke, and type 2 diabetes mellitus. Arch Intern Med. 2005;165:2644-50. doi: http://dx.doi.org/10.1001/archinte.165.22.2644
Callahan A, Amarenco P, Goldstein LB, Sillesen H, Messig M, Samsa GP, et al. Risk of stroke and cardiovascular events after ischemic stroke or transient ischemic attack in patients with type 2 diabetes or metabolic syndrome: Secondary analysis of the stroke prevention by aggressive reduction in cholesterol levels (SPARCL) trial. Arch Neurol. 2011;68:1245-51. doi: http://dx.doi.org/10.1001/archneurol.2011.146
Ott A, Slooter AJ, Hofman A, van Harskamp F, Witteman JC, Van Broeckhoven C, et al. Smoking and risk of dementia and Alzheimer’s disease in a population-based cohort study: The Rotterdam Study. Lancet. 1998;351:1840-3. doi: http://dx.doi.org/10.1016/S0140-6736(97)07541-7
Peters R, Poulter R, Warner J, Beckett N, Burch L, Bulpitt C. Smoking, dementia and cognitive decline in the elderly, a systematic review. BMC Geriatr. 2008;8:36. doi: http://dx.doi.org/10.1186/1471-2318-8-36
Reitz C, den Heijer T, van Duijn C, Hofman A, Breteler MM. Relation between smoking and risk of dementia and Alzheimer disease: The Rotterdam Study. Neurology. 2007;69:998-1005. doi: http://dx.doi.org/10.1212/01.wnl.0000271395.29695.9a
Anstey KJ, von Sanden C, Salim A, O’Kearney R. Smoking as a risk factor for dementia and cognitive decline: A meta-analysis of prospective studies. Am J Epidemiol. 2007;166:367-78. doi: http://dx.doi.org/10.1093/aje/kwm116
Debanne SM, Rowland DY, Riedel TM, Cleves MA. Association of Alzheimer’s disease and smoking: The case for sibling controls. J Am Geriatr Soc. 2000;48:800-6. PMid:10894320
Doll R, Peto R, Boreham J, Sutherland I. Smoking and dementia in male British doctors: Prospective study. BMJ. 2000;320:1097-102. doi: http://dx.doi.org/10.1136/bmj.320.7242.1097
Hill JW, Futterman R, Duttagupta S, Mastey V, Lloyd JR, Fillit H. Alzheimer’s disease and related dementias increase costs of comorbidities in managed Medicare. Neurology. 2002;58:62-70. doi: http://dx.doi.org/10.1212/WNL.58.1.62
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