The Relation between Apolipoprotein E4 Genotype and Vascular Dementia


Most studies investigating genetics of dementia have focused on Alzheimer’s disease, but little is known about the genetics of vascular dementia (VD). The aim of this study was to identify the association between Apolipoprotein E4 (Apo E4) genotype and VD in cerebrally infarcted patients. The study was conducted on 100 patients with cerebral infarction: 50 had VD (cases) and 50 didn’t have dementia (controls). Diagnosis of VD was based on Mini-Mental State Examination, Cambridge Cognitive Examination (CAMCOG), the Diagnostic and Statistical Manual of Mental Disorders 4th edition criteria for the diagnosis of VD (DSM-IV), Hachinski Ischemic Score, and computed tomography of the brain (CT brain). Apo E4 allele was assessed through DNA genotyping. The study showed that hypertension (p = 0.027, OR = 4.71), diabetes mellitus (p = 0.003, OR = 6.05) and Apo E4 allele (p = 0.017, OR = 13.39) were the independent risk factors of VD among studied participants. The study concluded that cerebrally infarcted patients with Apo E4 genotype are at high risk of developing VD.

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Abdel Rahman, T. and Shehata, S. (2014) The Relation between Apolipoprotein E4 Genotype and Vascular Dementia. Advances in Aging Research, 3, 208-215. doi: 10.4236/aar.2014.33029.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Ruitenberg, A., Ott, A., van Swieten, J.C., Hofman, A. and Breteler, M.M. (2001) Incidence of Dementia: Does Gender Make a Difference? Neurobiology of Aging, 22, 575-580.
[2] Román, G.C. (2002) Vascular Dementia Revisited: Diagnosis, Pathogenesis, Treatment, and Prevention. Medical Clinics of North America, 86, 477-499.
[3] Argyri, L., Dafnis, I., Theodossiou, T.A., Gantz, D., Stratikos, E. and Chroni, A. (2014 ) Molecular Basis for Increased Risk for Late-Onset Alzheimer Disease Due to the Naturally Occurring L28P Mutation in Apolipoprotein E4. The Journal of Biological Chemistry, 289, 12931-12945.
[4] Joutel, A., et al. (1996) Notch3 Mutations in CADASIL, a Hereditary Adult-Onset Condition Causing Stroke and Dementia. Nature, 383, 707-710.
[5] Abboud, S., et al. (2008) Associations of Apolipoprotein E Gene with Ischemic Stroke and Intracranial Atherosclerosis. European Journal of Human Genetics, 16, 955-960.
[6] Yin, Y.-W., Li, J.-C., Wang, J.-Z., Li, B.-H., Pi, Y., Yang, Q.-W., Fang, C.-Q., Gao, C.-Y. and Zhang, L.-L. (2012) Association between Apolipoprotein E Gene Polymorphism and the Risk of Vascular Dementia: A Meta-Analysis. Neuroscience Letters, 514, 6-11.
[7] Baum, L., Lam, L.C., Kwok, T., Lee, J., Chiu, H.F., Mok, V.C., Wong, A., Chen, X., Cheung, W.S., Pang, C.P., Ma, S.L., Tang, N.L., Wong, K.S. and Ng, H.K. (2006) Apolipoprotein E Epsilon 4 Allele Is Associated with Vascular Dementia. Dementia and Geriatric Cognitive Disorders, 22, 301-305.
[8] Chuang, Y.F., Hayden, K.M., Norton, M.C., Tschanz, J., Breitner, J.C.S., Welsh-Bohmer, K.A. and Zandi, P.P. (2010) Association between APOE Epsilon4 Allele and Vascular Dementia: The Cache County Study. Dementia and Geriatric Cognitive Disorders, 29, 248-253.
[9] Engelborghs, S., Dermaut, B., Goeman, J., Saerens, J., Marien, P., Pickut, B.A., Van den Broeck, M., Serneels, S., Cruts, M., Van Broeckhoven, C. and De Deyn, P.P. (2003) Prospective Belgian Study of Neurodegenerative and Vascular Dementia: APOE Genotype Effects. Journal of Neurology, Neurosurgery Psychiatry, 74, 1148-1151.
[10] World Health Organization (1995) Physical Status: The Use and Interpretation of Anthropometry: Report of a WHO Expert Committee. Technical report series 854, Geneva.
[11] Sheikh, J.A., Yesavage, J.A. (1986) Recent Finding and Development of a Shorter Version. In Brinn, T.L., Ed., Clinical Gerontology: A Guide to Assessment and Intervention, Hawarth Press, New York, 165-173.
[12] Guidelines Subcommittee, World Health Organization-International Society of Hypertension (1999) Guidelines for the Management of Hypertension. Journal of Hypertension, 17, 151-183.
[13] American Diabetes Association (2003) Screening for Type 2 Diabetes, Diabetic Care, 26, S21-S24.
[14] Third Report of the National Cholesterol Education Program (NCEP) (2001) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Executive Summary. National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health.
[15] Folstein, M.F., Folstein, S.E. and McHugh, P.R. (1975) “Mini-Mental State” A Practical Method for Grading the Cognitive State of Patients for the Clinician. Journal of Psychiatric Research, 12, 189-198.
[16] Williams, J.G., Huppert, F.A., Matthews, F.E. and Nickson, J. (2003) Performance and Normative Values of a Concise Neuropsychological Test (CAMCOG) in an Elderly Population Sample. International Journal of Geriatric Psychiatry, 18, 631-644.
[17] American Psychiatric Association (2000) Diagnostic and Statistical Manual of Mental Disorders. 4th Edition, Text Revision, American Psychiatric Association, Washington DC.
[18] Hachiniski Merck Manual of Geriatrics. 2nd Edition, 1995, 1156. Version Modified from Hachinski, V.C., Iliff, L.D., Phil, M., et al. (1975) Cerebral Blood Flow in Dementia. Archives of Neurology, 32, 632-637.
[19] Miller, S., Dykes, D. and Polesky, H. (1988) A Simple Salting out Procedure for Extracting DNA from Human Nucleated Cells. Nucleic Acids Research, 16, 1215.
[20] Wenham, P.R., Price, W.H. and Blundell, G. (1991) Apolipoprotein E Genotyping by One-Stage PCR. Lancet, 337, 1158-1159.
[21] Davidson, Y., Gibbons, L., Purandare, N., Byrne, J., Hardicre, J., Wren, J., et al. (2006) Apolipoprotein E υ4 Allele Frequency in Vascular Dementia. Dementia and Geriatric Cognitive Disorders, 22, 15-19.
[22] Yang, J., Feng, G., Zhang, J., Hui, Z., Breen, G., St Clair, D. and He, L. (2001) Is APOE Gene a Risk Factor for Vascular Dementia in Han Chinese? International Journal of Molecular Medicine, 7, 217-219.
[23] Kim, K.W., Youn, J.C., Han, M.K., Paik, N.J., Lee, T.J., Park, J.H., et al. (2008) Lack of Association between Apolipoprotein E Polymorphism and Vascular Dementia in Koreans. Journal of Geriatric Psychiatry and Neurology, 21, 12-17.
[24] Lin, H.F., Lai, C.L., Tai, C.T., Lin, R.T. and Liu, C.K. (2004) Apolipoprotein E Polymorphism in Ischemic Cerebrovascular Diseases and Vascular Dementia Patients in Taiwan. Neuroepidemiology, 23, 129-134.
[25] Debette, S., Lambert, J.C., Gariépy, J., Fievet, N., Tzourio, C., Dartigues, J.F., Ritchie, K., Dupuy, A.M., Alpérovitch, A., Ducimetière, P., Amouyel, P. and Zureik, M. (2006) New Insight into the Association of Apolipoprotein E Genetic Variants with Carotid Plaques and Intima-Media Thickness. Stroke, 37, 2917-2923.
[26] Thambisetty, M., Beason-Held, L.L., An, Y., Kraut, M., Nalls, M., Hernandez, D.G., et al. (2010) APOE ε4 Genotype and Longitudinal Changes in Cerebral Blood Flow in Normal Aging. JAMA Neurology, 67, 93-98.
[27] Klein, R.C., Mace, B.E., Moore, S.D. and Sullivan, P.M. (2010) Progressive Loss of Synaptic Integrity in Human Apolipoprotein E4 Targeted Replacement Mice and Attenuation by Apolipoprotein E2. Neuroscience, 171, 1265-1272.
[28] Notkola, I.L., Sulkava, R., Pekkanen, J., Erkinjuntti, T., Ehnholm, C., Kivinen, P., Tuomilehto, J. and Nissinen, A. (1998) Serum Total Cholesterol, Apolipoprotein E Epsilon 4 Allele, and Alzheimer’s Disease. Neuroepidemiology, 17, 14-20.
[29] Prince, M., Lovestone, S., Cervilla, J., Joels, S., Powell, J., Russ, C. and Mann, A. (2000) The Association between APOE and Dementia Does Not Seem to Be Mediated by Vascular Factors. Neurology, 54, 397-402.
[30] O’Sullivan, M., Jones, D.K., Summers, P.E., Morris, R.G., Williams, S.C. and Markus, H.S. (2001) Evidence for Cortical “Disconnection” as a Mechanism of Age-Related Cognitive Decline. Neurology, 57, 632-638.
[31] Pantoni, L. (2010) Cerebral Small Vessel Disease: From Pathogenesis and Clinical Characteristics to Therapeutic Challenges. Lancet Neurology, 9, 689-701.
[32] Thong, J.Y., Hilal, S., Wang, Y., Soon, H.W., Dong, Y., Collinson, S.L., Anh, T.T., Ikram, M.K., Wong, T.Y., Venketasubramanian, N., Chen, C. and Qiu, A. (2013) Association of Silent Lacunar Infarct with Brain Atrophy and Cognitive Impairment. Journal of Neurology, Neurosurgery, and Psychiatry, 84, 1219-1225.
[33] Lanna, M.E., Alves, C.E., Sudo, F.K., Alves, G., Valente, L., Moreira, D.M., Cavalcanti, J.L. and Engelhardt, E. (2012) Cognitive Disconnective Syndrome by Single Strategic Strokes in Vascular Dementia. Journal of the Neurological Sciences, 322, 176-183.
[34] Van Straaten, E.C.W., Scheltens, P.H. and Barkhof, F. (2004) MRI and CT in the Diagnosis of Vascular Dementia. Journal of the Neurological Sciences, 226, 9-12.
[35] Igase, M., Kohara, K. and Miki, T. (2012) The Association between Hypertension and Dementia in the Elderly. International Journal of Hypertension, 2012, Article ID: 320648.
[36] Mayeda, E.R., Haan, M.N., Kanaya, A.M., Yaffe, K. and Neuhaus, J. (2013) Type 2 Diabetes and 10-Year Risk of Dementia and Cognitive Impairment among Older Mexican Americans. Diabetes Care, 36, 2600-2606.
[37] Tolppanen, A.M., Lavikainen, P., Solomon, A., Kivipelto, M., Uusitupa, M., Soininen, H. and Hartikainen, S. (2013) History of Medically Treated Diabetes and Risk of Alzheimer Disease in a Nationwide Case-Control Study. Diabetes Care, 36, 2015-2019.
[38] Dantoine, T.F., Debord, J., Merle, L., Lacroix-Ramiandrisoa, H., Bourzeix, L. and Charmes, J.P. (2002) Paraoxonase 1 Activity: A New Vascular Marker of Dementia? Annals of the New York Academy of Sciences, 977, 96-101.
[39] Zuliani, G., Ble, A., Zanca, R., Munari, M.R., Zurlo, A., Vavalle, C., Atti, A.R. and Fellin, R. (2001) Lipoprotein Profile in Older Patients with Vascular Dementia and Alzheimer’s Disease. BMC Geriatrics, 1, 5.
[40] Huseyin Doruk, Naharci, M.I., Bozoglu, E., Isik, A.T. and Kilic, S. (2010) The Relationship between Body Mass Index and Incidental Mild Cognitive Impairment, Alzheimer’s Disease, and Vascular Dementia in Elderly. The Journal of Nutrition, Health & Aging, 14, 834-838.
[41] Sánchez-Moreno, C., Jiménez-Escrig, A. and Martín, A. (2009) Stroke: Roles of B Vitamins, Homocysteine and Antioxidants. Nutrition Research Reviews, 22, 49-67.
[42] Chai, J., Chu, F.C.S., Chow, T.W. and Shum, N.C. (2008) Prevalence of Malnutrition and Its Risk Factors in Stroke Patients Residing in an Infirmary. Singapore Medical Journal, 49, 290-296.
[43] Mould, J. (2009) Nurses “Must” Control of the Nutritional Needs of Stroke Patients. British Journal of Nursing, 18, 1410-1414.
[44] Chaudhari, T.S., Verma, R., Garg, R.K., Singh, M.K., Malhotra, H.S. and Sharma, P.K. (2014) Clinico-Radiological Predictors of Vascular Cognitive Impairment (VCI) in Patients with Stroke: A Prospective Observational Study. Journal of the Neurological Sciences, 340, 150-158.
[45] Jack, C. (2012) Cardiovascular Risk Factors Promote Brain Hypoperfusion Leading to Cognitive Decline and Dementia. Cardiovascular Psychiatry and Neurology, 2012, Article ID: 367516.

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