Apolipoprotein E Polymorphism and Cognitive Function Change of the Elderly in a Rural Area, Korea

일개 농촌지역 노인의 아포지단백 E 다형성과 인지기능 변화

  • Kim, Sang-Kyu (Department of Preventive Medicine, Dongguk University, College of Medicine) ;
  • Hwang, Tae-Yoon (Department of Preventive Medicine and Public Health Yeungnam University, College of Medicine) ;
  • Lee, Kyeong-Soo (Department of Preventive Medicine and Public Health Yeungnam University, College of Medicine) ;
  • Kang, Pock-Soo (Department of Preventive Medicine and Public Health Yeungnam University, College of Medicine) ;
  • Cho, Hee-Soon (Department of Laboratory Medicine Yeungnam University, College of Medicine) ;
  • Bae, Young-Kyung (Department of Pathology Yeungnam University, College of Medicine)
  • 김상규 (동국대학교 의과대학 예방의학교실) ;
  • 황태윤 (영남대학교 의과대학 예방의학교실) ;
  • 이경수 (영남대학교 의과대학 예방의학교실) ;
  • 강복수 (영남대학교 의과대학 예방의학교실) ;
  • 조희순 (영남대학교 진단검사의학교실) ;
  • 배영경 (영남대학교 병리학교실)
  • Published : 2009.07.31


Objectives : The aim of this study is to examine the cognitive function change related to aging, the incidence of cognitive impairment, and the association between apolipoprotein E polymorphism and cognitive impairment through a follow-up of the elderly with normal cognitive ability at baseline. Methods : Two hundred and fifteen subjects aged 65 and over were surveyed in February, 1998 (baseline survey), and their cognitive function was assessed again in 2003 1st follow-up) and the once again in 2006 (2nd follow-up). Ninety one subjects completed all surveys up through the 2nd follow-up and their cognitive function scores using MMSE-K (Korean Version of the Mini-Mental State Examination) and the distribution of apolipoprotein E allele were analyzed. Results : The cognitive function scores decreased with aging and the difference between baseline and the 2nd follow-up scores of the study increased with the age group. The incidence rate of cognitive impairment through an 8-year follow-up was 38.5% and higher in older age groups. Age was the only significant factor for incidence of cognitive impairment, but there was no significant association between apolipoprotein E genotype and incidence of cognitive impairment. Conclusions : The cognition of the elderly decreased with aging and the association of apolipoprotein E genotype with incidence of cognitive impairment was not significant in this study. To confirm the association between apolipoprotein E polymorphism and incidence of cognitive impairment further studies will be needed.


  1. Korean Association of Geriatric Psychiatry. Geriatric Psychiatry. Seoul: Jungang Moonhwa Co.; 2004. p. 10-14. (Korean)
  2. Kim JS, Lee SI, Jeong IS, Chung YI, Hwang IK, Yih BS, et al. Prevalence rate of cognitive impairment and dementia among the elderly in Busan. Korean J Prev Med 2003; 36(1): 63-71. (Korean)
  3. Shin HY, Chung EK, Rhee JA, Yoon JS, Kim JM. Prevalence and related factors of dementia in an urban elderly population using a new screening method. J Prev Med Public Health 2005; 38(3): 351-358. (Korean)
  4. Kim JK, Kim SU, Hahm BJ, Lee JY, Cho MJ. Three and half year follow-up study on a rural elderly cohort: Prevalence, incidences, and service utilization of dementia and depressive disorders. J Korean Geriatr Psychiatry 2002; 6(2): 88-96. (Korean)
  5. Park JH. Epidemiology of dementia in elderly people in Jookjang-Myun, Pohang, Kyungpook province: 1990-1999. J Korean Geriatr Psychiatry 2000; 4(1): 50-57. (Korean)
  6. Johansson B, Zarit SH. Early cognitive markers of the incidence of dementia and mortality: A longitudinal population-based study of the oldest old. Int J Geriatr Psychiatry 1997; 12(1): 53-59 https://doi.org/10.1002/(SICI)1099-1166(199701)12:1<53::AID-GPS507>3.0.CO;2-M
  7. Park JH. Early diagnosis of dementia. J Korean Acad Fam Med 2004; 25(9): 653-660. (Korean)
  8. Kim SK, Kang PS, Hwang TY, Sakong J, Lee KS. Change of cognitive function and associated factors among the rural elderly: A 5-year followup study. J Prev Med Public Health 2007; 40(2): 162-168. (Korean) https://doi.org/10.3961/jpmph.2007.40.2.162
  9. Park JH. Two consecutive 6-year follow-ups of the MMSEK in the rural elderly. J Korean Neuropsychiatr Assoc 2005; 44(5): 612-618. (Korean)
  10. Stewart R, Liolitsa D. Type 2 diabetes mellitus, cognitive impairment and dementia. Diabet Med 1999; 16(2): 93-112 https://doi.org/10.1046/j.1464-5491.1999.00027.x
  11. van Oijen M, de Jong FJ, Witteman JC, Hofman A, Koudstaal PJ, Breteler MM. Atherosclerosis and risk for dementia. Ann Neurol 2007; 61(5): 403-410 https://doi.org/10.1002/ana.21073
  12. Stella F, Banzato CE, Gasparetto Se EV, Scudeler JL, Pacheco JL, Kajita RT. Risk factors for vascular dementia in elderly psychiatric outpatients with preserved cognitive functions. J Neurol Sci 2007; 257(1-2): 247-249 https://doi.org/10.1016/j.jns.2007.01.035
  13. Horejsi B, Ceska R. Apolipoproteins and atherosclerosis. Apolipoprotein E and apolipoprotein(a) as candidate genes of premature development of atherosclerosis. Physiol Res 2000; 49 Suppl 1: S63-69
  14. Kim YS, Paeng JR, Woo JT, Kim SW, Yang IM, Kim JW, et al. Apolipoprotein E genotypes of normal and hyperlipidemic subjects. J Korean Med Sci 1993; 8(4): 262-266. (Korean) https://doi.org/10.3346/jkms.1993.8.4.262
  15. Jonker C, Schmand B, Lindeboom J, Havekes LM, Launer LJ. Association between apolipoprotein E epsilon4 and the rate of cognitive decline in community-dwelling elderly individuals with and without dementia. Arch Neurol 1998; 55(8): 1065-1069 https://doi.org/10.1001/archneur.55.8.1065
  16. Yip AG, Brayne C, Easton D, Rubinsztein DC. Apolipoprotein E4 is only a weak predictor of dementia and cognitive decline in the general population. J Med Genet 2002; 39(9): 639-643 https://doi.org/10.1136/jmg.39.9.639
  17. Kim SH, Han SY, Choi YS, Lee KS. Apolipoprotein E gene and alpha 1-antichymotrypsin gene in brain of sporadic Alzheimer s disease. J Korean Neurol Assoc 2002; 20(6): 641-651. (Korean)
  18. Kang HU, Park MY. Apolipoprotein E4 allele frequency in Korean patients with vascular dementia. J Korean Dement Assoc 2002; 1(1): 34-38. (Korean)
  19. Son EJ, Kim JM, Kim YS, Kim BC, Kim MK, Cho KH. Relationships of apolipoprotein E genotypes with vascular risk factors in patients with Alzheimer' s disease. J Korean Neurol Assoc 2003; 21(1): 41-45. (Korean)
  20. Kim KW, Youn JC, Jhoo JH, Lee DY, Lee KU, Lee JH, et al. Apolipoprotein E epsilon 4 allele is not associated with the cognitive impairment in community-dwelling normal elderly individuals. Int J Geriatr Psychiatry 2002; 17(7): 635-640 https://doi.org/10.1002/gps.664
  21. Kim KR, Lee KS, Kim EA, Cheong HK, Oh BH, Hong CH. The effect of the Apo E genotype on the association between head circumference and cognition. Am J Geriatr Psychiatry 2008; 16(10): 819-825 https://doi.org/10.1097/JGP.0b013e3181800551
  22. Park JH, Kwon YC. Standardization of Korean version of the Mini-Mental State Examination (MMSE-K) for use in the elderly: Part . diagnostic validity. J Korean Neuropsychiatr Assoc 1989; 28(3): 508-513. (Korean)
  23. Park YM, Jeon YM, Kwon GC, Koo SH, Park JW. Analysis of apolipoprotein E genotypes in several demetial disease. Korean J Clin Pathol 1999; 19(6): 642-646. (Korean)
  24. Jorm A, Korten A, Henderson A. The Prevalence of dementia: A quantitative integration of the literature. Acta Psychiatr Scand 1987; 76(5): 465-479 https://doi.org/10.1111/j.1600-0447.1987.tb02906.x
  25. Suh GH. Dementia in Korea: Trend and projection. J Korean Geriatr Psychiatry 2002; 6(2): 79-87. (Korean)
  26. Lee JH. Cause, evaluation and treatment of dementia-for primary care physician. J Korean Acad Fam Med 2001; 22(5): 619-628. (Korean)
  27. Auyeung TW, Kwok T, Lee J, Leung PC, Leung J, Woo J. Functional decline in cognitive impairment--the relationship between physical and cognitive function. Neuroepidemiology 2008; 31(3): 167-173 https://doi.org/10.1159/000154929
  28. Lavery LL, Dodge HH, Snitz B, Ganguli M. Cognitive decline and mortality in a community-based cohort: The Monongahela Valley Independent Elders Survey. J Am Geriatr Soc 2009; 57(1): 94-100 https://doi.org/10.1111/j.1532-5415.2008.02052.x
  29. Chan DC, Kasper JD, Black BS, Rabins PV. Clinical diagnosis of dementia, not behavioral and psychologic symptoms, is associated with psychotropic drug use in community-dwelling elders classified as having dementia. J Geriatr Psychiatry Neurol 2007; 20(2): 100-106 https://doi.org/10.1177/0891988706298628
  30. Park JH, Lee YH, Kim HC. A 6-year followup of cognitive function in a rural elderly population. J Korean Neuropsychiatr Assoc 1999; 38(1): 181-189. (Korean)
  31. Sim HS, Kim SM, Cho KH, Hong MH, Chang JA, Park YK. One year follow up study of the MMSE-K in the elderly. J Korean Geriatr Soc 1999; 3(2): 37-45. (Korean)
  32. So HY, Ju KO, Jung MH, Kim HY. Cognitive function of the urban elderly. Korean J Rehabil Nurs 2004; 7(2): 179-187. (Korean)
  33. Han L, Cole M, Bellavance F, McCusker J, Primeau F. Tracking cognitive decline in Alzheimer s disease using the mini-mental state examination: A meta-analysis. Int Psychogeriatr 2000; 12(2): 231-247 https://doi.org/10.1017/S1041610200006359
  34. Mitchell AJ. A meta-analysis of the accuracy of the mini-mental state examination in the detection of dementia and mild cognitive impairment. J Psychiatr Res 2009; 43(4): 411-431 https://doi.org/10.1016/j.jpsychires.2008.04.014
  35. Eslinger PJ, Swan GE, Carmelli D. Changes in Mini-Mental State Exam in communitydwelling older persons over 6 years: Relationship to health and neuropsychological measures. Neuroepidemiology 2003; 22(1): 23-30 https://doi.org/10.1159/000067113
  36. Paik Y, Chang D, Reardon C, Davies G, Mahley R, Taylor J. Nucleotide sequence and structure of the human apolipoprotein E gene. Proc Natl Acad Sci USA 1985; 82(10): 3445-3449 https://doi.org/10.1073/pnas.82.10.3445
  37. Kamboh M, Aston C, Ferrell R, Hamman R. Impact of apolipoprotein E polymorphism in determining interindividual variation in total cholesterol and low density lipoprotein cholesterol in Hispanics and non-Hispanic whites. Atherosclerosis 1993; 98(2): 201-211 https://doi.org/10.1016/0021-9150(93)90129-I
  38. Kozauer NA, Mielke MM, Chan GK, Rebok GW, Lyketsos CG. Apolipoprotein E genotype and lifetime cognitive decline. Int Psychogeriatr 2008; 20(1): 109-123 https://doi.org/10.1017/S104161020700587X
  39. Miyamoto M, Kodama C, Kinoshita T, Yamashita F, Hidaka S, Mizukami K, et al. Dementia and mild cognitive impairment among non-responders to a community survey. J Clin Neurosci 2009; 16(2): 270-276 https://doi.org/10.1016/j.jocn.2008.03.007
  40. Christensen MD, White HK. Dementia assessment and management. J Am Med Dir Assoc 2007; 8(3 Suppl 2): e89-98 https://doi.org/10.1016/j.jamda.2006.12.011