 |
 |
|
Home |
Current Issue |
Past Issues |
In the Clinic |
ACP Journal Club |
CME |
Collections |
Audio/Video |
Mobile |
Subscribe |
Tools |
Help |
ACP Online
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
6 August 2002 | Volume 137 Issue 3 | Pages 149-155
Background: Presence of the apolipoprotein E (apoE)
Objective: To study the relative importance and the putative relationship among the apoE
Design: Prospective population-based study.
Setting: Kuopio and Joensuu, eastern Finland.
Participants: Participants were derived from random population surveys from 1972, 1977, 1982, and 1987. A total of 1449 persons (73%), 65 to 79 years of age, participated in the reexamination in 1998 (mean follow-up, 21 years).
Measurements: Midlife blood pressure and total cholesterol level, apoE genotype, and development of Alzheimer disease during follow-up.
Results: The apoE
Conclusions: The association between the apoE
Editors' Notes
Context
Contribution
Implications
–The Editors
Author and Article Information
From University of Kuopio, and Kuopio University Hospital, Kuopio; North Karelia Central Hospital, Joensuu; and the National Public Health Institute, Helsinki, Finland.
Acknowledgments: The authors thank Petra Mäkinen for technical help and Veli Koistinen, Veikko Jokela, and Pirjo Halonen for consultations in statistical analysis.
Grant Support: By the Academy of Finland (grants 37573, 63645, 48138, 48950) and by erityisvaltionosuus (EVO) (grant 477268).
Requests for Single Reprints: Miia Kivipelto, MD, University of Kuopio, Department of Neuroscience and Neurology, PO Box 1627, 70211 Kuopio, Finland; e-mail, miia.kivipelto{at}uku.fi.
Potential Financial Conflicts of Interest: None disclosed.
Current Author Addresses: Drs. Kivipelto and Soininen: University of Kuopio, Department of Neuroscience and Neurology, PO Box 1627, 70211 Kuopio, Finland.
Dr. Helkala: University of Kuopio, Department of Public Health and General Practice, PO Box 1627, 70211 Kuopio, Finland.
Dr. Laakso: Kuopio University Hospital, Departments of Clinical Radiology and Neurology, PO Box 1777, 70211 Kuopio, Finland.
Dr. Hänninen: Kuopio University Hospital, Department of Neurology, PO Box 1777, 70211 Kuopio, Finland.
Dr. Hallikainen: Kuopio University Hospital, Department of Neurology, Building 4, PO Box 1777, 70211 Kuopio, Finland.
Dr. Alhainen: Memory Research Centre, Torikatu 17, 80100 Joensuu, Finland.
Ms. Iivonen: University of Kuopio, Department of Neuroscience and Neurology, PO Box 1627, 70211 Kuopio, Finland.
Dr. Mannermaa: Kuopio University Hospital, Chromosome and DNA Laboratory of the Division of Diagnostic Services, PO Box 1777, 70211 Kuopio, Finland.
Drs. Tuomilehto and Nissinen: National Public Health Institute, Diabetes and Genetic Epidemiology Unit, Mannerheimintie 166, 00300 Helsinki, Finland.
Author Contributions: Conception and design: M. Kivipelto, E.-L. Helkala, J. Tuomilehto, A. Nissinen, H. Soininen.
Analysis and interpretation of the data: M. Kivipelto, E.-L. Helkala, M.P. Laakso, J. Tuomilehto, A. Nissinen, H. Soininen.
Drafting of the article: M. Kivipelto, M.P. Laakso.
Critical revision of the article for important intellectual content: M. Kivipelto, E.-L. Helkala, M.P. Laakso, T. Hänninen, M. Hallikainen, K. Alhainen, S. Iivonen, A. Mannermaa, J. Tuomilehto, A. Nissinen, H. Soininen.
Final approval of the article: M. Kivipelto, E.-L. Helkala, M.P. Laakso, T. Hänninen, M. Hallikainen, K. Alhainen, S. Iivonen, A. Mannermaa, J. Tuomilehto, A. Nissinen, H. Soininen.
Statistical expertise: M. Kivipelto, E.-L. Helkala. ARTICLE
Apolipoprotein E
4 Allele, Elevated Midlife Total Cholesterol Level, and High Midlife Systolic Blood Pressure Are Independent Risk Factors for Late-Life Alzheimer Disease
4 allele, which is involved in cholesterol metabolism, is the most important genetic risk factor for Alzheimer disease. Elevated midlife values for total cholesterol level and blood pressure have been implicated recently as risk factors for Alzheimer disease. 4 allele, midlife total cholesterol level, and midlife blood pressure as risk factors for late-life Alzheimer disease. 4 allele was an independent risk factor for Alzheimer disease, even after adjustment for midlife vascular risk factors and other confounders (odds ratio, 2.1 [95% CI, 1.1 to 4.1]). Similarly, elevated midlife values for serum total cholesterol level (odds ratio, 2.8 [CI, 1.2 to 6.7]) and systolic blood pressure (odds ratio, 2.6 [CI, 1.1 to 6.6]) were independent risk factors for Alzheimer disease, even after adjustment for apoE genotype and other confounding factors. 4 allele and Alzheimer disease does not seem to be mediated by vascular factors. The apoE 4 allele, elevated midlife total cholesterol level, and high midlife systolic blood pressure are independent risk factors for Alzheimer disease. The risk for Alzheimer disease from treatable factors—elevated total cholesterol level and blood pressure—appears to be greater than that from the apoE 4 allele.
4 allele, elevated total cholesterol level, and hypertension are risk factors for late-life Alzheimer disease.
Related articles in Annals:
This article has been cited by other articles:
|
|
 |
|
  G. Hu, R. Antikainen, P. Jousilahti, M. Kivipelto, and J. Tuomilehto Total cholesterol and the risk of Parkinson disease Neurology, May 20, 2008; 70(21): 1972 - 1979. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Anstey, D. M. Lipnicki, and L.-F. Low Cholesterol as a Risk Factor for Dementia and Cognitive Decline: A Systematic Review of Prospective Studies With Meta-Analysis Am J Geriatr Psychiatry, May 1, 2008; 16(5): 343 - 354. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J Whalley, I. J Deary, J. M Starr, K. W Wahle, K. A Rance, V. J Bourne, and H. C Fox n-3 Fatty acid erythrocyte membrane content, APOE {varepsilon}4, and cognitive variation: an observational follow-up study in late adulthood Am. J. Clinical Nutrition, February 1, 2008; 87(2): 449 - 454. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Mielke, P. B. Rosenberg, J. Tschanz, L. Cook, C. Corcoran, K. M. Hayden, M. Norton, P. V. Rabins, R. C. Green, K. A. Welsh-Bohmer, et al. Vascular factors predict rate of progression in Alzheimer disease Neurology, November 6, 2007; 69(19): 1850 - 1858. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Furie and E. E. Smith Metabolic syndrome: A target for preventing leukoaraiosis and age-related dementia? Neurology, September 4, 2007; 69(10): 951 - 952. [Full Text] [PDF]
|
|
|
|
 |
|
 N. Scarmeas Invited Commentary: Lipoproteins and Dementia--Is It the Apolipoprotein A-I? Am. J. Epidemiol., May 1, 2007; 165(9): 993 - 997. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Guizzetti and L. Costa Cholesterol homeostasis in the developing brain: a possible new target for ethanol Human and Experimental Toxicology, April 1, 2007; 26(4): 355 - 360. [Abstract] [PDF]
|
|
|
|
|
|
A. Solomon, I. Kareholt, T. Ngandu, B. Winblad, A. Nissinen, J. Tuomilehto, H. Soininen, and M. Kivipelto Serum cholesterol changes after midlife and late-life cognition: Twenty-one-year follow-up study Neurology, March 6, 2007; 68(10): 751 - 756. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Stewart, L. R. White, Q.-L. Xue, and L. J. Launer Twenty-six-Year Change in Total Cholesterol Levels and Incident Dementia: The Honolulu-Asia Aging Study Arch Neurol, January 1, 2007; 64(1): 103 - 107. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Borroni, M. Grassi, C. Costanzi, S. Archetti, L. Caimi, and A. Padovani APOE Genotype and Cholesterol Levels in Lewy Body Dementia and Alzheimer Disease: Investigating Genotype-Phenotype Effect on Disease Risk Am J Geriatr Psychiatry, December 1, 2006; 14(12): 1022 - 1031. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Burns and J. O'Brien Clinical practice with anti-dementia drugs: a consensus statement from British Association for Psychopharmacology. J Psychopharmacol, November 1, 2006; 20(6): 732 - 755. [Abstract] [PDF]
|
|
|
|
|
|
F. Bursi, W. A. Rocca, J. M. Killian, S. A. Weston, D. S. Knopman, S. J. Jacobsen, and V. L. Roger Heart Disease and Dementia: A Population-based Study Am. J. Epidemiol., January 15, 2006; 163(2): 135 - 141. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. F. Mitchell, J. A. Vita, M. G. Larson, H. Parise, M. J. Keyes, E. Warner, R. S. Vasan, D. Levy, and E. J. Benjamin Cross-Sectional Relations of Peripheral Microvascular Function, Cardiovascular Disease Risk Factors, and Aortic Stiffness: The Framingham Heart Study Circulation, December 13, 2005; 112(24): 3722 - 3728. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W M van der Flier and P Scheltens Epidemiology and risk factors of dementia J. Neurol. Neurosurg. Psychiatry, December 1, 2005; 76(suppl_5): v2 - v7. [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Cole, A. Grudzien, I. O. Manhart, B. L. Kelly, H. Oakley, and R. Vassar Statins Cause Intracellular Accumulation of Amyloid Precursor Protein, {beta}-Secretase-cleaved Fragments, and Amyloid {beta}-Peptide via an Isoprenoid-dependent Mechanism J. Biol. Chem., May 13, 2005; 280(19): 18755 - 18770. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Dufouil, F. Richard, N. Fievet, J. F. Dartigues, K. Ritchie, C. Tzourio, P. Amouyel, and A. Alperovitch APOE genotype, cholesterol level, lipid-lowering treatment, and dementia: The Three-City Study Neurology, May 10, 2005; 64(9): 1531 - 1538. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Lane and M. R. Farlow Lipid homeostasis and apolipoprotein E in the development and progression of Alzheimer's disease J. Lipid Res., May 1, 2005; 46(5): 949 - 968. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Purandare, C. Ballard, and A. Burns Preventing dementia Advan. Psychiatr. Treat., May 1, 2005; 11(3): 176 - 183. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Tuomilehto Primary Prevention of Type 2 Diabetes: Lifestyle Intervention Works and Saves Money, but What Should Be Done with Smokers? Ann Intern Med, March 1, 2005; 142(5): 381 - 383. [Full Text] [PDF]
|
|
|
|
|
|
R. P. Koldamova, I. M. Lefterov, M. Staufenbiel, D. Wolfe, S. Huang, J. C. Glorioso, M. Walter, M. G. Roth, and J. S. Lazo The Liver X Receptor Ligand T0901317 Decreases Amyloid {beta} Production in Vitro and in a Mouse Model of Alzheimer's Disease J. Biol. Chem., February 11, 2005; 280(6): 4079 - 4088. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. K. Blair, A. R. Folsom, D. S. Knopman, M. S. Bray, T. H. Mosley, E. Boerwinkle, and for the Atherosclerosis Risk in Communities Study APOE genotype and cognitive decline in a middle-aged cohort Neurology, January 25, 2005; 64(2): 268 - 276. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Hajjar, H. Catoe, S. Sixta, R. Boland, D. Johnson, V. Hirth, D. Wieland, and P. Eleazer Cross-Sectional and Longitudinal Association Between Antihypertensive Medications and Cognitive Impairment in an Elderly Population J. Gerontol. A Biol. Sci. Med. Sci., January 1, 2005; 60(1): 67 - 73. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Elkins, E. S. O'Meara, W. T. Longstreth Jr., M. C. Carlson, T. A. Manolio, and S. C. Johnston Stroke risk factors and loss of high cognitive function Neurology, September 14, 2004; 63(5): 793 - 799. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Zhang, A. Matsunaga, K. Saku, S. Nakano, and T. Yamada Associations Among Plasma Lipoprotein Subfractions as Characterized by Analytical Capillary Isotachophoresis, Apolipoprotein E Phenotype, Alzheimer Disease, and Mild Cognitive Impairment Arterioscler. Thromb. Vasc. Biol., August 1, 2004; 24(8): e144 - e144. [Full Text] [PDF]
|
|
|
|
|
|
L. E. Hebert, P. A. Scherr, D. A. Bennett, J. L. Bienias, R. S. Wilson, M. C. Morris, and D. A. Evans Blood pressure and late-life cognitive function change: A biracial longitudinal population study Neurology, June 8, 2004; 62(11): 2021 - 2024. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C Qiu, M Kivipelto, H Aguero-Torres, B Winblad, and L Fratiglioni Risk and protective effects of the APOE gene towards Alzheimer's disease in the Kungsholmen project: variation by age and sex J. Neurol. Neurosurg. Psychiatry, June 1, 2004; 75(6): 828 - 833. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Morris, D. A. Evans, J. L. Bienias, C. C. Tangney, and R. S. Wilson Dietary fat intake and 6-year cognitive change in an older biracial community population Neurology, May 11, 2004; 62(9): 1573 - 1579. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Elkins, V. C. Douglas, and S. C. Johnston Alzheimer disease risk and genetic variation in ACE: A meta-analysis Neurology, February 10, 2004; 62(3): 363 - 368. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J Miller and R. Chacko The Role of Cholesterol and Statins in Alzheimer's Disease Ann. Pharmacother., January 1, 2004; 38(1): 91 - 98. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Roher, C. Esh, T. A. Kokjohn, W. Kalback, D. C. Luehrs, J. D. Seward, L. I. Sue, and T. G. Beach Circle of Willis Atherosclerosis Is a Risk Factor for Sporadic Alzheimer's Disease Arterioscler. Thromb. Vasc. Biol., November 1, 2003; 23(11): 2055 - 2062. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. R. Merikangas and N. Risch Will the Genomics Revolution Revolutionize Psychiatry? Am J Psychiatry, April 1, 2003; 160(4): 625 - 635. [Full Text] [PDF]
|
|
|
|
 |
|
 Contributions of Cholesterol, BP, and Genetics in Alzheimer's Disease Journal Watch Cardiology, November 1, 2002; 2002(1101): 6 - 6. [Full Text]
|
|
Article
