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Apolipoprotein E ε4 Allele, Elevated Midlife Total Cholesterol Level, and High Midlife Systolic Blood Pressure Are Independent Risk Factors for Late-Life Alzheimer Disease

Miia Kivipelto, MD; Eeva-Liisa Helkala, PhD; Mikko P. Laakso, MD, PhD; Tuomo Hänninen, PhD; Merja Hallikainen, MD, PhD; Kari Alhainen, MD, PhD; Susan Iivonen, MS; Arto Mannermaa, PhD; Jaakko Tuomilehto, MD, PhD; Aulikki Nissinen, MD, PhD; and Hilkka Soininen, MD, PhD
[+] Article and Author 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@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.


Ann Intern Med. 2002;137(3):149-155. doi:10.7326/0003-4819-137-3-200208060-00006
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In our study, the association between the apoE ε4 allele and Alzheimer disease was not altered after adjustment for midlife total cholesterol level, midlife blood pressure, and late-life vascular disease. Similarly, the association of elevated midlife total cholesterol level and systolic blood pressure with late-life Alzheimer disease was not altered after adjustment for the apoE ε4 allele. These findings indicate that the apoE ε4 allele, high serum value for total cholesterol at midlife, and high systolic blood pressure at midlife are all independent risk factors for late-life Alzheimer disease. The risk was particularly high in participants who had all three risk factors. Furthermore, a history of myocardial infarction as of the late-life visit, which can typically result from having elevated total cholesterol level and high blood pressure, was associated with the risk for Alzheimer disease independent of the apoE ε4 allele.

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