Apolipoprotein E epsilon4 allele, elevated midlife total cholesterol level, and high midlife systolic blood pressure are independent risk factors for late-life Alzheimer disease.
BACKGROUND
Presence of the apolipoprotein E (apoE) epsilon4 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.


OBJECTIVE
To study the relative importance and the putative relationship among the apoE epsilon4 allele, midlife total cholesterol level, and midlife blood pressure as risk factors for late-life Alzheimer disease.


METHODS
Prospective population-based study.


METHODS
Kuopio and Joensuu, eastern Finland.


METHODS
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).


METHODS
Midlife blood pressure and total cholesterol level, apoE genotype, and development of Alzheimer disease during follow-up.


RESULTS
The apoE epsilon4 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.


CONCLUSIONS
The association between the apoE epsilon4 allele and Alzheimer disease does not seem to be mediated by vascular factors. The apoE epsilon4 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 epsilon4 allele.
Kivipelto
Miia
M
University of Kuopio, Department of Neuroscience and Neurology, PO Box 1627, 70211 Kuopio, Finland. miia.kivipelto@uku.fi
Helkala
Eeva-Liisa
EL
Laakso
Mikko P
MP
Hänninen
Tuomo
T
Hallikainen
Merja
M
Alhainen
Kari
K
Iivonen
Susan
S
Mannermaa
Arto
A
Tuomilehto
Jaakko
J
Nissinen
Aulikki
A
Soininen
Hilkka
H
D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology*; D001057:Apolipoproteins E / Q000235:genetics*; D001794:Blood Pressure / Q000502:physiology*; D002784:Cholesterol / Q000097:blood*; D003704:Dementia / Q000175:diagnosis / Q000209:etiology; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D011446:Prospective Studies; D012044:Regression Analysis; D012307:Risk Factors
D001057:Apolipoproteins E; D002784:Cholesterol