Apolipoprotein E epsilon4 and incidence of Alzheimer disease in a community population of older persons

D. A. Evans, L. A. Beckett, T. S. Field, L. Feng, M. S. Albert, D. A. Bennett, B. Tycko and R. Mayeux
Rush Alzheimer's Disease Center, Chicago, IL 60612, USA.

OBJECTIVE: To examine the relation between apolipoprotein E status and risk of Alzheimer disease (AD) in a defined population and estimate the fraction of incident AD attributable to the epsilon4 allele. DESIGN: Community-based cohort study. SETTING: East Boston, Mass. PARTICIPANTS: A random sample of 578 community residents aged 65 years and older free of AD. MAIN OUTCOME MEASURE: Clinical diagnosis of AD by uniform, structured evaluation. RESULTS: The increased risk of AD associated with the presence of the epsilon4 allele was less than that found in most family and case-control studies. Persons with the epsilon4/epsilon4 or epsilon3/epsilon4 genotypes had 2.27 (95% confidence interval, 1.06-4.89) times the risk of incident disease compared with those with the epsilon3/epsilon3 genotype. The epsilon4 allele accounted for a fairly small fraction of the incidence of AD; if the allele did not exist or had no effect on disease risk, the incidence would be reduced by only 13.7%. The effect of the epsilon4 allele on risk of AD did not appear to vary with age. CONCLUSIONS: The apolipoprotein E epsilon4 allele is an important genetic risk factor for AD but accounts for a fairly small fraction of disease occurrence in this population-based study. Continued efforts to identify other environmental and genetic risk factors are warranted.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

The prevalence of dementia in the People's Republic of China: a systematic analysis of 1980 2004 studies
Dong et al.
Age Ageing 2007;36:619-624.
ABSTRACT | FULL TEXT  

Apolipoprotein E Gene and Age-Related Maculopathy in Older Individuals: The Cardiovascular Health Study
Tikellis et al.
Arch Ophthalmol 2007;125:68-73.
ABSTRACT | FULL TEXT  

Predictors of Cognitive Decline and Mortality of Aged People Over a 10-Year Period
Tilvis et al.
J. Gerontol. A Biol. Sci. Med. Sci. 2004;59:M268-M274.
ABSTRACT | FULL TEXT  

Apoe {epsilon}4 as a Predictor of Subjective Quality of Life in a Biracial Older Person Community Sample
Blazer et al.
J Aging Health 2003;15:645-660.
ABSTRACT  

Incidence of Alzheimer Disease in a Biracial Urban Community: Relation to Apolipoprotein E Allele Status
Evans et al.
Arch Neurol 2003;60:185-189.
ABSTRACT | FULL TEXT  

Apolipoprotein E {epsilon}4 allele, AD pathology, and the clinical expression of Alzheimer's disease
Bennett et al.
Neurology 2003;60:246-252.
ABSTRACT | FULL TEXT  

The apolipoprotein E {varepsilon}2 allele and decline in episodic memory
Wilson et al.
J. Neurol. Neurosurg. Psychiatry 2002;73:672-677.
ABSTRACT | FULL TEXT  

Midlife income, occupation, APOE status, and dementia: A population-based study
Anttila et al.
Neurology 2002;59:887-893.
ABSTRACT | FULL TEXT  

Depressive symptoms, cognitive decline, and risk of AD in older persons
Wilson et al.
Neurology 2002;59:364-370.
ABSTRACT | FULL TEXT  

The Apolipoprotein E {epsilon}4 Allele and Decline in Different Cognitive Systems During a 6-Year Period
Wilson et al.
Arch Neurol 2002;59:1154-1160.
ABSTRACT | FULL TEXT  

The APOE-E4 Allele and the Risk of Functional Decline in a Community Sample of African American and White Older Adults
Blazer et al.
J. Gerontol. A Biol. Sci. Med. Sci. 2001;56:M785-789.
ABSTRACT | FULL TEXT  

Association of Incident Alzheimer Disease and Blood Pressure Measured From 13 Years Before to 2 Years After Diagnosis in a Large Community Study
Morris et al.
Arch Neurol 2001;58:1640-1646.
ABSTRACT | FULL TEXT  

The complexities of predictive genetic testing
Evans et al.
BMJ 2001;322:1052-1056.
FULL TEXT  

Apolipoprotein E Genotypes and the Incidence of Alzheimer's Disease among Persons Aged 75 Years and Older: Variation by Use of Antihypertensive Medication?
Guo et al.
Am J Epidemiol 2001;153:225-231.
ABSTRACT | FULL TEXT  

Will Genetics Revolutionize Medicine?
Holtzman and Marteau
NEJM 2000;343:141-144.
FULL TEXT  

Apolipoprotein E Polymorphism and Alzheimer Disease: The Indo-US Cross-National Dementia Study
Ganguli et al.
Arch Neurol 2000;57:824-830.
ABSTRACT | FULL TEXT  

APOE-{epsilon}4 is associated with memory decline in cognitively impaired elderly
Dik et al.
Neurology 2000;54:1492-1497.
ABSTRACT | FULL TEXT  

APOE-{epsilon}4 predicts incident AD in Japanese-American men: The Honolulu-Asia Aging Study
Havlik et al.
Neurology 2000;54:1526-1529.
ABSTRACT | FULL TEXT  

Cognitive Function and Apolipoprotein E in Very Old Adults: Findings From the Nun Study
Riley et al.
J. Gerontol. B Psychol. Sci. Soc. Sci. 2000;55:69S-75.
ABSTRACT | FULL TEXT  

Incidence of Dementia in Relation to Stroke and the Apolipoprotein E {epsilon}4 Allele in the Very Old : Findings From a Population-Based Longitudinal Study
Zhu et al.
Stroke 2000;31:53-60.
ABSTRACT | FULL TEXT  

ApoE genotype in relation to AD and cholesterol: A study of 2,326 Chinese adults
Liu et al.
Neurology 1999;53:962-962.
ABSTRACT | FULL TEXT  

The Role of APOE{epsilon}4 in Modulating Effects of Other Risk Factors for Cognitive Decline in Elderly Persons
Haan et al.
JAMA 1999;282:40-46.
ABSTRACT | FULL TEXT  

Association Between Apolipoprotein E{epsilon}4 and the Rate of Cognitive Decline in Community-Dwelling Elderly Individuals With and Without Dementia
Jonker et al.
Arch Neurol 1998;55:1065-1069.
ABSTRACT | FULL TEXT  

The prevalence of apoE-epsilon 4 in Alzheimer's disease is age dependent
Frisoni et al.
J. Neurol. Neurosurg. Psychiatry 1998;65:103-106.
ABSTRACT | FULL TEXT  

Risk Estimates of Dementia by Apolipoprotein E Genotypes From a Population-Based Incidence Study: The Rotterdam Study
Slooter et al.
Arch Neurol 1998;55:964-968.
ABSTRACT | FULL TEXT  

Epidemiology of Dementia and Alzheimer's Disease
Hendrie
AJGP 1998;6:3S-18.
ABSTRACT | FULL TEXT  

A population study of apoE genotype at the age of 85: relation to dementia, cerebrovascular disease, and mortality
Skoog et al.
J. Neurol. Neurosurg. Psychiatry 1998;64:37-43.
ABSTRACT | FULL TEXT