This Article  • References  • Full text PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Social Bookmarking   What's this?

Apolipoprotein E 4 Allele and the Lifetime Risk of Alzheimer's Disease

What Physicians Know, and What They Should Know

Sudha Seshadri, MD; David A. Drachman, MD; Carol F. Lippa, MD

Arch Neurol. 1995;52(11):1074-1079.

Abstract
Background
Published studies now show a clear association between Alzheimer's disease (AD) and the apolipoprotein E 4 allele (APOE*4). The clinical value of this information to estimate a healthy individual's lifetime risk of AD has not been well delineated. Physicians dealing with AD may not know either the lifetime risk of developing AD or the effect of the APOE genotype on this risk. Because the lifetime risk of AD depends in part on life expectancy, and available figures on APOE are not population based, a computation is necessary to derive risk estimates useful to physicians.

Objectives
To estimate the lifetime risk of AD and the effect of APOE genotype information on that risk and to assess the knowledge of these risks among physicians who manage patients with dementia.

Design
Estimation of risk of AD and survey of physician awareness. The lifetime risk of developing AD without APOE genotype information was first computed for 65-year-olds from existing epidemiologic studies of age-related AD incidence and an actuarial life-table analysis. Using this computed a priori risk of AD and published studies of APOE genotypes in individuals with and without AD, we used a Bayesian analysis to determine the risk of developing AD, with and without an APOE*4 allele, for unaffected 65-year-olds. To assess physician knowledge of the lifetime risk of AD and the effect of APOE genotyping on the risk, 50 neurologists, internists, geriatricians, geriatric psychiatrists, and family physicians who manage patients with dementia were randomly selected to participate in a questionnaire-driven telephone survey.

Results
In a person with no family history of AD, the epidemiologic/actuarial lifetime risk of AD is approximately 15%. Based on a Bayesian calculation and published APOE data, the lifetime risk of AD is 29% for individuals with one APOE*4 allele and it is 9% if no APOE*4 allele is present. Physician awareness survey results were as follows: 42% of physicians correctly estimated the approximate lifetime risk of AD; of these, only one third were moderately sure of their response. Only three physicians correctly estimated the change in risk given the APOE*4 genotype; only one of these was at least moderately sure.

Conclusions
Determining the APOE*4 status of healthy adults with no family history of AD approximately doubles (for the 4 allele) or reduces by 40% (for the non-4 allele) the uninformed lifetime risk of developing AD. Even with anAPOE*4 allele, the lifetime risk remains below 30%. Most physicians managing patients with AD do not know the lifetime risk of AD, and very few know how APOE*4 status modifies the risk. These clinically relevant risk figures should be more widely disseminated among physicians.

Author Affiliations
From the Department of Neurology, University of Massachusetts Medical Center, Worcester.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Lipid homeostasis and apolipoprotein E in the development and progression of Alzheimer's disease
Lane and Farlow
J. Lipid Res. 2005;46:949-968.
ABSTRACT | FULL TEXT  

Cholesterol and apolipoprotein E in Alzheimer's disease
Reiss
AM J ALZHEIMERS DIS OTHER DEMEN 2005;20:91-96.
ABSTRACT  

Genetic aspects of Alzheimer's disease, Pick's disease, and other dementias
Nee et al.
AM J ALZHEIMERS DIS OTHER DEMEN 2004;19:219-225.
ABSTRACT  

Alzheimer's Disease and Parkinson's Disease
Nussbaum and Ellis
NEJM 2003;348:1356-1364.
FULL TEXT  

Alzheimer Disease
Cummings and Cole
JAMA 2002;287:2335-2338.
FULL TEXT  

Apolipoprotein E Polymorphism and Cardiovascular Disease: A HuGE Review
Eichner et al.
Am J Epidemiol 2002;155:487-495.
ABSTRACT | FULL TEXT  

Alzheimer's disease and other dementias: A review
Rogan and Lippa
AM J ALZHEIMERS DIS OTHER DEMEN 2002;17:11-17.
ABSTRACT  

Genetic risk of Alzheimer's disease: advising relatives
LIDDELL et al.
Br. J. Psychiatry 2001;178:7-11.
ABSTRACT | FULL TEXT  

Altered brain activation in cognitively intact individuals at high risk for Alzheimer's disease
Smith et al.
Neurology 1999;53:1391-1391.
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  

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  

Apolipoprotein E {epsilon}4 Allele and Familial Aggregation of Alzheimer Disease
Martinez et al.
Arch Neurol 1998;55:810-816.
ABSTRACT | FULL TEXT  

The new genetics: Genetic testing and public policy
Holtzman and Shapiro
BMJ 1998;316:852-856.
FULL TEXT  

Predictive Genetic Testing: From Basic Research to Clinical Practice
Holtzman et al.
Science 1997;278:602-605.
ABSTRACT | FULL TEXT  

Preparing Health Professionals for the Genetic Revolution
Collins
JAMA 1997;278:1285-1286.
ABSTRACT  

The Clinical Introduction of Genetic Testing for Alzheimer Disease: An Ethical Perspective
Post et al.
JAMA 1997;277:832-836.
ABSTRACT  

Neurology
Joynt
JAMA 1996;275:1826-1827.
ABSTRACT  

When a Mind Dies
Campion
NEJM 1996;334:791-792.
FULL TEXT