APOLIPOPROTEIN-E EPSILON-4 ALLELE AND THE LIFETIME RISK OF ALZHEIMERS-DISEASE - WHAT PHYSICIANS KNOW, ANN WHAT THEY SHOULD KNOW

Background: Published studies now show a clear association between Alz heimer's disease (AD) and the apolipoprotein E epsilon 4 allele (APOE epsilon 4). The clinical value of this information to estimate a healt hy individual's lifetime risk of AD has not been well delineated, Phys icians dealing with AD may not know either the lifetime risk of develo ping AD or the effect of the APOE genotype on this risk. Because the l ifetime risk of AD depends in part on life expectancy, and available f igures on APOE are not population based, a computation is necessary to derive risk estimates useful to physicians. Objectives: To estimate t he 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 an d survey of physician awareness. The lifetime risk of developing AD wi thout APOE genotype information was first computed for 65-year-olds fr om existing epidemiologic studies of age-related AD incidence and an a ctuarial life-table analysis. Using this computed a priori risk of AD and published studies of APOE genotypes in individuals with and withou t AD, we used a Bayesian analysis to determine the risk of developing AD, with and without an APOEepsilon 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, g eriatricians, geriatric psychiatrists, and family physicians who manag e patients with dementia were randomly selected to participate in a qu estionnaire-driven telephone survey. Results: In a person with no fami ly history of AD, the epidemiologic/actuarial lifetime risk of AD is a pproximately 15%. Based on a Bayesian calculation and published APOE d ata, the lifetime risk of AD is 29% for individuals with one APOEepsi lon 4 allele and it is 9% if no APOEepsilon 4 allele is present. Phys ician awareness survey results were as follows: 42% of physicians corr ectly estimated the approximate lifetime risk of AD; of these, only on e third were moderately sure of their response. Only three physicians correctly estimated the change in risk given the APOEepsilon 4 genoty pe; only one of these was at least moderately sure. Conclusions: Deter mining the APOEepsilon 4 status of healthy adults with no family hist ory of AD approximately doubles (for the epsilon 4 allele) or reduces by 40% (for the non-epsilon 4 allele) the uninformed lifetime risk of developing AD. Even with an APOEepsilon 4 allele, the lifetime risk r emains below 30%. Most physicians managing patients with AD do not kno w the lifetime risk of AD, and very few know how APOEepsilon 4 status modifies the risk. These clinically relevant risk figures should be m ore widely disseminated among physicians.