APOLIPOPROTEIN-E GENOTYPE DETERMINES SURVIVAL IN THE OLDEST-OLD (85 YEARS OR OLDER) WHO HAVE GOOD COGNITION

Objective: To quantify the influence of apolipoprotein E (APOE) polymo rphism on cognition and survival in a population sample aged 75 years or older. Design: The Kungsholmen Project established a cohort of 1810 residents in a district in Stockholm, Sweden, aged 75 years or older in 1987. Information on cognition at cohort inception is available for all subjects. Subjects were followed up for mortality to January 1, 1 995. Subjects: Included in this study are 1077 subjects (of 1124 genot yped for APOE) with the common epsilon 2/3, epsilon 3/3, and epsilon 3 /4 APOE genotypes. Results: The odds of cognitive impairment for the e psilon 3/4 vs epsilon 3/3 genotype declined with age: 4.8 for age 75 t hrough 79 years; 1.7 for age 80 through 84 years; and 1.0 (ie, no asso ciation) for age 85 years or older. Despite this association, APOE pol ymorphism did not significantly predict survival in subjects younger t han 85 years, nor did it predict survival in subjects 85 years or olde r who were cognitively impaired. Instead, survival varied fourfold wit h respect to APOE polymorphism in those 85 years or older who had good cognition: Mortality in subjects with the epsilon 2/3 genotype was ha lf that in those who carried the epsilon 3/3 genotype (hazard ratio, 0 .5; 95% confidence interval, 0.2 to 0.9), and mortality in subjects wi th the epsilon 3/4 genotype was twice that in those who carried the ep silon 3/3 genotype (hazard ratio, 2.0; 95% confidence interval, 1.1 to 3.5). This fourfold variation resulted in 2-year differences in survi val. Conclusions: The minor sequence variation in the apolipoprotein E isoforms resulted in a fourfold difference in the risk of death among the oldest old (age greater than or equal to 85 years) with good cogn ition. The observed variation in mortality was unlikely to have been c aused by cognitive impairment, as APOE polymorphism was not a risk fac tor for cognitive impairment in this age group.