APOLIPOPROTEIN-E PHENOTYPE AND COGNITIVE DECLINE IN A PROSPECTIVE-STUDY OF ELDERLY COMMUNITY WOMEN

Objective: To determine whether apolipoprotein E (Ape E) phenotype is associated with cognitive decline in community-dwelling nondemented el derly women. Design: Prospective cohort study. Setting: A university-a ffiliated clinic near Pittsburgh, Pa. Patients: A total of 1750 nondem ented community-dwelling women, aged 65 years and older, who were enro lled in the Study of Osteoporotic Fractures. Main Outcome Measures: Th e women completed a baseline interview and performed 3 cognitive tests : the modified Mini-Mental State Examination, Trails B, and Digit Symb ol. Serum samples were obtained for Apo E typing. Baseline cognitive s cores and repeated scores approximately 6 years after study enrollment were compared in women with and without Apo E epsilon 4. Cognitive de cline, defined as the worst 10th percentile change scores, was assesse d for each test and by phenotype group. Results: After adjustment for age, education, presence of severe tremor, and depression, baseline sc ores did not differ by Apo E epsilon 4 status except for lower scores on Trails B in the homozygous epsilon 4 group (mean score, 159.7 compa red with 127.7 for the heterozygous epsilon 4 group and 125.4 for the no epsilon 4 group; P=.01). However, repeated test performance on foll ow-up examination was worse on all tests in those women with 1 or more epsilon 4. Reduction on the modified Mini-Mental State Examination wa s 0% for no epsilon 4 allele, 1.9% for 1 epsilon 4 allele, and 3.7% fo r 2 epsilon 4 alleles (P<.001); reduction on Digit Symbol was 6.2% for no epsilon 4 allele, 9.0% for 1 epsilon 4 allele, and 17.5% for 2 eps ilon 4 alleles (P=.04); and reduction on Trails B was 5.9% for no epsi lon 4 allele, 25.0% for 1 epsilon 4 allele, and 10.9% for 2 epsilon 4 alleles (P=.002). Women with at least 1 epsilon 4 had an odds ratio of 1.6 (95% confidence interval, 1.1-2.3) of having cognitive decline du ring the study period. Conclusion: Apolipoprotein E epsilon 4 is assoc iated with cognitive decline in community-dwelling nondemented women.