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Kristine Yaffe, MD; Jane Cauley, DrPH; Laura Sands, PhD; Warren Browner, MD, MPH

Arch Neurol. 1997;54(9):1110-1114.

Abstract
Objective
To determine whether apolipoprotein E (Apo E) phenotype is associated with cognitive decline in community-dwelling nondemented elderly

Design
Prospective cohort study.

Setting
A university-affiliated clinic near Pittsburgh, Pa.

Patients
A total of 1750 nondemented community-dwelling women, aged 65 years and older, who were enrolled in the Study of Osteoporotic Fractures.

Main Outcome Measures
The women completed a baseline interview and performed 3 cognitive tests: the modified Mini-Mental State Examination, Trails B, and Digit Symbol. Serum samples were obtained for Apo E typing. Baseline cognitive scores and repeated scores approximately 6 years after study enrollment were compared in women with and without Apo E 4. Cognitive decline, defined as the worst 10th percentile change scores, was assessed for each test and by phenotype group.

Results
After adjustment for age, education, presence of severe tremor, and depression, baseline scores did not differ by Apo E 4 status except for lower scores on Trails B in the homozygous 4 group (mean score, 159.7 compared with 127.7 for the heterozygous 4 group and 125.4 for the no 4 group; P=.01). However, repeated test performance on follow-up examination was worse on all tests in those women with 1 or more 4. Reduction on the modified Mini-Mental State Examination was 0% for no 4 allele, 1.9% for 1 4 allele, and 3.7% for 2 4 alleles (P<.001); reduction on Digit Symbol was 6.2% for no 4 allele, 9.0% for 1 4 allele, and 17.5% for 2 4 alleles (P=.04); and reduction on Trails B was 5.9% for no 4 allele, 25.0% for 1 4 allele, and 10.9% for 2 4 alleles (P=.002). Women with at least 1 4 had an odds ratio of 1.6 (95% confidence interval, 1.1-2.3) of having cognitive decline during the study period.

Conclusion
Apolipoprotein E 4 is associated with cognitive decline in community-dwelling nondemented women.

Author Affiliations
From the Departments of Psychiatry (Dr Yaffe), Medicine (Dr Browner), and Epidemiology and Biostatistics (Drs Yaffe and Browner), and Mt Zion Institute on Aging (Dr Sands), University of California, San Francisco; San Francisco Veterans Affairs Medical Center (Drs Yaffe and Browner); and Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pa (Dr Cauley).

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