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Am J Psychiatry 1997; 154:603-608
Copyright © 1997 by American Psychiatric Association
No association between apolipoprotein E epsilon 4 allele and rate of decline in Alzheimer's disease
GM Murphy Jr, J Taylor, HC Kraemer, J Yesavage and JR Tinklenberg
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, CA 94305-5485, USA. greer.murphy@forsythe.stanford.edu
OBJECTIVE: The relationship between number of apolipoprotein E epsilon 4
(APOE epsilon 4) alleles and the rate of cognitive decline in patients with
Alzheimer's disease was examined. METHOD: Rate of decline in score on the
Mini-Mental State was measured during the active phase of the decline curve
between Mini-Mental State scores of 23 and 0. To characterize onset, the
authors also estimated for each subject the age at which the Mini-Mental
State score fell below 23 and obtained a retrospective report of age at
onset from the caregiver. The number of APOE epsilon 4 alleles carried by
each subject was determined from genomic DNA samples. The study included 86
subjects with probable Alzheimer's disease who had had at least two
cognitive evaluations (a mean of 5.6 evaluations per subject over an
average period of 3.6 years). RESULTS: The results did not support an
association between APOE epsilon 4 dosage and rate of cognitive decline.
Age at onset and age at which the Mini-Mental State score fell below 23
were also not related to APOE epsilon 4 dosage. The APOE allele frequencies
were similar to those in other studies of subjects with Alzheimer's
disease, showing an enrichment of the epsilon 4 allele. CONCLUSIONS:
Although the APOE epsilon 4 allele is a risk factor for Alzheimer's
disease, there is no support of a strong association between APOE epsilon 4
dosage and rate of cognitive decline. The epsilon 4 allele did not predict
age at onset. Methodological inconsistencies may account for discrepancies
between these results and previous findings.
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