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From the Wien Center for Alzheimer's Disease and Memory Disorders (Drs. Duara and Loewenstein, Mr. Barker, Lopez-Alberola, Gilchrist, and Ms. Grau), Mount Sinai Medical Center, Miami Beach, FL; Departments of Medicine and Neurology (Dr. Duara) and Psychiatry (Drs. Duara, Loewenstein, and Sevush), University of Miami School of Medicine, Miami, FL; and Division of Neurology, Departments of Medicine and Physiology (Dr. St. George-Hyslop), Center for Research in Neuro-degenerative Diseases, University of Toronto, Toronto, Canada.
Supported partially under an agreement with the Department of Elder Affairs of the State of Florida.
Received February 27, 1995. Accepted in final form October 18, 1995.
Address correspondence and reprint requests to Dr. Ranjan Duara, Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center; 4300 Alton Road; Miami Beach, FL 33140.
We evaluated 197 patients with predominantly late-onset Alzheimer's disease (AD) who belonged to several ethnic groups and analyzed the relationship of age of onset of AD to the presence or absence of several risk factors in this entire group of patients. The apolipoprotein E (apoE) epsilon 4 allele frequency, which was 29% in all patients (compared with the reported population mean of 13.7%, p < 0.001, did not vary significantly between ethnic groups but declined significantly with increasing age. The apoE epsilon 2 allele frequency was 3%, compared with the reported population mean of 7.4% (p = 0.001). The frequency of a positive family history of dementia in first-degree relatives (FH+) (overall 45%) did not vary significantly between ethnic groups. ApoE epsilon 4-positive (epsilon 4+) patients tended to have a higher FH+ rate (58%) than apoE epsilon 4-negative (epsilon 4-) patients (40%) (p = 0.02). When the potential risk factors of gender, education, FH+ status, and epsilon 4+ status were examined together in a multiple linear-regression analysis, FH+ and epsilon 4+ status (but not gender or education) were significant (they were both associated with an earlier age of onset of AD). In a post-hoc analysis, we found a reduced age of onset in women, but not men, who were both FH+ and epsilon 4+. Additionally, those probands who were epsilon 4+ were more likely to inherit the disease from their mothers than their fathers. The mechanism by which epsilon 4+ and FH+ status operate as risk factors may be by their effect on the age of onset of AD.
NEUROLOGY 1996;46: 1575-1579
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