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APOE genotype and survival in men and women with Alzheimer’s disease

From the Departments of Neurology (Drs. Dal Forno, Carson, Troncoso, and Kawas) and Psychiatry and Behavioral Sciences (Dr. Brandt), the Neuropathology Laboratory, and the Department of Pathology (Dr. Troncoso), and the Alzheimer’s Disease Research Center (Drs. Dal Forno, Carson, Brookmeyer, Troncoso, Kawas, and Brandt), The Johns Hopkins University School of Medicine; and the Department of Biostatistics (Dr. Brookmeyer), The Johns Hopkins University School of Public Health, Baltimore, MD.

Address correspondence and reprint requests to Dr. Jason Brandt, Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Meyer 218, Baltimore, MD 21287-7218; e-mail: jbrandt{at}jhmi.edu

Background: The 4 allele of the APOE gene (APOE) is more frequent in patients with AD than in the general population, but studies are inconclusive as to whether it affects rate of progression or survival. Because survival in AD is generally longer in women than in men, the authors investigated whether APOE affects 10-year survival equally in men and women.

Methods: APOE testing was performed on 125 patients with probable AD enrolled in the Johns Hopkins AD Research Center between November 1984 and March 1987. The 39 men and 86 women were followed at 6-month intervals until censoring (by death or withdrawal from the study) or March 1997. Patients were dichotomized into those with and those without at least one 4 allele. For each sex, a Cox proportional hazards regression, allowing for delayed entry and covarying for age at onset, was used to examine the effect of 4 on survival.

Results: All patients who died during the study period and had autopsy (n = 92) were found to have definite AD. Average survival from disease onset did not differ by sex (12.1 years in men; 12.3 years in women). In neither sex were differences found between 4-positive and 4-negative subgroups in education, duration of AD at entry, or severity of dementia. However, in both sexes the 4-positive subgroup was approximately 3 years older at onset of AD and at entry to the study than the 4-negative subgroup. Adjusting for age at onset, the presence of an 4 allele significantly increased the relative risk of death only for men (RR = 2.69; 95% CI = 1.23 to 5.87).

Conclusions: In this sample of mostly white, well-educated research participants with AD, the APOE 4 allele was associated with shorter survival in men but not in women.

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