Both women and men with the APOE ε3/ε4 genotype between the ages of 55 and 85 years have similar chances of receiving an Alzheimer disease (AD) diagnosis, according to findings from a meta-analysis published in JAMA Neurology.

Investigators evaluated 27 independent studies that featured a total of 31,340 non-Hispanic white men and women between the ages of 55 and 85 years. There was no difference between men and women with the APOE ε3/ε4 genotype with regard to AD risk.

A higher risk was observed among women between 65 years and 75 years of age compared with men (women: odds ratio [OR] 4.37; 95% CI, 3.82-5.00; men: OR 3.14; 95% CI, 2.68-3.67; P =.002). Men carrying the ε3/ε4 genotype had a greater AD risk compared with men with the APOE ε3/ε3 genotype (P <.001).

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For women, APOE ε2/ε3 was associated with a protective effect (OR 0.51; 95% CI, 0.43-0.61) and decreased their AD risk to a greater degree than men (OR 0.71; 95% CI, 0.60-0.85). The researchers also found that women had a greater risk for mild cognitive impairment developing between the ages of 55 and 70 compared with men (women: OR 1.43; 95% CI, 1.19-1.73; men: OR 1.07; 95% CI, 0.87-1.30; P =.05).

The researchers suggest that the variability in definitions for AD and mild cognitive impairment throughout the datasets may have had an impact on the study’s results. Additionally, the investigators were unable to adjust for AD risk factors such as family history of dementia.

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The investigators of this meta-analysis noted that the analyzed studies may have had ascertainment bias, and these biases “are known to modify the true effects of APOE on the risks of developing AD, and they may have played a role in the variations we found between data sets.”


Neu SC, Pa J, Kukull W, et al. Apolipoprotein E genotype and sex risk factors for Alzheimer disease: a meta-analysis [published online August 28, 2017]. JAMA Neurol. doi: 10.1001/jamaneurol.2017.2188