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Apolipoprotein E Genotype and Sex Risk Factors for Alzheimer Disease

Overview of attention for article published in JAMA Neurology, October 2017
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Title
Apolipoprotein E Genotype and Sex Risk Factors for Alzheimer Disease
Published in
JAMA Neurology, October 2017
DOI 10.1001/jamaneurol.2017.2188
Pubmed ID
Authors

Scott C. Neu, Judy Pa, Walter Kukull, Duane Beekly, Amanda Kuzma, Prabhakaran Gangadharan, Li-San Wang, Klaus Romero, Stephen P. Arneric, Alberto Redolfi, Daniele Orlandi, Giovanni B. Frisoni, Rhoda Au, Sherral Devine, Sanford Auerbach, Ana Espinosa, Mercè Boada, Agustín Ruiz, Sterling C. Johnson, Rebecca Koscik, Jiun-Jie Wang, Wen-Chuin Hsu, Yao-Liang Chen, Arthur W. Toga

Abstract

It is unclear whether female carriers of the apolipoprotein E (APOE) ε4 allele are at greater risk of developing Alzheimer disease (AD) than men, and the sex-dependent association of mild cognitive impairment (MCI) and APOE has not been established. To determine how sex and APOE genotype affect the risks for developing MCI and AD. Twenty-seven independent research studies in the Global Alzheimer's Association Interactive Network with data on nearly 58 000 participants. Non-Hispanic white individuals with clinical diagnostic and APOE genotype data. Homogeneous data sets were pooled in case-control analyses, and logistic regression models were used to compute risks. Age-adjusted odds ratios (ORs) and 95% confidence intervals for developing MCI and AD were calculated for men and women across APOE genotypes. Participants were men and women between ages 55 and 85 years. Across data sets most participants were white, and for many participants, racial/ethnic information was either not collected or not known. Men (OR, 3.09; 95% CI, 2.79-3.42) and women (OR, 3.31; CI, 3.03-3.61) with the APOE ε3/ε4 genotype from ages 55 to 85 years did not show a difference in AD risk; however, women had an increased risk compared with men between the ages of 65 and 75 years (women, OR, 4.37; 95% CI, 3.82-5.00; men, OR, 3.14; 95% CI, 2.68-3.67; P = .002). Men with APOE ε3/ε4 had an increased risk of AD compared with men with APOE ε3/ε3. The APOE ε2/ε3 genotype conferred a protective effect on women (OR, 0.51; 95% CI, 0.43-0.61) decreasing their risk of AD more (P value = .01) than men (OR, 0.71; 95% CI, 0.60-0.85). There was no difference between men with APOE ε3/ε4 (OR, 1.55; 95% CI, 1.36-1.76) and women (OR, 1.60; 95% CI, 1.43-1.81) in their risk of developing MCI between the ages of 55 and 85 years, but women had an increased risk between 55 and 70 years (women, OR, 1.43; 95% CI, 1.19-1.73; men, OR, 1.07; 95% CI, 0.87-1.30; P = .05). There were no significant differences between men and women in their risks for converting from MCI to AD between the ages of 55 and 85 years. Individuals with APOE ε4/ε4 showed increased risks vs individuals with ε3/ε4, but no significant differences between men and women with ε4/ε4 were seen. Contrary to long-standing views, men and women with the APOE ε3/ε4 genotype have nearly the same odds of developing AD from age 55 to 85 years, but women have an increased risk at younger ages.

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Geographical breakdown

Country Count As %
Unknown 116 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 27 23%
Student > Ph. D. Student 23 20%
Student > Master 15 13%
Other 11 9%
Student > Doctoral Student 10 9%
Other 30 26%
Readers by discipline Count As %
Medicine and Dentistry 23 20%
Unspecified 20 17%
Neuroscience 19 16%
Psychology 13 11%
Agricultural and Biological Sciences 12 10%
Other 29 25%