Journal
JAMA NEUROLOGY
Volume 74, Issue 10, Pages 1178-1189Publisher
AMER MEDICAL ASSOC
DOI: 10.1001/jamaneurol.2017.2188
Keywords
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Categories
Funding
- Global Alzheimer's Association Interactive Network initiative of the Alzheimer's Association [GAAIN-14-244631]
- National Institutes of Health [U54-EB020406, P41-EB015922, R01-AG027161]
- Alzheimer's Disease Neuroimaging Initiative (National Institutes of Health) [U01 AG024904]
- Department of Defense Alzheimer's Disease Neuroimaging Initiative (Department of Defense) [W81XWH-12-2-0012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- AbbVie
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Araclon Biotech
- BioClinica, Inc
- Biogen
- Bristol-Myers Squibb Company
- CereSpir Inc
- Cogstate
- Eisai Inc
- Elan Pharmaceuticals Inc
- Eli Lilly and Company
- EuroImmun
- F. Hoffmann-La Roche Ltd
- Genentech Inc
- Fujirebio
- GE Healthcare
- IXICO Ltd
- Janssen Alzheimer Immunotherapy Research and Development LLC
- Johnson & Johnson Pharmaceutical Research & Development LLC
- Lumosity
- Lundbeck
- Merck and Co Inc
- Meso Scale Diagnostics LLC
- NeuroRx Research
- Neuro-track Technologies
- Novartis Pharmaceuticals Corporation
- Pfizer Inc
- Piramal Imaging
- Servier
- Takeda Pharmaceutical Company
- Transition Therapeutics
- Canadian Institutes of Health Research
- Commonwealth Scientific and Industrial Research Organization
- National Institute of Aging [U01 AG016976, P30 AG019610, P30 AG013846, P50 AG008702, P50 AG025688, P50 AG047266, P30 AG010133, P50 AG005146, P50 AG005134, P50 AG016574, P50 AG005138, P30 AG008051, P30 AG013854, P50 AG005131, P50 AG023501, P30 AG035982, P30 AG028383, P30 AG010124, P50 AG005133]
- National Institute on Aging Alzheimer's Disease Data Storage Site at the University of Pennsylvania - National Institute on Aging [U24-AG041689-01]
- Alzheimer's Association [IIRG09133827]
- BrightFocus Foundation [A2011048]
- Banner Alzheimer's Foundation
- Johnnie B. Byrd Sr Alzheimer's Institute
- Medical Research Council
- state of Arizona
- Higher Education Funding Council for England
- Alzheimer's Research Trust
- BRACE
- North Bristol National Health Services Trust Research and Innovation Department, The Netherlands
- StichtingMS Research
- Brain Net Europe
- Hersenstichting Nederland Breinbrekend Werk
- International Parkinson Fonds
- Internationale Stiching Alzheimer Onderzoek
- US Food and Drug Administration's Critical Path Public Private Partnerships Grant Program [1U18FD005320]
- European Commission [283562]
- Framingham Heart Study's National Heart, Lung, and Blood Institute [N01-HC-25195]
- National Institute of Neurological Disorders and Stroke [R01-NS017950]
- Accion Estrategica en Salud, Instituto de Salud Carlos III (ISCIII), Ministerio de Economia y Competitividad, Spain [PI13/02434]
- Fundacion Bancaria La Caixa (Barcelona, Spain)
- GRIFOLS SA and intramural funds
- Health Ageing Research Center, ChangGung University
- Center for Advanced Molecular Imaging and Translation, Chang Gung Memorial Hospital, Linkou
- National Center for Advancing Translational Science of the US National Institutes of Health [UL1TR001855, UL1TR000130]
- The National Institute of Ageing [P50 AG005681, P30 AG012300, P50 AG005136, P50 AG033514, P50 AG047270, U01AG032984, RC2AG036528, U24 AG21886, AG041232, R01-AG016495, R01-AG008122, R01-AG033040, P30 AG008017, P30 AG010161, P50 AG047366, P30 AG010129, P50 AG016573, P50 AG016570, P50 AG005142]
- [UO1 AG006781]
- [UO1 HG004610]
- [UO1 HG006375]
- [U01 HG008657]
- [P30AG10161]
- [R01AG15819]
- [R01AG17917]
- [U24 AG026395]
- [U24 AG026390]
- [R01AG041797]
- [R01AG09029]
- [R01AG025259]
- [R01 AG032990]
- [U01 AG046139]
- [R01 NS080820]
- [RF1 AG051504]
- [R01 AG027944]
- [R01 AG028786]
- [R01 AG019085]
- [P01 AG002219]
- [P01 AG03991]
- [P01 AG026276]
- [AG030653]
- [AG041718]
- [AG07562]
- [AG02365]
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IMPORTANCE It is unclear whether female carriers of the apolipoprotein E (APOE) epsilon 4 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. OBJECTIVE To determine how sex and APOE genotype affect the risks for developing MCI and AD. DATA SOURCES Twenty-seven independent research studies in the Global Alzheimer's Association Interactive Network with data on nearly 58 000 participants. STUDY SELECTION Non-Hispanic white individuals with clinical diagnostic and APOE genotype data. DATA EXTRACTION AND SYNTHESIS Homogeneous data setswere pooled in case-control analyses, and logistic regression models were used to compute risks. MAIN OUTCOMES AND MEASURES Age-adjusted odds ratios (ORs) and 95% confidence intervals for developing MCI and AD were calculated for men and women across APOE genotypes. RESULTS 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 epsilon 3/epsilon 4 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 epsilon 3/epsilon 4 had an increased risk of AD compared with men with APOE epsilon 3/epsilon 3. The APOE epsilon 2/epsilon 3 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 e3/e4 (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 epsilon 4/epsilon 4 showed increased risks vs individuals with epsilon 3/epsilon 4, but no significant differences between men and women with epsilon 4/epsilon 4 were seen. CONCLUSIONS AND RELEVANCE Contrary to long-standing views, men and women with the APOE epsilon 3/epsilon 4 genotype have nearly the same odds of developing AD from age 55 to 85 years, but women have an increased risk at younger ages. (C) 2017 American Medical Association. All rights reserved.
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