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      Apolipoprotein-ε 4 is associated with higher fecundity in a natural fertility population

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          Abstract

          In many populations, the a polipoprotein-ε 4 ( APOE-ε 4) allele increases the risk for several chronic diseases of aging, including dementia and cardiovascular disease; despite these harmful effects at later ages, the APOE-ε 4 allele remains prevalent. We assess the impact of APOE-ε 4 on fertility and its proximate determinants (age at first reproduction, interbirth interval) among the Tsimane, a natural fertility population of forager-horticulturalists. Among 795 women aged 13 to 90 (20% APOE-ε 4 carriers), those with at least one APOE-ε 4 allele had 0.3 to 0.5 more children than (ε3/ε3) homozygotes, while those with two APOE-ε 4 alleles gave birth to 1.4 to 2.1 more children. APOE-ε 4 carriers achieve higher fertility by beginning reproduction 0.8 years earlier and having a 0.23-year shorter interbirth interval. Our findings add to a growing body of literature suggesting a need for studies of populations living in ancestrally relevant environments to assess how alleles that are deleterious in sedentary urban environments may have been maintained by selection throughout human evolutionary history.

          Abstract

          Among natural fertility forager-farmers, women with the APOE-ɛ 4 allele have more children, and the effect is dose dependent.

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          Most cited references71

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          2021 Alzheimer's disease facts and figures

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          This article describes the public health impact of Alzheimer's disease (AD), including incidence and prevalence, mortality and morbidity, use and costs of care, and the overall impact on caregivers and society. The Special Report discusses the challenges of providing equitable health care for people with dementia in the United States. An estimated 6.2 million Americans age 65 and older are living with Alzheimer's dementia today. This number could grow to 13.8 million by 2060 barring the development of medical breakthroughs to prevent, slow or cure AD. Official death certificates recorded 121,499 deaths from AD in 2019, the latest year for which data are available, making Alzheimer's the sixth-leading cause of death in the United States and the fifth-leading cause of death among Americans age 65 and older. Between 2000 and 2019, deaths from stroke, heart disease and HIV decreased, whereas reported deaths from AD increased more than 145%. This trajectory of deaths from AD was likely exacerbated in 2020 by the COVID-19 pandemic. More than 11 million family members and other unpaid caregivers provided an estimated 15.3 billion hours of care to people with Alzheimer's or other dementias in 2020. These figures reflect a decline in the number of caregivers compared with a decade earlier, as well as an increase in the amount of care provided by each remaining caregiver. Unpaid dementia caregiving was valued at $256.7 billion in 2020. Its costs, however, extend to family caregivers' increased risk for emotional distress and negative mental and physical health outcomes - costs that have been aggravated by COVID-19. Average per-person Medicare payments for services to beneficiaries age 65 and older with AD or other dementias are more than three times as great as payments for beneficiaries without these conditions, and Medicaid payments are more than 23 times as great. Total payments in 2021 for health care, long-term care and hospice services for people age 65 and older with dementia are estimated to be $355 billion. Despite years of efforts to make health care more equitable in the United States, racial and ethnic disparities remain - both in terms of health disparities, which involve differences in the burden of illness, and health care disparities, which involve differences in the ability to use health care services. Blacks, Hispanics, Asian Americans and Native Americans continue to have a higher burden of illness and lower access to health care compared with Whites. Such disparities, which have become more apparent during COVID-19, extend to dementia care. Surveys commissioned by the Alzheimer's Association recently shed new light on the role of discrimination in dementia care, the varying levels of trust between racial and ethnic groups in medical research, and the differences between groups in their levels of concern about and awareness of Alzheimer's disease. These findings emphasize the need to increase racial and ethnic diversity in both the dementia care workforce and in Alzheimer's clinical trials.
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            Pleiotropy, Natural Selection, and the Evolution of Senescence

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              Evolution in age-structured populations

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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing - original draftRole: Writing - review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: VisualizationRole: Writing - review & editing
                Role: Data curationRole: Formal analysisRole: MethodologyRole: ValidationRole: Writing - review & editing
                Role: ConceptualizationRole: InvestigationRole: Project administrationRole: Resources
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: ValidationRole: Writing - original draft
                Role: Data curationRole: Funding acquisitionRole: InvestigationRole: Project administrationRole: SupervisionRole: Writing - review & editing
                Role: Writing - review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: Writing - original draft
                Role: Writing - original draftRole: Writing - review & editing
                Role: ConceptualizationRole: Data curationRole: Writing - review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SoftwareRole: SupervisionRole: ValidationRole: Visualization
                Role: Formal analysisRole: MethodologyRole: SoftwareRole: ValidationRole: Visualization
                Role: InvestigationRole: MethodologyRole: Project administration
                Role: ConceptualizationRole: SupervisionRole: Writing - review & editing
                Role: Funding acquisitionRole: Writing - review & editing
                Role: Funding acquisitionRole: InvestigationRole: Project administrationRole: SupervisionRole: Writing - review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: Writing - original draftRole: Writing - review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: Writing - original draftRole: Writing - review & editing
                Journal
                Sci Adv
                Sci Adv
                sciadv
                advances
                Science Advances
                American Association for the Advancement of Science
                2375-2548
                August 2023
                09 August 2023
                : 9
                : 32
                : eade9797
                Affiliations
                [ 1 ]School of Human Evolution and Social Change, Arizona State University, Tempe, AZ, USA.
                [ 2 ]Center for Evolution and Medicine, Arizona State University, Tempe, AZ, USA.
                [ 3 ]Department of Population Health, New York University Grossman School of Medicine, New York City, NY, USA.
                [ 4 ]Anthropology Department, University of Utah, Salt Lake City, UT, USA.
                [ 5 ]Scientific Research Core, Phoenix Children's Hospital, Phoenix, AZ, USA.
                [ 6 ]Department of Child Health, University of Arizona, Tucson, AZ, USA.
                [ 7 ]Department of Health Economics and Anthropology, Economic Science Institute, Argyros School of Business and Economics, Chapman University, Orange, CA, USA.
                [ 8 ]Child and Brain Development Program, Canadian Institute for Advanced Research, Toronto, Ontario, Canada.
                [ 9 ]Department of Biological Sciences, Vanderbilt University, Nashville, TN, USA.
                [ 10 ]Universidad de San Simon, Cochabamba, Bolivia.
                [ 11 ]School of Life Sciences, Arizona State University, Tempe, AZ, USA.
                [ 12 ]Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
                [ 13 ]Tsimane Gran Consejo, San Borja, Bolivia.
                [ 14 ]MemorialCare Health System, Fountain Valley, CA, USA.
                [ 15 ]University of California, Irvine, CA, USA.
                [ 16 ]Center for Economic and Social Research, University of Southern California, Los Angeles, CA, USA.
                [ 17 ]Institute for Advanced Study in Toulouse, Université Toulouse 1 Capitole, Toulouse, France.
                [ 18 ]Leonard Davis School of Gerontology and Dornsife College, University of Southern California, Los Angeles, CA, USA.
                [ 19 ]Department of Anthropology, University of California Santa Barbara, Santa Barbara, CA, USA.
                Author notes
                Author information
                https://orcid.org/0000-0003-3201-0628
                https://orcid.org/0000-0001-9918-3617
                https://orcid.org/0000-0002-0634-9233
                https://orcid.org/0000-0001-7370-3020
                https://orcid.org/0000-0002-4673-7513
                https://orcid.org/0000-0002-8827-2750
                https://orcid.org/0000-0001-8145-0967
                https://orcid.org/0000-0001-5502-2790
                https://orcid.org/0000-0003-4653-3155
                https://orcid.org/0000-0002-4614-1859
                https://orcid.org/0000-0002-1071-9970
                https://orcid.org/0000-0001-5985-9643
                https://orcid.org/0000-0002-7617-3958
                https://orcid.org/0000-0002-7398-7358
                https://orcid.org/0000-0002-5661-527X
                Article
                ade9797
                10.1126/sciadv.ade9797
                10411886
                026829e2-bc90-4f1b-9d4f-271720e2e37c
                Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).

                This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 September 2022
                : 11 July 2023
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000001, National Science Foundation;
                Award ID: 1748282
                Funded by: FundRef http://dx.doi.org/10.13039/100000049, National Institute on Aging;
                Award ID: RF1AG054442
                Funded by: FundRef http://dx.doi.org/10.13039/100012736, Institute on Aging, College of Medicine, University of Florida;
                Award ID: RF1AG054442
                Funded by: FundRef http://dx.doi.org/10.13039/501100001665, Agence Nationale de la Recherche;
                Award ID: ANR-17-EURE-0010
                Categories
                Research Article
                Social and Interdisciplinary Sciences
                SciAdv r-articles
                Anthropology
                Anthropology
                Custom metadata
                Michael Sabado

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