APOE epsilon 4 and the Influence of Sex, Age, Vascular Risk Factors, and Ethnicity on Cognitive Decline

Centre for Healthy Brain Ageing. University of New South Wales. Sydney, Australia.
Centre for Healthy Brain Ageing. University of New South Wales. Sydney, Australia.
Centre for Healthy Brain Ageing. University of New South Wales. Sydney, Australia.
Centre for Healthy Brain Ageing. University of New South Wales. Sydney, Australia.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Department of Psychiatry. Faculty of Medicine University Toronto. Ontario, Canada/Geriatric Psychiatry Division. Center for Addiction and Mental Health. Toronto, Ontario, Canada.
Department of Public Health and Primary Care. Cambridge University, UK.
Institute of Health and Society. Newcastle University. Newcastle upon Tyne, UK.
Institute of Health and Society. Newcastle University. Newcastle upon Tyne, UK.
Finlay-Albarrán Faculty of Medical Sciences. Medical University of Havana. Cuba.
Institute of Neurology and Neurosurgery. Havana, Cuba/9 Memory and Aging Center. UCSF, San Francisco, California.
Medical University of Matanzas. Matanzas, Cuba.
Saul R. Korey Department of Neurology. Albert Einstein College of Medicine. Yeshiva University. New York City, New York.
Saul R. Korey Department of Neurology. Albert Einstein College of Medicine. Yeshiva University. New York City, New York.
Saul R. Korey Department of Neurology. Albert Einstein College of Medicine. Yeshiva University. New York City, New York.
Inserm. U1061 Neuropsychiatry: Epidemiological and Clinical Research. La Colombière Hospital. Montpellier Cedex 5, France/Université de Montpellier. Montpellier, France.
Inserm. UMR1153 Epidemiology and Biostatistics Sorbonne Paris Cité Center. Paris, France/Paris Descartes University. Paris, France.
Inserm. U1061 Neuropsychiatry: Epidemiological and Clinical Research. La Colombière Hospital. Montpellier Cedex 5, France/Université de Montpellier. Montpellier, France.
Paris Descartes University. Paris, France/1st Department of Neurology. Aiginition Hospital. National and Kapodistrian University of Athens. Medical School. Athens, Greece.
Department of Nutrition and Dietetics. Harokopio University. Athens, Greece.
Laboratory of Cognitive Neuroscience. School of Psychology. Aristotle University of Thessaloniki. Thessaloniki, Greece.
Department of Psychiatry. The Chinese University of Hong Kong. Hong Kong, China
Department of Psychiatry. The Chinese University of Hong Kong. Hong Kong, China
Department of Applied Social Sciences. The Hong Kong Polytechnic University.
Golgi Cenci Foundation. Abbiategrasso, Italy.
Golgi Cenci Foundation. Abbiategrasso, Italy.
Golgi Cenci Foundation. Abbiategrasso, Italy.
Department of Neuropsychiatry. Seoul National University Bundang Hospital. Seongnam, Korea/Department of Psychiatry. Seoul National University. College of Medicine. Seoul, Korea.
Department of Neuropsychiatry. Seoul National University Bundang Hospital. Seongnam, Korea.
Department of Neuropsychiatry. Seoul National University Bundang Hospital. Seongnam, Korea.
Institute of Social Medicine, Occupational Health and Public Health. Medical Faculty. University of Leipzig. Leipzig, Germany.
Institute of Social Medicine, Occupational Health and Public Health. Medical Faculty. University of Leipzig. Leipzig, Germany.
Institute of Social Medicine, Occupational Health and Public Health. Medical Faculty. University of Leipzig. Leipzig, Germany.
Department of Psychiatry. University of Pittsburgh School of Medicine. Pittsburgh, Pennsylvania.
Department of Sociology, Anthropology, and Gerontology. Youngstown State University, Youngstown, Ohio.
Department of Neurology. University of Pittsburgh School of Medicine. Pittsburgh, Pennsylvania.
Neuroscience Research Australia. Sydney, Australia/Centre for Research on Ageing. Health and Wellbeing. College of Health and Medicine. Australian National University, Canberra, Australia
Centre for Research on Ageing. Health and Wellbeing. College of Health and Medicine. Australian National University, Canberra, Australia.
John Curtin School of Medical Research. College of Health and Medicine. Australian National University. Canberra, Australia.
University of California. School of Medicine. Department of Epidemiology and Biostatistics. San Francisco, California.
Department of Epidemiology. Gillings School of Global Public Health. University of North Carolina. Chapel Hill, North Carolina/Carolina Population Center. Chapel Hill, North Carolina.
University of California. School of Medicine. Department of Epidemiology and Biostatistics. San Francisco, California.
Gerontology Research Programme. Department of Psychological Medicine. Yong Loo Lin School of Medicine., National University of Singapore. Singapore.
Gerontology Research Programme. Department of Psychological Medicine. Yong Loo Lin School of Medicine., National University of Singapore. Singapore.
Gerontology Research Programme. Department of Psychological Medicine. Yong Loo Lin School of Medicine., National University of Singapore. Singapore.
Centre for Healthy Brain Ageing. University of New South Wales. Sydney, Australia/Dementia Collaborative Research Centre. University of New South Wales Sydney. Sydney, Australia
Centre for Healthy Brain Ageing. University of New South Wales. Sydney, Australia/Department of Developmental Disability Neuropsychiatry. School of Psychiatry. University of New South Wales., Australia.
School of Psychology. University of Nottingham Malaysia. Semenyih, Malaysia.
Centre for Healthy Brain Ageing. University of New South Wales. Sydney, Australia.
Centre for Healthy Brain Ageing. University of New South Wales. Sydney, Australia/Dementia Collaborative Research Centre. University of New South Wales Sydney. Sydney, Australia

Abstract

We aimed to examine the relationship between Apolipoprotein E epsilon 4 (APOE*4) carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 individuals aged 54-103 years from 15 longitudinal cohort studies with a mean follow-up duration ranging between 1.2 and 10.7 years. Two-step individual participant data meta-analysis was used to pool results of study-wise analyses predicting memory and general cognitive decline from carriage of one or two APOE*4 alleles, and moderation of these associations by age, sex, vascular risk factors, and ethnicity. Separate pooled estimates were calculated in both men and women who were younger (ie, 62 years) and older (ie, 80 years) at baseline. Results showed that APOE*4 carriage was related to faster general cognitive decline in women, and faster memory decline in men. A stronger dose-dependent effect was observed in older men, with faster general cognitive and memory decline in those carrying two versus one APOE*4 allele. Vascular risk factors were related to an increased effect of APOE*4 on memory decline in younger women, but a weaker effect of APOE*4 on general cognitive decline in older men. The relationship between APOE*4 carriage and memory decline was larger in older-aged Asians than Whites. In sum, APOE*4 is related to cognitive decline in men and women, although these effects are enhanced by age and carriage of two APOE*4 alleles in men, a higher numbers of vascular risk factors during the early stages of late adulthood in women, and Asian ethnicity.

Keywords

Cognitive decline
APOE genotype
Epidemiology
Ethnicity
Sex

Publisher

Gerontological Society of America by Oxford University Press

Citation

MAKKAR, Steve R et al. APOE ε4 and the Influence of Sex, Age, Vascular Risk Factors, and Ethnicity on Cognitive Decline. J Gerontol A Biol Sci Med Sci., v. 75, n. 10, p. 1863-1873, 2020. doi: 10.1093/gerona/glaa116.

DOI

10.1093/gerona/glaa116

ISSN

1079-5006

Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/58580

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Copyright

Restricted access

Embargo date

2099-12-31

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