Education and the moderating roles of age, sex, ethnicity and apolipoprotein epsilon 4 on the risk of cognitive impairment

Steve R Makkar; Darren M Lipnicki; John D Crawford; Nicole A Kochan; Erico Castro-Costa; Maria Fernanda Lima-Costa; Breno Satler Diniz; Carol Brayne; Blossom Stephan; Fiona Matthews; Juan J Llibre-Rodriguez; Jorge J Llibre-Guerra; Adolfo J Valhuerdi-Cepero; Richard B Lipton; Mindy J Katz; Andrea Zammit; Karen Ritchie; Sophie Carles; Isabelle Carriere; Nikolaos Scarmeas; Mary Yannakoulia; Mary Kosmidis; Linda Lam; Ada Fung; Wai Chi Chan; Antonio Guaita; Roberta Vaccaro; Annalisa Davin; Ki Woong Kim; Ji Won Han; Seung Wan Suh; Steffi G Riedel-Heller; Susanne Roehr; Alexander Pabst; Mary Ganguli; Tiffany F Hughes; Erin P Jacobsen; Kaarin J Anstey; Nicolas Cherbuin; Mary N Haan; Allison E Aiello; Kristina Dang; Shuzo Kumagai; Kenji Narazaki; Sanmei Chen; Tze Pin Ng; Qi Gao; Ma Shwe Zin Nyunt; Kenichi Meguro; Satoshi Yamaguchi; Hiroshi Ishii; Antonio Lobo; Elena Lobo Escolar; Concepción De la Cámara; Henry Brodaty; Julian N Trollor; Yvonne Leung; Jessica W Lo; Perminder Sachdev; for Cohort Studies of Memory in an International Consortium (COSMIC)

doi:10.1016/j.archger.2020.104112

Education and the moderating roles of age, sex, ethnicity and apolipoprotein epsilon 4 on the risk of cognitive impairment

Arch Gerontol Geriatr. 2020 Nov/Dec:91:104112. doi: 10.1016/j.archger.2020.104112. Epub 2020 Jul 13.

Authors

Steve R Makkar¹, Darren M Lipnicki², John D Crawford², Nicole A Kochan², Erico Castro-Costa³, Maria Fernanda Lima-Costa³, Breno Satler Diniz⁴, Carol Brayne⁵, Blossom Stephan⁶, Fiona Matthews⁶, Juan J Llibre-Rodriguez⁷, Jorge J Llibre-Guerra⁸, Adolfo J Valhuerdi-Cepero⁹, Richard B Lipton¹⁰, Mindy J Katz¹¹, Andrea Zammit¹¹, Karen Ritchie¹², Sophie Carles¹³, Isabelle Carriere¹⁴, Nikolaos Scarmeas¹⁵, Mary Yannakoulia¹⁶, Mary Kosmidis¹⁷, Linda Lam¹⁸, Ada Fung¹⁹, Wai Chi Chan²⁰, Antonio Guaita²¹, Roberta Vaccaro²¹, Annalisa Davin²¹, Ki Woong Kim²², Ji Won Han²³, Seung Wan Suh²³, Steffi G Riedel-Heller²⁴, Susanne Roehr²⁴, Alexander Pabst²⁴, Mary Ganguli²⁵, Tiffany F Hughes²⁶, Erin P Jacobsen²⁵, Kaarin J Anstey²⁷, Nicolas Cherbuin²⁸, Mary N Haan²⁹, Allison E Aiello³⁰, Kristina Dang²⁹, Shuzo Kumagai³¹, Kenji Narazaki³², Sanmei Chen³³, Tze Pin Ng³⁴, Qi Gao³⁴, Ma Shwe Zin Nyunt³⁴, Kenichi Meguro³⁵, Satoshi Yamaguchi³⁵, Hiroshi Ishii³⁵, Antonio Lobo³⁶, Elena Lobo Escolar³⁶, Concepción De la Cámara³⁶, Henry Brodaty³⁷, Julian N Trollor³⁸, Yvonne Leung², Jessica W Lo², Perminder Sachdev³⁷; for Cohort Studies of Memory in an International Consortium (COSMIC)

Affiliations

¹ Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia. Electronic address: stevem@unsw.edu.au.
² Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia.
³ Instituto Rene´ Rachou da Fundaçaõ Oswaldo Cruz, Rio de Janeiro, Brazil.
⁴ Department of Psychiatry, Faculty of Medicine University, Toronto, Canada; Geriatric Psychiatry Division, Center for Addiction and Mental Health, Toronto, ON, Canada.
⁵ Department of Public Health and Primary Care, Cambridge University, UK.
⁶ Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK.
⁷ Finlay-Albarrán Faculty of Medical Sciences, Medical University of Havana, Cuba.
⁸ Institute of Neurology and Neurosurgery Havana, Cuba, Memory and Aging Center, UCSF San Francisco, United States.
⁹ Medical University of Matanzas, Cuba.
¹⁰ Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, Yeshiva University, New York City, NY, United States; Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Yeshiva University, New York City, NY, United States; Department of Psychiatry and Behavioral Medicine, Albert Einstein College of Medicine, Yeshiva University, New York City, NY, United States.
¹¹ Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, Yeshiva University, New York City, NY, United States.
¹² Inserm, U1061 Neuropsychiatry: Epidemiological and Clinical Research, La Colombière Hospital, Montpellier Cedex 5, France; Université de Montpellier, Montpellier, France; Centre for Clinical Brain Sciences, University of Edinburgh, UK.
¹³ Inserm, UMR1153 Epidemiology and Biostatistics Sorbonne Paris Cité Center (CRESS), Paris, F-75014 France; Paris Descartes University, Paris, France; Univ Paris-Sud, Villejuif, France.
¹⁴ Inserm, U1061 Neuropsychiatry: Epidemiological and Clinical Research, La Colombière Hospital, Montpellier Cedex 5, France; Université de Montpellier, Montpellier, France.
¹⁵ 1st Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens, Medical School, Athens, Greece; Taub Institute for Research in Alzheimer's Disease and the Aging Brain, Gertrude H Sergievsky Center, Department of Neurology, Columbia University, New York, NY, United States.
¹⁶ Department of Nutrition and Dietetics (M.Y.), Harokopio University, Athens, Greece.
¹⁷ Laboratory of Cognitive Neuroscience, School of Psychology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
¹⁸ Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong.
¹⁹ Department of Applied Social Sciences, The Hong Kong Polytechnic University, Hong Kong.
²⁰ Department of Psychiatry, The University of Hong Kong, Hong Kong.
²¹ Golgi Cenci Foundation, Corso San Martino 10, 20081 Abbiategrasso, Italy.
²² Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, South Korea; Department of Psychiatry, Seoul National University, College of Medicine, Seoul, South Korea; Department of Brain and Cognitive Science, Seoul National University College of Natural Sciences, Seoul, South Korea.
²³ Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, South Korea.
²⁴ Institute of Social Medicine, Occupational Health and Public Health (ISAP), Medical Faculty, University of Leipzig, Leipzig, Germany.
²⁵ Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
²⁶ Department of Sociology, Anthropology, and Gerontology, Youngstown State University, Youngstown, OH, United States.
²⁷ School of Psychology, University of New South Wales, Sydney, Australia; Neuroscience Research Australia, Sydney, Australia; Centre for Research on Ageing, Health and Wellbeing, College of Health and Medicine, The Australian National University, Canberra, Australia.
²⁸ Centre for Research on Ageing, Health and Wellbeing, College of Health and Medicine, The Australian National University, Canberra, Australia.
²⁹ University of California, School of Medicine, Department of Epidemiology and Biostatistics, CA, United States.
³⁰ Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill; Carolina Population Center, Chapel Hill, NC, United States.
³¹ Center for Health Science and Counseling, Kyushu University, 6-1 Kasuga kouen, Kasuga City, Fukuoka, 816-8580, Japan.
³² Faculty of Socio-Environmental Studies, Department of Socio-Environmental Studies, Fukuoka Institute of Technology, 3-30-1 Wajiro-higashi, Higashi-ku, Fukuoka 811-0295, Japan.
³³ Department of Epidemiology and Prevention, Center for Clinical Sciences, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjyuku-ku, Tokyo 162-8655, Japan.
³⁴ Gerontology Research Programme, Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
³⁵ Geriatric Behavioral Neurology, Tohoku University, Japan.
³⁶ Instituto de Investigación Sanitaria Aragón, Zaragoza, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Universidad de Zaragoza, Zaragoza, Spain.
³⁷ Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia; Dementia Collaborative Research Centre, University of New South Wales, Sydney, Australia.
³⁸ 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.

Abstract

Background: We examined how the relationship between education and latelife cognitive impairment (defined as a Mini Mental State Examination score below 24) is influenced by age, sex, ethnicity, and Apolipoprotein E epsilon 4 (APOE*4).

Methods: Participants were 30,785 dementia-free individuals aged 55-103 years, from 18 longitudinal cohort studies, with an average follow-up ranging between 2 and 10 years. Pooled hazard ratios were obtained from multilevel parametric survival analyses predicting cognitive impairment (CI) from education and its interactions with baseline age, sex, APOE*4 and ethnicity. In separate models, education was treated as continuous (years) and categorical, with participants assigned to one of four education completion levels: Incomplete Elementary; Elementary; Middle; and High School.

Results: Compared to Elementary, Middle (HR = 0.645, P = 0.004) and High School (HR = 0.472, P < 0.001) education were related to reduced CI risk. The decreased risk of CI associated with Middle education weakened with older baseline age (HR = 1.029, P = 0.056) and was stronger in women than men (HR = 1.309, P = 0.001). The association between High School and lowered CI risk, however, was not moderated by sex or baseline age, but was stronger in Asians than Whites (HR = 1.047, P = 0.044), and significant among Asian (HR = 0.34, P < 0.001) and Black (HR = 0.382, P = 0.016), but not White, APOE*4 carriers.

Conclusion: High School completion may reduce risk of CI associated with advancing age and APOE*4. The observed ethnoregional differences in this effect are potentially due to variations in social, economic, and political outcomes associated with educational attainment, in combination with neurobiological and genetic differences, and warrant further study.

Keywords: Age; Ageing; Cognitive decline; Education; Ethnicity; Sex.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Apolipoprotein E4 / genetics
Cognitive Dysfunction* / epidemiology
Cognitive Dysfunction* / genetics
Educational Status
Ethnicity*
Female
Humans
Longitudinal Studies
Male
Risk Factors

Substances

Apolipoprotein E4

Abstract

Publication types

MeSH terms

Substances

Grants and funding