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APOE ε4 and the Influence of Sex, Age, Vascular Risk Factors, and Ethnicity on Cognitive Decline

Makkar SR 1 , Lipnicki DM 1 , Crawford JD 1 , Kochan NA 1 , Castro-Costa E 2 , Lima-Costa MF 2 Show all authors , Diniz BS 3 , Brayne C 4 , Stephan B 5 , Matthews F 5 , Llibre-Rodriguez JJ 6 , Llibre-Guerra JJ 7 , Valhuerdi-Cepero AJ 8 , Lipton RB 9 , Katz MJ 9 , Wang C 9 , Ritchie K 10 , Carles S 11 , Carriere I 10 , Scarmeas N 12 , Yannakoulia M 13 , Kosmidis M 14 , Lam L 15 , Chan WC 15 , Fung A 16 , Guaita A 17 , Vaccaro R 17 , Davin A 17 , Kim KW 18 , Han JW 18 , Suh SW 18 , Riedel-Heller SG 19 , Roehr S 19 , Pabst A 19 , Ganguli M 20 , Hughes TF 21 , Snitz B 22 , Anstey KJ 23 , Cherbuin N 24 , Easteal S 25 , Haan MN 26 , Aiello AE 27 , Dang K 26 , Pin Ng T 28 , Gao Q 28 , Zin Nyunt MS 28 , Brodaty H 1 , Trollor JN 1 , Leung Y 29 , Lo JW 1 , Sachdev P 1

Affiliations 

  • 1 Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia
  • 2 Instituto René Rachou da Fundaçaõ Oswaldo Cruz, Rio de Janeiro, Brazil
  • 3 Department of Psychiatry, Faculty of Medicine University Toronto, Ontario, Canada
  • 4 Department of Public Health and Primary Care, Cambridge University, UK
  • 5 Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK
  • 6 Finlay-Albarrán Faculty of Medical Sciences, Medical University of Havana, Cuba
  • 7 Institute of Neurology and Neurosurgery, Havana, Cuba
  • 8 Medical University of Matanzas, Matanzas, Cuba
  • 9 Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, Yeshiva University, New York City, New York
  • 10 Inserm, U1061 Neuropsychiatry: Epidemiological and Clinical Research, La Colombière Hospital, Montpellier Cedex 5, France
  • 11 Inserm, UMR1153 Epidemiology and Biostatistics Sorbonne Paris Cité Center (CRESS), Paris, France
  • 12 1st Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens, Medical School, Athens, Greece
  • 13 Department of Nutrition and Dietetics (M.Y.), Harokopio University, Athens, Greece
  • 14 Laboratory of Cognitive Neuroscience, School of Psychology, Aristotle University of Thessaloniki, Thessaloniki, Greece
  • 15 Department of Psychiatry, The Chinese University of Hong Kong
  • 16 Department of Applied Social Sciences, The Hong Kong Polytechnic University
  • 17 Golgi Cenci Foundation, Abbiategrasso, Italy
  • 18 Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Korea
  • 19 Institute of Social Medicine, Occupational Health and Public Health (ISAP), Medical Faculty, University of Leipzig, Leipzig, Germany
  • 20 Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
  • 21 Department of Sociology, Anthropology, and Gerontology, Youngstown State University, Youngstown, Ohio
  • 22 Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
  • 23 Neuroscience Research Australia, Sydney, Australia
  • 24 Centre for Research on Ageing, Health and Wellbeing, College of Health and Medicine, The Australian National University, Canberra, Australia
  • 25 John Curtin School of Medical Research, College of Health and Medicine, The Australian National University, Canberra, Australia
  • 26 University of California, School of Medicine, Department of Epidemiology and Biostatistics, San Francisco, California
  • 27 Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, North Carolina
  • 28 Gerontology Research Programme, Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
  • 29 School of Psychology, University of Nottingham Malaysia, Semenyih, Malaysia
J Gerontol A Biol Sci Med Sci, 2020 09 25;75(10):1863-1873.
PMID: 32396611 DOI: 10.1093/gerona/glaa116

Abstract

We aimed to examine the relationship between Apolipoprotein E ε4 (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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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