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Participants were 19,225 individuals aged 54\u2013103 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.<\/jats:p>","DOI":"10.1093\/gerona\/glaa116","type":"journal-article","created":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T20:23:40Z","timestamp":1589315020000},"page":"1863-1873","source":"Crossref","is-referenced-by-count":40,"title":["APOE \u03b54 and the Influence of Sex, Age, Vascular Risk Factors, and Ethnicity on Cognitive Decline"],"prefix":"10.1093","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2403-2472","authenticated-orcid":false,"given":"Steve R","family":"Makkar","sequence":"first","affiliation":[{"name":"Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren M","family":"Lipnicki","sequence":"additional","affiliation":[{"name":"Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D","family":"Crawford","sequence":"additional","affiliation":[{"name":"Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole A","family":"Kochan","sequence":"additional","affiliation":[{"name":"Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erico","family":"Castro-Costa","sequence":"additional","affiliation":[{"name":"Instituto Ren\u00e9 Rachou da Funda\u00e7a\u00f5 Oswaldo Cruz, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Fernanda","family":"Lima-Costa","sequence":"additional","affiliation":[{"name":"Instituto Ren\u00e9 Rachou da Funda\u00e7a\u00f5 Oswaldo Cruz, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Breno Satler","family":"Diniz","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine University Toronto, Ontario, Canada"},{"name":"Geriatric Psychiatry Division, Center for Addiction and Mental Health, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5307-663X","authenticated-orcid":false,"given":"Carol","family":"Brayne","sequence":"additional","affiliation":[{"name":"Department of Public Health and Primary Care, Cambridge University, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1235-360X","authenticated-orcid":false,"given":"Blossom","family":"Stephan","sequence":"additional","affiliation":[{"name":"Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Matthews","sequence":"additional","affiliation":[{"name":"Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan J","family":"Llibre-Rodriguez","sequence":"additional","affiliation":[{"name":"Finlay-Albarr\u00e1n Faculty of Medical Sciences, Medical University of Havana, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2137-7750","authenticated-orcid":false,"given":"Jorge J","family":"Llibre-Guerra","sequence":"additional","affiliation":[{"name":"Institute of Neurology and Neurosurgery, Havana, Cuba"},{"name":"Memory and Aging Center, UCSF, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adolfo J","family":"Valhuerdi-Cepero","sequence":"additional","affiliation":[{"name":"Medical University of Matanzas, Matanzas, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard B","family":"Lipton","sequence":"additional","affiliation":[{"name":"Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, Yeshiva University, New York City, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mindy J","family":"Katz","sequence":"additional","affiliation":[{"name":"Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, Yeshiva University, New York City, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuiling","family":"Wang","sequence":"additional","affiliation":[{"name":"Saul R. 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Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, The Chinese University of Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai Chi","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, The Chinese University of Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ada","family":"Fung","sequence":"additional","affiliation":[{"name":"Department of Applied Social Sciences, The Hong Kong Polytechnic University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Guaita","sequence":"additional","affiliation":[{"name":"Golgi Cenci Foundation, Abbiategrasso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Vaccaro","sequence":"additional","affiliation":[{"name":"Golgi Cenci Foundation, Abbiategrasso, 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Medicine, The Australian National University, Canberra, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Cherbuin","sequence":"additional","affiliation":[{"name":"Centre for Research on Ageing, Health and Wellbeing, College of Health and Medicine, The Australian National University, Canberra, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Easteal","sequence":"additional","affiliation":[{"name":"John Curtin School of Medical Research, College of Health and Medicine, The Australian National University, Canberra, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9312-4501","authenticated-orcid":false,"given":"Mary N","family":"Haan","sequence":"additional","affiliation":[{"name":"University of California, School of Medicine, Department of Epidemiology and Biostatistics, San Francisco, 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N","family":"Trollor","sequence":"additional","affiliation":[{"name":"Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia"},{"name":"Department of Developmental Disability Neuropsychiatry, School of Psychiatry, University of New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Leung","sequence":"additional","affiliation":[{"name":"School of Psychology, University of Nottingham Malaysia, Semenyih, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica W","family":"Lo","sequence":"additional","affiliation":[{"name":"Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9595-3220","authenticated-orcid":false,"given":"Perminder","family":"Sachdev","sequence":"additional","affiliation":[{"name":"Centre for Healthy Brain Ageing, University of New South 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