{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T10:24:05Z","timestamp":1784888645135,"version":"3.55.0"},"reference-count":43,"publisher":"BMJ","issue":"4","funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002283","name":"Alzheimer\u2019s Research UK","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002283","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2019,2,12]]},"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The life course determinants of midlife and later life cognitive function have been studied using longitudinal population-based cohort data, but far less is known about whether the pattern of these pathways is similar or distinct for clinically relevant cognitive state. We investigated this for Addenbrooke\u2019s Cognitive Examination third edition (ACE-III), used in clinical settings to screen for cognitive impairment and dementia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Longitudinal birth cohort study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Residential addresses in England, Wales and Scotland.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>1762 community-dwelling men and women of European heritage, enrolled since birth in the Medical Research Council (MRC) National Survey of Health and Development (the British 1946 birth cohort).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Primary outcome<\/jats:title>\n                    <jats:p>ACE-III.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Path modelling estimated direct and indirect associations between apolipoprotein E (\n                      <jats:italic>APOE<\/jats:italic>\n                      ) status, father\u2019s social class, childhood cognition, education, midlife occupational complexity, midlife verbal ability (National Adult Reading Test; NART), and the total ACE-III score. Controlling for sex, there was a direct negative association between\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 and the ACE-III score (\u03b2=\u22120.04 [\u20130.08 to \u20130.002], p=0.04), but not between\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 and childhood cognition (\u03b2=0.03 [\u20130.006 to 0.069], p=0.10) or the NART (\u03b2=0.0005 [\u20130.03 to 0.03], p=0.97). The strongest influences on the ACE-III were from childhood cognition (\u03b2=0.20 [0.14 to 0.26], p&lt;0.001) and the NART (\u03b2=0.35 [0.29 to 0.41], p&lt;0.001); educational attainment and occupational complexity were modestly and independently associated with the ACE-III (\u03b2=0.08 [0.03 to 0.14], p=0.002\u2009and \u03b2=0.05 [0.01 to 0.10], p=0.02, respectively).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The ACE-III in the general population shows a pattern of life course antecedents that is similar to neuropsychological measures of cognitive function, and may be used to represent normal cognitive ageing as well as a screen for cognitive impairment and dementia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2018-024404","type":"journal-article","created":{"date-parts":[[2019,4,25]],"date-time":"2019-04-25T06:06:45Z","timestamp":1556172405000},"page":"e024404","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":47,"title":["Identifying the lifetime cognitive and socioeconomic antecedents of cognitive state: seven decades of follow-up in a British birth cohort study"],"prefix":"10.1136","volume":"9","author":[{"given":"M","family":"Richards","sequence":"first","affiliation":[{"name":"MRC Unit for Lifelong Health and Ageing at UCL, UCL, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3800-4416","authenticated-orcid":false,"given":"Sarah-Naomi","family":"James","sequence":"additional","affiliation":[{"name":"MRC Unit for Lifelong Health and Ageing at UCL, UCL, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Sizer","sequence":"additional","affiliation":[{"name":"Epidemiology and Public Health, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikhil","family":"Sharma","sequence":"additional","affiliation":[{"name":"MRC Unit for Lifelong Health and Ageing at UCL, UCL, London, UK"},{"name":"National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Rawle","sequence":"additional","affiliation":[{"name":"MRC Unit for Lifelong Health and Ageing at UCL, UCL, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel H J","family":"Davis","sequence":"additional","affiliation":[{"name":"MRC Unit for Lifelong Health and Ageing at UCL, UCL, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7386-2857","authenticated-orcid":false,"given":"Diana","family":"Kuh","sequence":"additional","affiliation":[{"name":"MRC Unit for Lifelong Health and Ageing at UCL, UCL, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2019,4,24]]},"reference":[{"key":"2025121222225225000_9.4.e024404.1","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1007\/s10654-016-0217-8","article-title":"The MRC National Survey of Health and Development reaches age 70: maintaining participation at older ages in a birth cohort study","volume":"31","author":"Kuh","year":"2016","journal-title":"Eur J Epidemiol"},{"key":"2025121222225225000_9.4.e024404.2","doi-asserted-by":"publisher","DOI":"10.1076\/jcen.25.5.614.14581"},{"key":"2025121222225225000_9.4.e024404.3","doi-asserted-by":"crossref","DOI":"10.1038\/418932a","article-title":"Cognitive change and the APOE epsilon 4 allele","volume":"418","author":"Deary","year":"2002","journal-title":"Nature"},{"key":"2025121222225225000_9.4.e024404.4","doi-asserted-by":"publisher","DOI":"10.1159\/000351671"},{"key":"2025121222225225000_9.4.e024404.5","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2802"},{"key":"2025121222225225000_9.4.e024404.6","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/30.2.256"},{"key":"2025121222225225000_9.4.e024404.7","unstructured":"Pigeon DA . 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