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Timing of onset of cognitive decline: results from Whitehall II prospective cohort study

BMJ 2012; 344 doi: (Published 05 January 2012) Cite this as: BMJ 2012;344:d7622
  1. Archana Singh-Manoux, research director123,
  2. Mika Kivimaki, professor of social epidemiology2,
  3. M Maria Glymour, assistant professor4,
  4. Alexis Elbaz, research director56,
  5. Claudine Berr, research director78,
  6. Klaus P Ebmeier, professor of old age psychiatry9,
  7. Jane E Ferrie, senior research fellow10,
  8. Aline Dugravot, statistician1
  1. 1Institut National de la Santé et de la Recherche Médicale (INSERM), U1018, Centre for Research in Epidemiology and Population Health, Hôpital Paul Brousse, 94807 Villejuif Cedex, France
  2. 2Department of Epidemiology and Public Health, University College London, London, UK
  3. 3Centre de Gérontologie, Hôpital Ste Périne, AP-HP, France
  4. 4Department of Society, Human Development, and Health, Harvard School of Public Health, Boston, MA, USA
  5. 5Institut National de la Santé et de la Recherche Médicale (INSERM), U708, F-75013, Paris, France
  6. 6UPMC Univ Paris 06, UMR_S 708, F-75005, Paris
  7. 7Institut National de la Santé et de la Recherche Médicale (INSERM) U1061 Université Montpellier 1, Montpellier, France
  8. 8CMRR Languedoc-Roussillon, CHU Montpellier
  9. 9Oxford University Department of Psychiatry, Warneford Hospital, Oxford, UK
  10. 10University of Bristol, Bristol, UK
  1. Correspondence to: A Singh-Manoux, INSERM, U1018, Centre for Research in Epidemiology and Population Health, Hôpital Paul Brousse, Bât 15/16, 16 Avenue Paul Vaillant Couturier, 94807 Villejuif Cedex, France Archana.Singh-Manoux{at}
  • Accepted 26 October 2011


Objectives To estimate 10 year decline in cognitive function from longitudinal data in a middle aged cohort and to examine whether age cohorts can be compared with cross sectional data to infer the effect of age on cognitive decline.

Design Prospective cohort study. At study inception in 1985-8, there were 10 308 participants, representing a recruitment rate of 73%.

Setting Civil service departments in London, United Kingdom.

Participants 5198 men and 2192 women, aged 45-70 at the beginning of cognitive testing in 1997-9.

Main outcome measure Tests of memory, reasoning, vocabulary, and phonemic and semantic fluency, assessed three times over 10 years.

Results All cognitive scores, except vocabulary, declined in all five age categories (age 45-49, 50-54, 55-59, 60-64, and 65-70 at baseline), with evidence of faster decline in older people. In men, the 10 year decline, shown as change/range of test×100, in reasoning was −3.6% (95% confidence interval −4.1% to −3.0%) in those aged 45-49 at baseline and −9.6% (−10.6% to −8.6%) in those aged 65-70. In women, the corresponding decline was −3.6% (−4.6% to −2.7%) and −7.4% (−9.1% to −5.7%). Comparisons of longitudinal and cross sectional effects of age suggest that the latter overestimate decline in women because of cohort differences in education. For example, in women aged 45-49 the longitudinal analysis showed reasoning to have declined by −3.6% (−4.5% to −2.8%) but the cross sectional effects suggested a decline of −11.4% (−14.0% to −8.9%).

Conclusions Cognitive decline is already evident in middle age (age 45-49).


  • We thank all the participating civil service departments and their welfare, personnel, and establishment officers; the British Occupational Health and Safety Agency; the British Council of Civil Service Unions; all participating civil servants in the Whitehall II study; and all members of the Whitehall II study team. The Whitehall II Study team comprises research scientists, statisticians, study coordinators, nurses, data managers, administrative assistants, and data entry staff, who make the study possible.

  • Contributors: AS-M wrote the first and successive drafts of the paper. AD carried out all the statistical analysis. All authors contributed to the interpretation of results and revision of the paper and approved the final version of the paper. AS-M is guarantor.

  • Funding: ASM is supported by a European Young Investigator Award from the European Science Foundation and the National Institute on Aging, NIH (R01AG013196 [PI]; R01AG034454 [PI]). MK is supported by the BUPA Foundation, the National Institutes of Health (R01HL036310 [PI]; R01AG034454 [PI]) and the Academy of Finland. The Whitehall II study is also supported by a grant from the British Medical Research Council (G0902037) and the British Heart Foundation. The funding bodies had no role in the study design, the collection, analysis and interpretation of data, the writing, and the decision to submit the paper.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: This study was approved by the University College London ethics committee, and all participants provided written consent.

  • Data sharing: Whitehall II data, protocols, and other metadata are available to the scientific community. Please refer to the Whitehall II data sharing policy at

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