Cited by 836Dementia and Cognitive Impairment ResearchCognitive Abilities and TestingAging and Gerontology Research

The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index; none of the 15 sources its claims cite is checked for support yet.

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

Open access
Singh-Manoux, A., Kivimaki, M., Glymour, M. M., Elbaz, A., Berr, C., Ebmeier, K. P., Ferrie, J. E., Dugravot, A.·2012·BMJ

Abstract

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).

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

In the Whitehall II prospective cohort, cognitive scores except vocabulary declined over 10 years in all age groups from 45–49 to 65–70, with faster decline at older ages. Cross-sectional age comparisons overestimated cognitive decline in women, probably because of cohort differences in education.

Key findings

  • All cognitive scores except vocabulary declined in all five baseline age categories (45–49, 50–54, 55–59, 60–64, 65–70), with evidence of faster decline in older people. In men, 10-year decline in reasoning was −3.6% (95% CI −4.1% to −3.0%) in those aged 45–49 and −9.6% (−10.6% to −8.6%) in those aged 65–70; in women, the corresponding declines were −3.6% (−4.6% to −2.7%) and −7.4% (−9.1% to −5.7%).
  • Longitudinal and cross-sectional estimates diverged, especially in women: in women aged 45–49, reasoning declined by −3.6% (−4.5% to −2.8%) longitudinally, but cross-sectional effects suggested a decline of −11.4% (−14.0% to −8.9%).
  • Adjustment for education did not change longitudinal estimates much but substantially reduced cross-sectional estimates of ageing, consistent with cohort differences in education. For women aged 45–49 at baseline, 34% had less than secondary school education, 28% secondary school, and 40% a university degree; for women aged 55–59, the corresponding figures were 58%, 25%, and 17%.
  • Vocabulary was little influenced by age; significant declines were seen for all tests except vocabulary in all age categories in both men and women.

Methods

  • Prospective cohort study using Whitehall II data; cognitive testing was introduced at phase 5 (1997–9) and repeated at phases 7 (2002–4) and 9 (2007–9). Analysis included 7390 participants (5198 men, 2192 women) aged 45–70 at baseline; 4675 (63%) had complete data at all three phases.
  • Cognitive battery included the Alice Heim 4-I reasoning test, a 20-word free recall memory test, phonemic and semantic fluency tests, and the Mill Hill vocabulary test. Results were expressed as percent change (change/range of test × 100).
  • Linear mixed models with random intercept and slope estimated 10-year decline, including age cohort × time interaction terms and stratification by sex; cross-sectional linear regression at baseline was compared with longitudinal estimates. Analyses used SAS Proc Mixed version 9.1.

Limitations

  • The paper states that longitudinal data can underestimate age effects because of practice effects and selective sample retention; non-response was higher in older individuals, though the overall response rate was 80% (7390/9250) among those invited to cognitive testing.
  • The paper states that Whitehall II is not representative of the general population: participants were mostly white collar workers in relatively stable employment and two thirds were men, so results could underestimate cognitive decline at the population level.
  • The paper notes that adjustment for education may not capture all cohort-related effects and may overcorrect by attributing shared variance between age and education to education. Evident from the text: cognitive testing began at age 45, so the study cannot determine whether decline begins before age 45.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1136/bmj.d7622

Cites

42 of 42 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

0 of 15 cited sources checked · 0 supported · 0 flagged

Show all 27 claims

  • It may state two separate claims as one. 12
  • Probably not a substantial claim. 15
24 of 24
  • The paper relies on this without support.

    Missing cognitive data are missing at random, so linear mixed models yield unbiased estimates.

    “Linear mixed models 21 were used to estimate cognitive decline over follow-up.This method uses all available data over follow-up, takes into account the fact that repeated measures on the same individual are correlated with each other, and can handle missing data.”
  • The paper relies on this without support.

    The cognitive tests are valid measures of cognitive function in this middle-aged population.

    “The cognitive test battery, administered at three clinical examinations over 10 years (phases 5, 7, and 9), was chosen to provide a comprehensive assessment of cognitive function and be appropriate for this population composed of individuals younger than in most studies on cognitive ageing.”
  • The paper relies on this without support.

    Cognitive decline over the 10-year follow-up is linear in time within each age cohort.

    “The models included terms for time (age in years, divided by 10 so the coefficients yield effects of decline over 10 years), age cohorts (age at baseline in five year bands) to adjust for secular effects, and an interaction term between age cohort and time, separately in men and women.”
3 of 3

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Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Two values given for reasoning decline in younger men

    Minor

    The results report a 10-year reasoning decline of -3.6% for men aged 45-49 at baseline, but the concluding summary reports -3.5% for the same group.

  • Conflicting secondary-school education percentage for younger women

    Minor

    The results state that 28% of women aged 45-49 had completed secondary school, while the table footnote gives 26% for the same group. The results' three education percentages for these women also total 102%.

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Metadata

Authors
Singh-Manoux, A., Kivimaki, M., Glymour, M. M., Elbaz, A., Berr, C., Ebmeier, K. P., Ferrie, J. E., & Dugravot, A.
Affiliations
  • Harvard University (US)
  • Inserm (FR)
  • Warneford Hospital (GB)
  • University of Bristol (GB)
Venue
BMJ
Publisher
BMJ
Published
2012-01-05
Volume
344
Issue
jan04 4
Pages
d7622-d7622
ISSN
  • 0007-1447 (ISSN-L)
  • 0959-8138
  • 1468-5833
OpenAlex
W2168922851
Cited by
836
References
41
Citations by year
2026: 45 · 2025: 39 · 2024: 66 · 2023: 67 · 2022: 52 · 2021: 81 · 2020: 70 · 2019: 64 · 2018: 44 · 2017: 54 · 2016: 51 · 2015: 45 · 2014: 52 · 2013: 55 · 2012: 46
FWCI
44.75
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • BMJ (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
  • HAL (submittedVersion, other-oa)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • British Heart Foundation (R01 AG013196, R01AG034454, RG/07/008/23674)
  • Bupa Foundation
  • European Science Foundation
  • Academy of Finland (R01 AG034454)
  • National Institutes of Health
  • Medical Research Council (R01AG034454, G0902037)
  • National Institute on Aging (R01AG034454, R01AG013196)
  • National Heart, Lung, and Blood Institute (R01HL036310)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
  • Social Sciences › Psychology › Developmental and Educational Psychology › Aging and Gerontology Research
Keywords
cognitive decline, cognitive aging, middle age (human life stage), age cohort effects, sex differences, reasoning, memory, vocabulary, fluency, Whitehall II cohort, public sector employees
MeSH terms
Adult, Aged, Aging, Cognition Disorders, Educational Status, Epidemiologic Methods, Female, Humans, London, Male, Middle Aged, Neuropsychological Tests, Age of Onset

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