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Association between major surgical admissions and the cognitive trajectory: 19 year follow-up of Whitehall II cohort study

BMJ 2019; 366 doi: (Published 07 August 2019) Cite this as: BMJ 2019;366:l4466

Linked editorial

The determinants of cognitive decline and dementia

  1. Bryan M Krause, biostatistician1,
  2. Séverine Sabia, research associate23,
  3. Helen J Manning, fellow4,
  4. Archana Singh-Manoux, professor23,
  5. Robert D Sanders, assistant professor1
  1. 1Department of Anesthesiology, University of Wisconsin, Madison, WI 53792-3272, USA
  2. 2Inserm U1153, Epidemiology of Ageing and Neurodegenerative diseases, Université de Paris, France
  3. 3Department of Epidemiology and Public Health, University College London, London, UK
  4. 4Department of Obstetrics and Gynecology, University of Wisconsin, Madison, WI, USA
  1. Correspondence to: R D Sanders robert.sanders{at}
  • Accepted 20 June 2019


Objective To quantify the association between major surgery and the age related cognitive trajectory.

Design Prospective longitudinal cohort study.

Setting United Kingdom.

Participants 7532 adults with as many as five cognitive assessments between 1997 and 2016 in the Whitehall II study, with linkage to hospital episode statistics. Exposures of interest included any major hospital admission, defined as requiring more than one overnight stay during follow-up.

Main outcomes measures The primary outcome was the global cognitive score established from a battery of cognitive tests encompassing reasoning, memory, and phonemic and semantic fluency. Bayesian linear mixed effects models were used to calculate the change in the age related cognitive trajectory after hospital admission. The odds of substantial cognitive decline induced by surgery defined as more than 1.96 standard deviations from a predicted trajectory (based on the first three cognitive waves of data) was also calculated.

Results After accounting for the age related cognitive trajectory, major surgery was associated with a small additional cognitive decline, equivalent on average to less than five months of aging (95% credible interval 0.01 to 0.73 years). In comparison, admissions for medical conditions and stroke were associated with 1.4 (1.0 to 1.8) and 13 (9.6 to 16) years of aging, respectively. Substantial cognitive decline occurred in 2.5% of participants with no admissions, 5.5% of surgical admissions, and 12.7% of medical admissions. Compared with participants with no major hospital admissions, those with surgical or medical events were more likely to have substantial decline from their predicted trajectory (surgical admissions odds ratio 2.3, 95% credible interval 1.4 to 3.9; medical admissions 6.2, 3.4 to 11.0).

Conclusions Major surgery is associated with a small, long term change in the average cognitive trajectory that is less profound than for major medical admissions. The odds of substantial cognitive decline after surgery was about doubled, though lower than for medical admissions. During informed consent, this information should be weighed against the potential health benefits of surgery.


  • Contributors: RDS and ASM conceived the study. BMK, SS, HJM, ASM, and RDS designed the study. BMK analyzed the data with input from RDS, SS, HJM, and ASM. BMK and RDS wrote the paper with input from all authors. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. BMK and RDS act as guarantors.

  • Funding: RDS is supported by US National Institutes of Health (K23 AG055700). The Whitehall II study is supported by grants from the US National Institutes of Health (R01AG056477), UK Medical Research Council (MRC K013351, MR/R024227), and British Heart Foundation (RG/13/2/30098). The funder played no role in these analyses.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at 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 University College London Hospital Committee on the Ethics of Human Research (reference No 85/0938), and University of Wisconsin, Madison, USA institutional review board (IRB No 2018-0658).

  • Data sharing: Data are publicly available through application for access to the Whitehall II database.

  • Transparency: The lead authors (BMK and RDS) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

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