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Pre-eclampsia and risk of dementia later in life: nationwide cohort study

BMJ 2018; 363 doi: (Published 17 October 2018) Cite this as: BMJ 2018;363:k4109

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Pre-eclampsia and the brain

  1. Saima Basit, statistician,
  2. Jan Wohlfahrt, chief statistician,
  3. Heather A Boyd, senior researcher
  1. Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
  1. Correspondence to: H Boyd hoy{at}
  • Accepted 15 September 2018


Objective To explore associations between pre-eclampsia and later dementia, overall and by dementia subtype and timing of onset.

Design Nationwide register based cohort study.

Setting Denmark.

Population All women with at least one live birth or stillbirth between 1978 and 2015.

Main outcome measure Hazard ratios comparing dementia rates among women with and without a history of pre-eclampsia, estimated using Cox regression.

Results The cohort consisted of 1 178 005 women with 20 352 695 person years of follow-up. Women with a history of pre-eclampsia had more than three times the risk of vascular dementia (hazard ratio 3.46, 95% confidence interval 1.97 to 6.10) later in life, compared with women with no history of pre-eclampsia. The association with vascular dementia seemed to be stronger for late onset disease (hazard ratio 6.53, 2.82 to 15.1) than for early onset disease (2.32, 1.06 to 5.06) (P=0.08). Adjustment for diabetes, hypertension, and cardiovascular disease attenuated the hazard ratios only moderately; sensitivity analyses suggested that body mass index was unlikely to explain the association with vascular dementia. In contrast, only modest associations were observed for Alzheimer’s disease (hazard ratio 1.45, 1.05 to 1.99) and other/unspecified dementia (1.40, 1.08 to 1.83).

Conclusions Pre-eclampsia was associated with an increased risk of dementia, particularly vascular dementia. Cardiovascular disease, hypertension, and diabetes were unlikely to mediate the associations substantially, suggesting that pre-eclampsia and vascular dementia may share underlying mechanisms or susceptibility pathways. Asking about a history of pre-eclampsia could help physicians to identify women who might benefit from screening for early signs of disease, allowing for early clinical intervention.


  • Contributors: SB conceived and designed the study, acquired and analysed the data, interpreted the study findings, and drafted the manuscript. JW designed the study, advised on selection and implementation of analytical methods, interpreted the study findings, and critically reviewed the manuscript. HAB designed the study, supervised and directed the conduct of the study, interpreted the study findings, and critically revised the manuscript. All authors had full access to all of the data in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. HAB is the guarantor.

  • Funding: This work was supported by the Danish Council for Independent Research (DFF-4092-00213). The Danish Council for Independent Research had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. The researchers acted independently from the study sponsor in all aspects of this study.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at (available on request from the corresponding author) and declare: SB was supported by a grant from the Danish Council for Independent Research; 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: Studies based solely on data from the Danish national registers do not need approval from the Danish research bioethics committees, as study participants are never contacted, and consent is not required for the use of register information. The study’s use of register data was covered by the approval extended by the Danish Data Protection Agency to all register based studies conducted by Statens Serum Institut (approval No 2015-57-0102).

  • Data sharing: This study is based on Danish national register data. These data do not belong to the authors but to the Danish Ministry of Health, and the authors are not permitted to share them, except in aggregate (as, for example, in a publication). However, interested parties can obtain the data on which the study was based by submitting a research protocol to the Danish Data Protection Agency (Datatilsynet) and then, once permission has been received, applying to the Ministry of Health’s Research Service (Forskerservice) at

  • Transparency: The guarantor 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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