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Mental health
Original research
Vascular and metabolic risk factor differences prior to dementia diagnosis: a multidatabase case–control study using European electronic health records
  1. Gayan Perera1,
  2. P R Rijnbeek2,
  3. Myriam Alexander3,
  4. David Ansell4,
  5. Paul Avillach5,6,
  6. Talita Duarte-Salles7,
  7. Mark Forrest Gordon8,
  8. Francesco Lapi9,
  9. Miguel Angel Mayer10,
  10. Alessandro Pasqua9,
  11. Lars Pedersen11,
  12. Johan van Der Lei2,
  13. Pieter Jelle Visser12,13,14,
  14. Robert Stewart1,15
  1. 1Psychological Medicine, King's College London (Institute of Psychiatry, Psychology and Neuroscience), London, UK
  2. 2Department of Medical Informatics, Erasmus Medical Center, Rotterdam, The Netherlands
  3. 3Quantitative Sciences, GlaxoSmithKline Plc, Brentford, UK
  4. 4Institute of Applied Health Research, University of Birmingham, Birmingham, UK
  5. 5Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, USA
  6. 6Aarhus University, Aarhus, Denmark
  7. 7IDIAP Jordi Gol, Barcelona, Spain
  8. 8Specialty Clinical Development, Neurology and Psychiatry, Teva Pharmaceuticals USA Inc, North Wales, Pennsylvania, USA
  9. 9Health Search, Italian College of General Practitioners and Primary Care, Florence, Italy
  10. 10Hospital del Mar Institute for Medical Research, Barcelona, Spain
  11. 11Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
  12. 12Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands
  13. 13Department of Neurology, Vrije Universiteit, Amsterdam, The Netherlands
  14. 14Department of Neurobiology, Karolinska Institutet, Stockholm, Sweden
  15. 15South London and Maudsley NHS Foundation Trust, London, UK
  1. Correspondence to Dr Robert Stewart; robert.stewart{at}kcl.ac.uk

Abstract

Objective The objective of the study is to compare body mass index (BMI), systolic/diastolic blood pressure (SBP/DBP) and serum total cholesterol levels between dementia cases and controls at multiple time intervals prior to dementia onset, and to test time interval as a modifying factor for these associations.

Design Case–control study.

Setting Six European electronic health records databases.

Participants 291 780 cases at the date of first-recorded dementia diagnosis, compared with 29 170 549 controls randomly selected from the same databases, age matched and sex matched at this index date.

Exposure The following measures were extracted whenever recorded within each dataset: BMI (kg/m2), SBP and DBP (mm Hg) and serum total cholesterol (mmol/L). Levels for each of these variables were defined within six 2-year time intervals over the 12 years prior to the index date.

Main outcomes Case–control differences in exposures of interest were modelled for each time period and adjusted for demographic and clinical factors (ischaemic/unspecified stroke, type 2 diabetes mellitus, acute myocardial infarction, hypertension diagnosis, antihypertensive medication, cholesterol-lowering medication). Coefficients and interactions with time period were meta-analysed across the six databases.

Results Mean BMI (coefficient −1.16 kg/m2; 95% CI –1.38 to 0.93) and SBP (−2.83 mm Hg; 95% CI –4.49 to –1.16) were lower in cases at diagnosis, and case–control differences were greater in more recent time periods, as indicated by significant case-x-time interaction and case-x-time-squared interaction terms. Time variations in coefficients for cholesterol levels were less consistent between databases and those for DBP were largely not significant.

Conclusion Routine clinical data show emerging divergence in levels of BMI and SBP prior to the diagnosis of dementia but less evidence for DBP or total cholesterol levels. These divergences should receive at least some consideration in routine dementia risk screening, although underlying mechanisms still require further investigation.

  • dementia
  • physiology
  • health informatics
  • hypertension
  • epidemiology
  • mental health
https://creativecommons.org/licenses/by/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

https://doi.org/10.1136/bmjopen-2020-038753

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    Footnotes

    • Twitter @TDuarte_Salles, @mmayerp

    • Contributors The analysis was conceived and designed by RS, PRR, PJV, MA, MFG, FL and JvDL. Data extractions and advice on analysis design were provided by the data controllers (DA, TD-S, MAM, AP, LP, JvDL) in liaison with PRR and PA. Analyses were carried out by LP and GP. The manuscript was written by GP and RS. Further comments and significant input were obtained from all coauthors who also oversaw the planning and development of the project.

    • Funding The research leading to these results has received support from the Innovative Medicines Initiative (IMI) Joint Undertaking under EMIF grant agreement n° 115372, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution. RS and GP are part-funded by the National Institute for Health Research (NIHR) Biomedical Research Centre and Dementia Biomedical Research Unit at South London and Maudsley NHS Foundation Trust and King's College London.

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement No additional data are available. The datasets analysed during the current study are not publicly available due to confidentially of patients but are available via application to individual data custodians under the EMIF platform (http://www.emif.eu/). The data provided by each database owners were already anonymised.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.