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Association of visit-to-visit variability in blood pressure with cognitive function in old age: prospective cohort study

BMJ 2013; 347 doi: (Published 30 July 2013) Cite this as: BMJ 2013;347:f4600
  1. Behnam Sabayan, PhD student12,
  2. Liselotte W Wijsman, PhD student13,
  3. Jessica C Foster-Dingley, PhD student4,
  4. David J Stott, professor5,
  5. Ian Ford, professor6,
  6. Brendan M Buckley, professor7,
  7. Naveed Sattar, professor8,
  8. J Wouter Jukema, professor9,
  9. Matthias J P van Osch, magnetic resonance imaging physicist2,
  10. Jeroen van der Grond, senior neuroradiology researcher2,
  11. Mark A van Buchem, professor2,
  12. Rudi G J Westendorp, professor13,
  13. Anton J M de Craen, senior epidemiologist13,
  14. Simon P Mooijaart, internist and clinical researcher1310
  1. 1Department of Gerontology and Geriatrics, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, Netherlands
  2. 2Department of Radiology, Leiden University Medical Center, Netherlands
  3. 3Netherlands Consortium for Healthy Ageing, Leiden, Netherlands
  4. 4Department of Psychiatry, Leiden University Medical Center, Netherlands
  5. 5Academic Section of Geriatrics, Faculty of Medicine, University of Glasgow, UK
  6. 6Robertson Center for Biostatistics, University of Glasgow, UK
  7. 7Department of Pharmacology and Therapeutics, University College Cork, Ireland
  8. 8British Heart Foundation, Glasgow Cardiovascular Research Centre, University of Glasgow, UK
  9. 9Department of Cardiology, Leiden University Medical Center, Leiden, Netherlands
  10. 10Institute for Evidence-Based Medicine in Old age, Leiden, the Netherlands
  1. Correspondence to: S P Mooijaart s.p.mooijaart{at}
  • Accepted 12 July 2013


Objective To investigate the association between visit-to-visit variability in blood pressure and cognitive function in old age (>70 years).

Design Prospective cohort study.

Setting PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) study, a collaboration between centres in Ireland, Scotland, and the Netherlands.

Participants 5461 participants, mean age 75.3 years, who were at risk of cardiovascular disease. Blood pressure was measured every three months during an average of 3.2 years. Visit-to-visit variability in blood pressure was defined as the standard deviation of blood pressure measurements between visits.

Main outcome measures Four domains of cognitive function, testing selective attention, processing speed, and immediate and delayed memory. In a magnetic resonance imaging substudy of 553 participants, structural brain volumes, cerebral microbleeds, infarcts, and white matter hyperintensities were measured.

Results Participants with higher visit-to-visit variability in systolic blood pressure had worse performance on all cognitive tests: attention (mean difference high versus low thirds) 3.08 seconds (95% confidence interval 0.85 to 5.31), processing speed −1.16 digits coded (95% confidence interval −1.69 to −0.63), immediate memory −0.27 pictures remembered (95% confidence interval −0.41 to −0.13), and delayed memory −0.30 pictures remembered (95% confidence interval −0.49 to −0.11). Furthermore, higher variability in both systolic and diastolic blood pressure was associated with lower hippocampal volume and cortical infarcts, and higher variability in diastolic blood pressure was associated with cerebral microbleeds (all P<0.05). All associations were adjusted for average blood pressure and cardiovascular risk factors.

Conclusion Higher visit-to-visit variability in blood pressure independent of average blood pressure was associated with impaired cognitive function in old age.


  • We thank Stella Trompet for her kind collaboration in data analysis.

  • Contributors: BS and LWW contributed equally to the work. They formulated the research question, analysed and interpreted the data, and drafted the manuscript. JCF-D analysed and interpreted the data. DJS, IF, BMB, NS, and JWJ designed the study and revised the manuscript. MJPvO, JvdG interpreted the data and revised the manuscript. MAvB designed the study and interpreted the data. RGJW designed the study, interpreted the data, and revised the draft. AJMdC and SPM formulated the research question, interpreted the data, and revised the manuscript. SPM is guarantor.

  • Funding: The original PROSPER clinical trial was funded by an investigator initiated grant from Bristol-Myers Squibb, USA. However, the company had no involvement in the formulation of hypotheses, analysis of the data, or in any aspect of the preparation of this manuscript.

  • 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 the institutional ethics committees of the three collaborating centers. All participants gave written informed consent.

  • Data sharing: No additional data available.

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