Skip to main content

Advertisement

SpringerLink
Log in

Cerebral microbleeds and the risk of mortality in the general population

  • NEUROEPIDEMIOLOGY
  • Published:
European Journal of Epidemiology Aims and scope Submit manuscript

Abstract

Presence of cerebral microbleeds indicates underlying vascular brain disease and has been implicated in lobar hemorrhages and dementia. However, it remains unknown whether microbleeds also reflect more systemic vascular burden. We investigated the association of microbleeds with all-cause and cardiovascular related mortality in the general population. We rated the brain magnetic resonance imaging scans of 3979 Rotterdam Scan Study participants to determine presence, number, and location of microbleeds. Cox proportional hazards models, adjusted for age, sex, subcohort, vascular risk factors, and other MRI markers of cerebral vascular disease, were applied to quantify the association of microbleeds with mortality. After a mean follow up of 5.2 (±1.1) years, 172 (4.3 %) people had died. Presence of microbleeds, and particularly deep or infratentorial microbleeds, was significantly associated with an increased risk of all-cause mortality [sex-, age-, subcohort adjusted hazard ratio (HR) 2.27; CI 1.50–3.45], independent of vascular risk factors (HR 1.87; 95 % CI 1.20–2.92). The presence of deep or infratentorial microbleeds strongly associated with the risk of cardiovascular related mortality (HR 4.08; CI 1.78–9.39). Mortality risk increased with increasing number of microbleeds. The presence of microbleeds, particularly multiple microbleeds and those in deep or infratentorial regions, indicates an increased risk of mortality, independent of other MRI markers of cerebral vascular disease. Our data suggest that microbleeds may mark severe underlying vascular pathology associated with poorer survival.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

APOE-e4:

Apolipoprotein E4

CMBs:

Cerebral microbleeds

HDL:

High-density lipoprotein

HR:

Hazard ratio

MRI:

Magnetic resonance imaging

WML:

White matter lesions

References

  1. World Health Organization. Cardiovascular diseases. Fact sheet number 317. 2013. Available at: http://www.who.int/mediacentre/factsheets/fs317/en/index.html. Accessed 1 July 2013.

  2. Gaziano TA. Cardiovascular disease in the developing world and its cost-effective management. Circulation. 2005;112:3547–53.

    Article  PubMed  Google Scholar 

  3. Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 2010;9:689–701.

    Article  PubMed  Google Scholar 

  4. Barclay LL, Zemcov A, Blass JP, Sansone J. Survival in Alzheimer’s disease and vascular dementias. Neurology. 1985;35:834–40.

    Article  PubMed  CAS  Google Scholar 

  5. Borjesson-Hanson A, Gustafson D, Skoog I. Five-year mortality in relation to dementia and cognitive function in 95-year-olds. Neurology. 2007;69:2069–75.

    Article  PubMed  Google Scholar 

  6. Feng W, Hendry RM, Adams RJ. Risk of recurrent stroke, myocardial infarction, or death in hospitalized stroke patients. Neurology. 2010;74:588–93.

    Article  Google Scholar 

  7. Melkas S, Putaala J, Oksala NK, Pohjasvaara T, Oksala A, Kaste M, et al. Small-vessel disease relates to poor poststroke survival in a 12-year follow-up. Neurology. 2011;76:734–9.

    Article  PubMed  CAS  Google Scholar 

  8. Wang TJ. Assessing the role of circulating, genetic, and imaging biomarkers in cardiovascular risk prediction. Circulation. 2011;123:551–65.

    Article  PubMed  Google Scholar 

  9. Patel B, Markus HS. Magnetic resonance imaging in cerebral small vessel disease and its use as a surrogate disease marker. Int J Stroke. 2011;6:47–59.

    Article  PubMed  Google Scholar 

  10. Henneman WJ, Sluimer JD, Cordonnier C, Baak MM, Scheltens P, Barkhof F, et al. MRI biomarkers of vascular damage and atrophy predicting mortality in a memory clinic population. Stroke. 2009;40:492–8.

    Article  PubMed  Google Scholar 

  11. Ikram MA, Vrooman HA, Vernooij MW, van der Lijn F, Hofman A, van der Lugt A, et al. Brain tissue volumes in the general elderly population. The Rotterdam Scan Study. Neurobiol Aging. 2008;29:882–90.

    Article  PubMed  Google Scholar 

  12. Levy RM, Steffens DC, McQuoid DR, Provenzale JM, MacFall JR, Krishnan KR. MRI lesion severity and mortality in geriatric depression. Am J Geriatr Psychiatry. 2003;11:678–82.

    PubMed  Google Scholar 

  13. Poels MM, Vernooij MW, Ikram MA, Hofman A, Krestin GP, van der Lugt A, et al. Prevalence and risk factors of cerebral microbleeds: an update of the Rotterdam Scan Study. Stroke. 2010;41:S103–6.

    Article  PubMed  Google Scholar 

  14. Vernooij MW, van der Lugt A, Ikram MA, Wielopolski PA, Niessen WJ, Hofman A, et al. Prevalence and risk factors of cerebral microbleeds: the Rotterdam Scan Study. Neurology. 2008;70:1208–14.

    Article  PubMed  CAS  Google Scholar 

  15. Fazekas F, Kleinert R, Roob G, Kleinert G, Kapeller P, Schmidt R, et al. Histopathologic analysis of foci of signal loss on gradient-echo T2*-weighted MR images in patients with spontaneous intracerebral hemorrhage: evidence of microangiopathy-related microbleeds. AJNR Am J Neuroradiol. 1999;20:637–42.

    PubMed  CAS  Google Scholar 

  16. Altmann-Schneider I, Trompet S, de Craen AJ, van Es AC, Jukema JW, Stott DJ, et al. Cerebral microbleeds are predictive of mortality in the elderly. Stroke. 2011;42:638–44.

    Article  PubMed  Google Scholar 

  17. Hofman A, van Duijn CM, Franco OH, Ikram MA, Janssen HL, Klaver CC, et al. The Rotterdam study: 2012 objectives and design update. Eur J Epidemiol. 2011;26:657–86.

    Article  PubMed  Google Scholar 

  18. Ikram MA, van der Lugt A, Niessen WJ, Krestin GP, Koudstaal PJ, Hofman A, et al. The Rotterdam Scan Study: design and update up to 2012. Eur J Epidemiol. 2011;26:811–24.

    Article  PubMed  Google Scholar 

  19. Vernooij MW, Ikram MA, Wielopolski PA, Krestin GP, Breteler MM, van der Lugt A. Cerebral microbleeds: accelerated 3D T2*-weighted GRE MR imaging versus conventional 2D T2*-weighted GRE MR imaging for detection. Radiology. 2008;248:272–277.

    Article  PubMed  Google Scholar 

  20. Ikram MA, Vernooij MW, Hofman A, Niessen WJ, van der Lugt A, Breteler MM. Kidney function is related to cerebral small vessel disease. Stroke. 2008;39:55–61.

    Article  PubMed  Google Scholar 

  21. Leening MJ, Kavousi M, Heeringa J, van Rooij FJ, Verkroost-van Heemst J, Deckers JW, et al. Methods of data collection and definitions of cardiac outcomes in the Rotterdam study. Eur J Epidemiol. 2012;27:173–85.

    Article  PubMed  Google Scholar 

  22. Wenham PR, Price WH, Blandell G. Apolipoprotein E genotyping by one-stage PCR. Lancet. 1991;337:1158–9.

    Article  PubMed  CAS  Google Scholar 

  23. Biffi A, Halpin A, Towfighi A, Gilson A, Busl K, Rost N, et al. Aspirin and recurrent intracerebral hemorrhage in cerebral amyloid angiopathy. Neurology. 2010;75:693–8.

    Article  PubMed  CAS  Google Scholar 

  24. Soo YO, Yang SR, Lam WW, Wong A, Fan YH, Leung HH, et al. Risk vs benefit of anti-thrombotic therapy in ischaemic stroke patients with cerebral microbleeds. J Neurol. 2008;255:1679–86.

    Article  PubMed  Google Scholar 

  25. Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, et al. Heart disease and stroke statistics—2012 update: a report from the American Heart Association. Circulation. 2012;125:e2–220.

    Article  PubMed  Google Scholar 

  26. Doubal FN, MacGillivray TJ, Patton N, Dhillon B, Dennis MS, Wardlaw JM. Fractal analysis of retinal vessels suggests that a distinct vasculopathy causes lacunar stroke. Neurology. 2010;74:1102–7.

    Article  PubMed  CAS  Google Scholar 

  27. Lanfranconi S, Markus HS. COL4A1 mutations as a monogenic cause of cerebral small vessel disease: a systematic review. Stroke. 2010;41:e513–8.

    Article  PubMed  Google Scholar 

  28. Thompson CS, Hakim AM. Living beyond our physiological means: small vessel disease of the brain is an expression of a systemic failure in arteriolar function: a unifying hypothesis. Stroke. 2009;40:e322–30.

    Article  PubMed  Google Scholar 

  29. Viswanathan A, Greenberg SM. Cerebral amyloid angiopathy in the elderly. Ann Neurol. 2011;70:871–80.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam; the Research Institute for Diseases in the Elderly; the Ministry of Education, Culture, and Science; the Ministry for Health, Welfare, and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. Dr. Ikram was supported by the Netherlands Heart Foundation (2012T008). The current study is supported by a research fellowship (MWV) from Erasmus MC University Medical Center, Rotterdam, The Netherlands. The funding sources had no influence on study design, collection, analysis, or interpretation of the data or approval of the manuscript.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Office secretariat Epidemiology: Na 28-18, PO Box 2040, 3000 CA, Rotterdam, The Netherlands

    Saloua Akoudad, Mohammad Arfan Ikram, Albert Hofman & Meike Willemijn Vernooij

  2. Department of Radiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

    Saloua Akoudad, Mohammad Arfan Ikram, Aad van der Lugt & Meike Willemijn Vernooij

  3. Department of Neurology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

    Saloua Akoudad, Mohammad Arfan Ikram & Peter Jan Koudstaal

Authors
  1. Saloua Akoudad
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohammad Arfan Ikram
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter Jan Koudstaal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Albert Hofman
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Aad van der Lugt
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Meike Willemijn Vernooij
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Meike Willemijn Vernooij.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Akoudad, S., Ikram, M.A., Koudstaal, P.J. et al. Cerebral microbleeds and the risk of mortality in the general population. Eur J Epidemiol 28, 815–821 (2013). https://doi.org/10.1007/s10654-013-9854-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10654-013-9854-3

Keywords

Search

Navigation