Skip to main content

Advertisement

SpringerLink
Log in

Strictly Lobar Cerebral Microbleeds Are Associated with Increased White Matter Volume

  • Original Article
  • Published:
Translational Stroke Research Aims and scope Submit manuscript

Abstract

Cerebral small vessel diseases (CSVD), such as white matter hyperintensities (WMH), have been acknowledged as a cause of brain atrophy. However, the relationship between brain volumes and cerebral microbleeds (CMBs) has not yet been determined. We aimed to evaluate whether the presence and topography of CMBs are associated with altered volumes of gray matter (GMV) and white matter (WMV). Non-stroke and non-demented subjects were prospectively recruited from the I-Lan Longitudinal Aging Study. High-resolution 3-T MRI was performed to quantify total and regional WMV and GMV, including Alzheimer’s disease-susceptible areas. CMBs were assessed with susceptibility-weighted imaging. Six hundred and fifty-nine subjects (62.1 ± 8.3 years, 290 (44%) men) were included. Thirty-two (4.9%) subjects had strictly lobar CMBs (SL-CMBs) and 51 (7.7%) had deep or infratentorial CMBs (DI-CMBs). We observed an association between CMBs and WMV, independent of age, sex, and vascular risk factors; the direction of association depended on the location of the CMBs. The SL-CMB group had an increased total, frontal, and occipital WMV compared with the no-CMB group, which remained significant after adjusting for other CSVDs (WMH volumes and lacune numbers). In contrast, the DI-CMB group had a decreased occipital WMV compared to the no-CMB group. However, this significance disappeared after taking other CSVDs into consideration. Our results showed no relationship between CMBs and GMV. In conclusion, the increased WMV in non-stroke, non-demented subjects with SL-CMBs observed here provides insight into the early pathogenesis of SL-CMBs. This may be a result of increased water content or amyloid accumulation.

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
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Wering DJ. Cerebral microbleeds: pathophysiology to clinical practice. 1st ed. Cambridge: Cambridge University Press; 2011.

    Book  Google Scholar 

  2. Yates PA, Villemagne VL, Ellis KA, Desmond PM, Masters CL, Rowe CC. Cerebral microbleeds: a review of clinical, genetic, and neuroimaging associations. Front Neurol. 2014;4:205.

    Article  Google Scholar 

  3. Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R, et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013;12:822–38.

    Article  Google Scholar 

  4. Jokinen H, Lipsanen J, Schmidt R, Fazekas F, Gouw AA, van der Flier WM, et al. Brain atrophy accelerates cognitive decline in cerebral small vessel disease: the LADIS study. Neurology. 2012;78:1785–92.

    Article  CAS  Google Scholar 

  5. Nitkunan A, Lanfranconi S, Charlton RA, Barrick TR, Markus HS. Brain atrophy and cerebral small vessel disease: a prospective follow-up study. Stroke. 2011;42:133–8.

    Article  Google Scholar 

  6. Raji CA, Lopez OL, Kuller LH, Carmichael OT, Longstreth WT Jr, Gach HM, et al. White matter lesions and brain gray matter volume in cognitively normal elders. Neurobiol Aging. 2012;33:834.e7–16.

    Article  Google Scholar 

  7. Chung CP, Chou KH, Chen WT, Liu LK, Lee WJ, Chen LK, et al. Strictly lobar cerebral microbleeds are associated with cognitive impairment. Stroke. 2016;47:2497–502.

    Article  Google Scholar 

  8. Chung CP, Chou KH, Chen WT, Liu LK, Lee WJ, Chen LK, et al. Cerebral microbleeds are associated with physical frailty: a community-based study. Neurobiol Aging. 2016;44:143–50.

    Article  Google Scholar 

  9. Lee WJ, Liu LK, Peng LN, Lin MH, Chen LK, ILAS Research Group. Comparisons of sarcopenia defined by IWGS and EWGSOP criteria among older people: results from the I-Lan longitudinal aging study. J Am Med Dir Assoc. 2013;14:528.e1–7.

    Google Scholar 

  10. Liu HC, Lin KN, Teng EL, Wang SJ, Fuh JL, Guo NW, et al. Prevalence and subtypes of dementia in Taiwan: a community survey of 5297 individuals. J Am Geriatr Soc. 1995;43:144–9.

    Article  CAS  Google Scholar 

  11. Jones DW, Hall JE. Seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure and evidence from new hypertension trials. Hypertension. 2004;43:1–3.

    Article  CAS  Google Scholar 

  12. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010;33(Suppl 1):S62–9.

    Article  Google Scholar 

  13. Levey AS, Eckardt KU, Tsukamoto Y, Levin A, Coresh J, Rossert J, et al. Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2005;67:2089–100.

    Article  Google Scholar 

  14. Ashburner J. A fast diffeomorphic image registration algorithm. Neuroimage. 2007;38:95–113.

    Article  Google Scholar 

  15. Ashburner J, Friston KJ. Voxel-based morphometry--the methods. Neuroimage. 2000;11:805–21.

    Article  CAS  Google Scholar 

  16. Schmidt P, Gaser C, Arsic M, Buck D, Förschler A, Berthele A, et al. An automated tool for detection of FLAIR-hyperintense white-matter lesions in multiple sclerosis. Neuroimage. 2012;59:3774–83.

    Article  Google Scholar 

  17. Kim KW, MacFall JR, Payne ME. Classification of white matter lesions on magnetic resonance imaging in elderly persons. Biol Psychiatry. 2008;64:273–80.

    Article  Google Scholar 

  18. Greenberg SM, Vernooij MW, Cordonnier C, Viswanathan A, Al-Shahi Salman R, Warach S, et al. Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol. 2009;8:165–74.

    Article  Google Scholar 

  19. Gregoire SM, Chaudhary UJ, Brown MM, Yousry TA, Kallis C, Jäger HR, et al. The Microbleed Anatomical Rating Scale (MARS): reliability of a tool to map brain microbleeds. Neurology. 2009;73:1759–66.

    Article  CAS  Google Scholar 

  20. Stark DD, Bradley WG. Magnetic Resonance Imaging. 3rd ed. St. Louis: Mosby; 1999.

    Google Scholar 

  21. Jeerakathil T, Wolf PA, Beiser A, Hald JK, Au R, Kase CS, et al. Cerebral microbleeds: prevalence and associations with cardiovascular risk factors in the Framingham Study. Stroke. 2004;35:1831–5.

    Article  Google Scholar 

  22. Graff-Radford J, Simino J, Kantarci K, Mosley TH Jr, Griswold ME, Windham BG, et al. Neuroimaging correlates of cerebral microbleeds: the ARIC study (atherosclerosis risk in communities). Stroke. 2017;48:2964–72.

    Article  Google Scholar 

  23. Jellison BJ, Field AS, Medow J, Lazar M, Salamat MS, Alexander AL. Diffusion tensor imaging of cerebral white matter: a pictorial review of physics, fiber tract anatomy, and tumor imaging patterns. AJNR Am J Neuroradiol. 2004;25:356–69.

    PubMed  Google Scholar 

  24. Wardlaw JM, Smith C, Dichgans M. Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging. Lancet Neurol. 2013;12:483–97.

    Article  Google Scholar 

  25. Farrall AJ, Wardlaw JM. Blood-brain barrier: ageing and microvascular disease--systematic review and meta-analysis. Neurobiol Aging. 2009;30:337–52.

    Article  CAS  Google Scholar 

  26. Martinez-Ramirez S, Pontes-Neto OM, Dumas AP, Auriel E, Halpin A, Quimby M, et al. Topography of dilated perivascular spaces in subjects from a memory clinic cohort. Neurology. 2013;80:1551–6.

    Article  Google Scholar 

  27. 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  Google Scholar 

  28. Yates PA, Sirisriro R, Villemagne VL, Farquharson S, Masters CL, Rowe CC, et al. Cerebral microhemorrhage and brain β-amyloid in aging and Alzheimer disease. Neurology. 2011;77:48–54.

    Article  CAS  Google Scholar 

  29. Tsai HH, Tsai LK, Chen YF, Tang SC, Lee BC, Yen RF, et al. Correlation of cerebral microbleed distribution to amyloid burden in patients with primary intracerebral hemorrhage. Sci Rep. 2017;7:44715.

    Article  CAS  Google Scholar 

  30. Yates PA, Desmond PM, Phal PM, Steward C, Szoeke C, Salvado O, et al. Incidence of cerebral microbleeds in preclinical Alzheimer disease. Neurology. 2014;82:1266–73.

    Article  CAS  Google Scholar 

  31. Taki Y, Thyreau B, Kinomura S, Sato K, Goto R, Kawashima R, et al. Correlations among brain gray matter volumes, age, gender, and hemisphere in healthy individuals. PLoS One. 2011;6:e22734.

    Article  CAS  Google Scholar 

  32. Beauchet O, Celle S, Roche F, Bartha R, Montero-Odasso M, Allali G, et al. Blood pressure levels and brain volume reduction: a systematic review and meta-analysis. J Hypertens. 2013;31:1502–16.

    Article  CAS  Google Scholar 

Download references

Funding

This study was funded by the Ministry of Science and Technology, Taiwan; the Taipei Veterans General Hospital, Taiwan; and the Veterans Affair Council of Taiwan (Chung: VGH V105C-055; MOST 104-2314-B-075-MY3; LK Chen: MOST 103-2633-B-400-002; MOST 105-3011-B-010-001; Veterans Affair Council of Taiwan 105-X2-2-1; Wang: NSC 101-2314-B-010; NSC 102-2314-B-010-051-MY2; Taipei VGH V104C-059).

Author information

Authors and Affiliations

  1. Department of Neurology, National Yang Ming University, Taipei, Taiwan

    Pei-Ning Wang & Chih-Ping Chung

  2. Aging and Health Research Center, National Yang Ming University, Taipei, Taiwan

    Pei-Ning Wang, Li-Ning Peng, Li-Kuo Liu, Wei-Ju Lee & Liang-Kung Chen

  3. Brain Research Center, National Yang Ming University, Taipei, Taiwan

    Pei-Ning Wang, Kun-Hsien Chou & Ching-Po Lin

  4. Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan

    Pei-Ning Wang & Chih-Ping Chung

  5. School of Medicine, Institute of Neuroscience, National Yang Ming University, Taipei, Taiwan

    Kun-Hsien Chou & Ching-Po Lin

  6. Department of Gerontology, National Yang Ming University, Taipei, Taiwan

    Li-Ning Peng, Li-Kuo Liu, Wei-Ju Lee & Liang-Kung Chen

  7. Center for Geriatric and Gerontology, Taipei Veterans General Hospital, Taipei, Taiwan

    Li-Ning Peng, Li-Kuo Liu & Liang-Kung Chen

  8. Institute of Public Health, National Yang Ming University, Taipei, Taiwan

    Wei-Ju Lee

  9. Department of Family Medicine, Taipei Veterans General Hospital Yuanshan Branch, Yilan, Taiwan

    Wei-Ju Lee

  10. Department of Neurology, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei, 112, Taiwan

    Chih-Ping Chung

Authors
  1. Pei-Ning Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kun-Hsien Chou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Li-Ning Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Li-Kuo Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wei-Ju Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Liang-Kung Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ching-Po Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Chih-Ping Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chih-Ping Chung.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee (The Institutional Review Board of National Yang Ming University approved the present study) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, PN., Chou, KH., Peng, LN. et al. Strictly Lobar Cerebral Microbleeds Are Associated with Increased White Matter Volume. Transl. Stroke Res. 11, 29–38 (2020). https://doi.org/10.1007/s12975-019-00704-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12975-019-00704-z

Keywords

Search

Navigation