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Cognitive impact of cerebral microbleeds in patients with symptomatic small vessel disease

Research output: Contribution to journalArticlepeer-review

for the DNA Lacunar 2 investigators

Original languageEnglish
JournalInternational Journal Of Stroke
Accepted/In press2021
Published7 May 2021

Bibliographical note

Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was funded by a British Heart Foundation programme grant (RG/4/32218). Recruitment was supported by the NIHR Clinical Research Network. S.N.’s salary is funded by an MRC experimental medicine grant (MR/N026896/1). R.B.B. is the recipient of an ABN Clinical Research Training Fellowship funded by Guarantors of Brain. H.S.M. is supported by an NIHR Senior Investigator award. Infrastructural support was provided by the Cambridge University Hospitals NIHR Biomedical Research Center. The views expressed are those of the authors and not necessarily the views of the NHS, the NIHR, or the Department of Health and Social Care. Publisher Copyright: © 2021 World Stroke Organization. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors


Background and aim: Whether cerebral microbleeds cause cognitive impairment remains uncertain. We analyzed whether cerebral microbleeds are associated with cognitive dysfunction in patients with symptomatic cerebral small vessel disease, and whether this association is independent of other neuroimaging markers of cerebral small vessel disease. Methods: We analyzed consecutive patients with MRI-confirmed lacunar stroke included in DNA-Lacunar-2 multicenter study. Cerebral microbleeds were graded using the Brain Observer Microbleed Rating Scale (BOMBS). Neuropsychological assessment was performed using the Brief Memory and Executive Test (BMET). We analyzed the association between cerebral microbleeds, BMET, and the following subdomains: executive function/processing speed and orientation/memory. We also searched for an independent association between cerebral microbleeds and vascular cognitive impairment, defined as BMET ≤ 13. Results: Out of 688 included patients, cerebral microbleeds were detected in 192 (27.9%). After adjusting for white matter hyperintensities severity, lacune count, and other confounders, both the presence and the number of cerebral microbleeds were significantly associated with impaired cognitive performance [β = −13.0; 95% CI = (−25.3, −0.6) and β = −13.1; 95% CI = (−19.8, −6.4), respectively]. On analysis of specific cognitive domains, associations were present for executive function/processing speed [β = −5.8; 95% CI = (−9.3, −2.2) and β = −4.3; 95% CI = (−6.2, −2.4), respectively] but not for orientation/memory [β = −0.4; 95% CI = (−4.0, 3.2) and β = −2.1; 95% CI = (−4.0, 0.1), respectively]. We also found an independent association between the presence and the number of cerebral microbleeds and vascular cognitive impairment [adjusted OR = 1.48; 95% CI = (1.01, 2.18) and OR = 1.43; 95% CI = (1.15, 1.79), respectively]. Conclusion: In a large cohort of symptomatic cerebral small vessel disease patients, after controlling for other neuroimaging markers of cerebral small vessel disease severity, cerebral microbleeds were associated with cognitive dysfunction. Executive function and processing speed were predominantly impaired. This might suggest a causal role of cerebral microbleeds in determining vascular cognitive impairment.

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