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Silent brain infarctions and cognition decline: systematic review and meta-analysis

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Abstract

Background

Silent brain infarction (SBI) may be associated with cognitive decline in the general population. We systematically reviewed prior literature on: (1) SBI and cognition cross-sectionally; (2) baseline SBI and future cognitive decline and risk for cognitive disorders including dementia, and (3) incident SBI and the emergence of cognitive decline or cognitive disorders.

Methods

The MEDLINE and EMBASE databases were searched for relevant studies. Data were independently extracted by two reviewers. Quality was assessed using the Newcastle Ottawa Scale. Data were pooled using a random effects model when more than two comparable estimates were found.

Results

Thirty relevant studies were identified: 17 had a cross-sectional design, 10 evaluated the association of baseline SBI with future cognitive decline, and 5 evaluated the association of incident SBI with cognitive decline. Most cross-sectional studies reported lower cognitive performance in persons with SBI. The pooled risk for incident dementia in persons with SBI was 1.48 (95% CI 1.12–1.97), but there was significant heterogeneity (p = 0.009); removing one outlier eliminated the heterogeneity (p = 0.53), giving a lower but still significant estimate (hazard ratio 1.27, 95% CI 1.06–1.51). The pooled risk for incident MCI was not increased in persons with SBI (hazard ratio 0.83, 95% CI 0.40 to 1.72), but there was significant heterogeneity (p < 0.001). The appearance of new SBI was associated with steeper rate of cognitive decline and the appearance of dementia.

Conclusions

SBI are associated with worse cognition and increased risk for dementia. More standardization of cognitive assessment methods would facilitate future cross-study comparisons.

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Acknowledgements

The work was funded by the Katthy Taylor Chair in Vascular Dementia (University of Calgary), held by Dr. Smith. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr. Smith has had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The study dataset will be made available to other researchers on request to Dr. Smith.

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Authors and Affiliations

  1. Neurology, Department of Clinical Neurosciences, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada

    Feeha Azeem, Romella Durrani, Charlotte Zerna & Eric E. Smith

  2. Hotchkiss Brain Institute, Calgary, AB, Canada

    Romella Durrani, Charlotte Zerna & Eric E. Smith

  3. Calgary Stroke Program, Calgary, AB, Canada

    Charlotte Zerna & Eric E. Smith

  4. Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada

    Charlotte Zerna & Eric E. Smith

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  1. Feeha Azeem
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  2. Romella Durrani
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  3. Charlotte Zerna
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  4. Eric E. Smith
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Correspondence to Eric E. Smith.

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Conflicts of interest

Dr. Smith reports funding from the Canadian Institutes of Health Research and Brain Canada for studies of biomarkers of cerebral small vessel disease, and consulting fees from Portola Pharmaceuticals and Alnylam Pharmaceuticals for activities outside the submitted work. The other authors report no relevant financial conflicts of interest.

Ethical standard statement

Approval by an Institutional Review Board was not needed because this was a systematic review based on published work, with no interactions with study participants.

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Azeem, F., Durrani, R., Zerna, C. et al. Silent brain infarctions and cognition decline: systematic review and meta-analysis. J Neurol 267, 502–512 (2020). https://doi.org/10.1007/s00415-019-09534-3

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