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March 08, 2019Article

Clinical relevance of acute cerebral microinfarcts in vascular cognitive impairment

Doeschka A. Ferro, Hilde van den Brink, Lieza G. Exalto, Jooske M.F. Boomsma, Frederik Barkhof, Niels D. Prins, Wiesje M. van der Flier, Geert Jan Biessels, on behalf of the TRACE-VCI study group
First published March 8, 2019, DOI: https://doi.org/10.1212/WNL.0000000000007250
Doeschka A. Ferro
From the Department of Neurology (D.A.F., H.v.d.B., L.G.E., J.M.F.B., G.J.B.), Brain Center UMC Utrecht, University Medical Center Utrecht, Utrecht University; Department of Neurology (J.M.F.B.), Onze Lieve Vrouwe Gasthuis (OLVG) West; Department of Radiology & Nuclear Medicine (F.B.) Department of Neurology and Alzheimer Center Amsterdam (N.D.P., W.M.v.d.F.), Department of Epidemiology & Biostatistics (W.M.v.d.F.), Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK.
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Hilde van den Brink
From the Department of Neurology (D.A.F., H.v.d.B., L.G.E., J.M.F.B., G.J.B.), Brain Center UMC Utrecht, University Medical Center Utrecht, Utrecht University; Department of Neurology (J.M.F.B.), Onze Lieve Vrouwe Gasthuis (OLVG) West; Department of Radiology & Nuclear Medicine (F.B.) Department of Neurology and Alzheimer Center Amsterdam (N.D.P., W.M.v.d.F.), Department of Epidemiology & Biostatistics (W.M.v.d.F.), Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK.
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Lieza G. Exalto
From the Department of Neurology (D.A.F., H.v.d.B., L.G.E., J.M.F.B., G.J.B.), Brain Center UMC Utrecht, University Medical Center Utrecht, Utrecht University; Department of Neurology (J.M.F.B.), Onze Lieve Vrouwe Gasthuis (OLVG) West; Department of Radiology & Nuclear Medicine (F.B.) Department of Neurology and Alzheimer Center Amsterdam (N.D.P., W.M.v.d.F.), Department of Epidemiology & Biostatistics (W.M.v.d.F.), Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK.
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Jooske M.F. Boomsma
From the Department of Neurology (D.A.F., H.v.d.B., L.G.E., J.M.F.B., G.J.B.), Brain Center UMC Utrecht, University Medical Center Utrecht, Utrecht University; Department of Neurology (J.M.F.B.), Onze Lieve Vrouwe Gasthuis (OLVG) West; Department of Radiology & Nuclear Medicine (F.B.) Department of Neurology and Alzheimer Center Amsterdam (N.D.P., W.M.v.d.F.), Department of Epidemiology & Biostatistics (W.M.v.d.F.), Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK.
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Frederik Barkhof
From the Department of Neurology (D.A.F., H.v.d.B., L.G.E., J.M.F.B., G.J.B.), Brain Center UMC Utrecht, University Medical Center Utrecht, Utrecht University; Department of Neurology (J.M.F.B.), Onze Lieve Vrouwe Gasthuis (OLVG) West; Department of Radiology & Nuclear Medicine (F.B.) Department of Neurology and Alzheimer Center Amsterdam (N.D.P., W.M.v.d.F.), Department of Epidemiology & Biostatistics (W.M.v.d.F.), Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK.
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Niels D. Prins
From the Department of Neurology (D.A.F., H.v.d.B., L.G.E., J.M.F.B., G.J.B.), Brain Center UMC Utrecht, University Medical Center Utrecht, Utrecht University; Department of Neurology (J.M.F.B.), Onze Lieve Vrouwe Gasthuis (OLVG) West; Department of Radiology & Nuclear Medicine (F.B.) Department of Neurology and Alzheimer Center Amsterdam (N.D.P., W.M.v.d.F.), Department of Epidemiology & Biostatistics (W.M.v.d.F.), Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK.
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Wiesje M. van der Flier
From the Department of Neurology (D.A.F., H.v.d.B., L.G.E., J.M.F.B., G.J.B.), Brain Center UMC Utrecht, University Medical Center Utrecht, Utrecht University; Department of Neurology (J.M.F.B.), Onze Lieve Vrouwe Gasthuis (OLVG) West; Department of Radiology & Nuclear Medicine (F.B.) Department of Neurology and Alzheimer Center Amsterdam (N.D.P., W.M.v.d.F.), Department of Epidemiology & Biostatistics (W.M.v.d.F.), Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK.
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Geert Jan Biessels
From the Department of Neurology (D.A.F., H.v.d.B., L.G.E., J.M.F.B., G.J.B.), Brain Center UMC Utrecht, University Medical Center Utrecht, Utrecht University; Department of Neurology (J.M.F.B.), Onze Lieve Vrouwe Gasthuis (OLVG) West; Department of Radiology & Nuclear Medicine (F.B.) Department of Neurology and Alzheimer Center Amsterdam (N.D.P., W.M.v.d.F.), Department of Epidemiology & Biostatistics (W.M.v.d.F.), Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK.
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From the Department of Neurology (D.A.F., H.v.d.B., L.G.E., J.M.F.B., G.J.B.), Brain Center UMC Utrecht, University Medical Center Utrecht, Utrecht University; Department of Neurology (J.M.F.B.), Onze Lieve Vrouwe Gasthuis (OLVG) West; Department of Radiology & Nuclear Medicine (F.B.) Department of Neurology and Alzheimer Center Amsterdam (N.D.P., W.M.v.d.F.), Department of Epidemiology & Biostatistics (W.M.v.d.F.), Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK.
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Clinical relevance of acute cerebral microinfarcts in vascular cognitive impairment
Doeschka A. Ferro, Hilde van den Brink, Lieza G. Exalto, Jooske M.F. Boomsma, Frederik Barkhof, Niels D. Prins, Wiesje M. van der Flier, Geert Jan Biessels, on behalf of the TRACE-VCI study group
Neurology Mar 2019, 10.1212/WNL.0000000000007250; DOI: 10.1212/WNL.0000000000007250

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Abstract

Objective To determine the occurrence of acute cerebral microinfarcts (ACMIs) in memory clinic patients and relate their presence to vascular risk and cognitive profile, CSF and neuroimaging markers, and clinical outcome.

Methods The TRACE-VCI study is a memory clinic cohort of patients with vascular brain injury on MRI (i.e., possible vascular cognitive impairment [VCI]). We included 783 patients (mean age 67.6 ± 8.5, 46% female) with available 3T diffusion-weighted imaging (DWI). ACMIs were defined as supratentorial DWI hyperintensities <5 mm with a corresponding hypo/isointense apparent diffusion coefficient signal and iso/hyperintense T2*-weighted signal.

Results A total of 23 ACMIs were found in 16 of the 783 patients (2.0%). Patients with ACMIs did not differ in vascular risk or cognitive profile, but were more often diagnosed with vascular dementia (odds ratio [OR] 5.1; 95% confidence interval [CI] 1.4–18.9, p = 0.014). ACMI presence was associated with lower levels of β-amyloid (p < 0.004) and with vascular imaging markers (lacunar infarcts: OR 3.5, CI 1.3–9.6, p = 0.015; nonlacunar infarcts: OR 4.1, CI 1.4–12.5, p = 0.012; severe white matter hyperintensities: OR 4.8, CI 1.7–13.8, p = 0.004; microbleeds: OR 18.9, CI 2.5–144.0, p = 0.0001). After a median follow-up of 2.1 years, the risk of poor clinical outcome (composite of marked cognitive decline, major vascular event, death, and institutionalization) was increased among patients with ACMIs (hazard ratio 3.0; 1.4–6.0, p = 0.005).

Conclusion In patients with possible VCI, ACMI presence was associated with a high burden of cerebrovascular disease of both small and large vessel etiology and poor clinical outcome. ACMIs may thus be a novel marker of active vascular brain injury in these patients.

Footnotes

  • ↵* These authors contributed equally to this work.

  • Received June 12, 2018.
  • Accepted in final form November 24, 2018.
  • © 2019 American Academy of Neurology

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Disputes & Debates: Rapid online correspondence

  • Author response: Clinical relevance of acute cerebral microinfarcts in vascular cognitive impairment
    • Doeschka A. Ferro, PhD Candidate, Department of Neurology, UMC Utrecht Brain Center, Utrecht University
    • , Neurologist, Department of Neurology, UMC Utrecht Brain Center, Utrecht University
    Published May 07, 2019
  • Reader response: Clinical relevance of acute cerebral microinfarcts in vascular cognitive impairment
    • Shugang Cao, Neurologist, Department of Neurology, Hefei Affiliated Hospital of Anhui Medical University
    • , Neurologist, Department of Neurology, Hefei Affiliated Hospital of Anhui Medical University
    Published March 29, 2019

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  • MRI
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