Clinical relevance of acute cerebral microinfarcts in vascular cognitive impairment

Doeschka A. Ferro; Hilde van den Brink; TRACE-VCI Study Grp; Lieza G. Exalto; Jooske M. F. Boomsma; Frederik Barkhof; Niels D. Prins; Wiesje M. van der Flier; Geert Jan Biessels; M. R. Benedictus; J. Bremer; J. Leijenaar; B. M. Tijms; M. P. Wattjes; S. M. Heringa; L. J. Kappelle; Y. D. Reijmer; M. Hamaker; R. Faaij; M. Pleizier; E. Vriens; H. M. Boss; H. C. Weinstein; P. Scheltens; C. E. Teunissen; E. van den Berg; O. Groeneveld; R. Heinen; J. Verwer; J. de Bresser; H. J. Kuijf; H. L. Koek

doi:10.1212/WNL.0000000000007250

Clinical relevance of acute cerebral microinfarcts in vascular cognitive impairment

Doeschka A. Ferro^*
, Hilde van den Brink
, TRACE-VCI Study Grp
, Lieza G. Exalto
, Jooske M. F. Boomsma
, Frederik Barkhof
, Niels D. Prins
, Wiesje M. van der Flier
, Geert Jan Biessels
, M. R. Benedictus
, J. Bremer
, J. Leijenaar
, B. M. Tijms
, M. P. Wattjes
, S. M. Heringa
, L. J. Kappelle
, Y. D. Reijmer
, M. Hamaker
, R. Faaij
, M. Pleizier

E. Vriens, H. M. Boss, H. C. Weinstein, P. Scheltens, C. E. Teunissen, E. van den Berg, O. Groeneveld, R. Heinen, J. Verwer, J. de Bresser, H. J. Kuijf, H. L. Koek

^*Corresponding author for this work

University Medical Centre Utrecht
Onze Lieve Vrouwe Gasthuis West
King's College London
Vrije Universiteit Amsterdam
Radboud University Medical Center
Diakonessenhuis
VU University Medical Center

Research output: Contribution to journal › Article › Academic › peer-review

29 Citations (Scopus)

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

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 beta-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.

Original language	English
Pages (from-to)	E1558-E1566
Number of pages	9
Journal	Neurology
Volume	92
Issue number	14
DOIs	https://doi.org/10.1212/WNL.0000000000007250
Publication status	Published - 2 Apr 2019

Bibliographical note

Study funding
The TRACE-VCI study is supported by Vidi grant 917.11.384
and Vici Grant 918.16.616 from ZonMw, the Netherlands,
Organisation for Health Research and Development, and
grant 2010T073 from the Dutch Heart Association to
Geert Jan Biessels. Research of the Alzheimer Center
Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. The Alzheimer Center Amsterdam is supported by Stichting Alzheimer
Nederland and Stichting VUmc fonds. The clinical database structure was developed with funding from Stichting Dioraphte. F. Barkhof is supported by the NIHR UCLH Biomedical Research Center. The authors also acknowledge support from the Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation (CVON
2012-06 Heart Brain Connection), Dutch Federation of University Medical Centres, the Netherlands Organisation
for Health Research and Development, and the Royal Netherlands Academy of Sciences.

Copyright © 2019 American Academy of Neurology

Access to Document

10.1212/WNL.0000000000007250

Cite this

Ferro, D. A., van den Brink, H., TRACE-VCI Study Grp, Exalto, L. G., Boomsma, J. M. F., Barkhof, F., Prins, N. D., van der Flier, W. M., Biessels, G. J., Benedictus, M. R., Bremer, J., Leijenaar, J., Tijms, B. M., Wattjes, M. P., Heringa, S. M., Kappelle, L. J., Reijmer, Y. D., Hamaker, M., Faaij, R., ... Koek, H. L. (2019). Clinical relevance of acute cerebral microinfarcts in vascular cognitive impairment. Neurology, 92(14), E1558-E1566. https://doi.org/10.1212/WNL.0000000000007250

@article{be00f4833a284a3e9402fb26f7c14baa,

title = "Clinical relevance of acute cerebral microinfarcts in vascular cognitive impairment",

abstract = "ObjectiveTo 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.MethodsThe 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 hyperintensitiesResultsA 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 beta-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).ConclusionIn 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.",

author = "Ferro, \{Doeschka A.\} and \{van den Brink\}, Hilde and \{TRACE-VCI Study Grp\} and Exalto, \{Lieza G.\} and Boomsma, \{Jooske M. F.\} and Frederik Barkhof and Prins, \{Niels D.\} and \{van der Flier\}, \{Wiesje M.\} and Biessels, \{Geert Jan\} and Benedictus, \{M. R.\} and J. Bremer and J. Leijenaar and Tijms, \{B. M.\} and Wattjes, \{M. P.\} and Heringa, \{S. M.\} and Kappelle, \{L. J.\} and Reijmer, \{Y. D.\} and M. Hamaker and R. Faaij and M. Pleizier and E. Vriens and Boss, \{H. M.\} and Weinstein, \{H. C.\} and P. Scheltens and Teunissen, \{C. E.\} and \{van den Berg\}, E. and O. Groeneveld and R. Heinen and J. Verwer and \{de Bresser\}, J. and Kuijf, \{H. J.\} and Koek, \{H. L.\}",

note = "Study funding The TRACE-VCI study is supported by Vidi grant 917.11.384 and Vici Grant 918.16.616 from ZonMw, the Netherlands, Organisation for Health Research and Development, and grant 2010T073 from the Dutch Heart Association to Geert Jan Biessels. Research of the Alzheimer Center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. The Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting VUmc fonds. The clinical database structure was developed with funding from Stichting Dioraphte. F. Barkhof is supported by the NIHR UCLH Biomedical Research Center. The authors also acknowledge support from the Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation (CVON 2012-06 Heart Brain Connection), Dutch Federation of University Medical Centres, the Netherlands Organisation for Health Research and Development, and the Royal Netherlands Academy of Sciences. Copyright {\textcopyright} 2019 American Academy of Neurology",

year = "2019",

month = apr,

day = "2",

doi = "10.1212/WNL.0000000000007250",

language = "English",

volume = "92",

pages = "E1558--E1566",

journal = "Neurology",

issn = "0028-3878",

publisher = "Lippincott Williams \& Wilkins",

number = "14",

}

Ferro, DA, van den Brink, H, TRACE-VCI Study Grp, Exalto, LG, Boomsma, JMF, Barkhof, F, Prins, ND, van der Flier, WM, Biessels, GJ, Benedictus, MR, Bremer, J, Leijenaar, J, Tijms, BM, Wattjes, MP, Heringa, SM, Kappelle, LJ, Reijmer, YD, Hamaker, M, Faaij, R, Pleizier, M, Vriens, E, Boss, HM, Weinstein, HC, Scheltens, P, Teunissen, CE, van den Berg, E, Groeneveld, O, Heinen, R, Verwer, J, de Bresser, J, Kuijf, HJ & Koek, HL 2019, 'Clinical relevance of acute cerebral microinfarcts in vascular cognitive impairment', Neurology, vol. 92, no. 14, pp. E1558-E1566. https://doi.org/10.1212/WNL.0000000000007250

TY - JOUR

T1 - Clinical relevance of acute cerebral microinfarcts in vascular cognitive impairment

AU - Ferro, Doeschka A.

AU - van den Brink, Hilde

AU - TRACE-VCI Study Grp

AU - Exalto, Lieza G.

AU - Boomsma, Jooske M. F.

AU - Barkhof, Frederik

AU - Prins, Niels D.

AU - van der Flier, Wiesje M.

AU - Biessels, Geert Jan

AU - Benedictus, M. R.

AU - Bremer, J.

AU - Leijenaar, J.

AU - Tijms, B. M.

AU - Wattjes, M. P.

AU - Heringa, S. M.

AU - Kappelle, L. J.

AU - Reijmer, Y. D.

AU - Hamaker, M.

AU - Faaij, R.

AU - Pleizier, M.

AU - Vriens, E.

AU - Boss, H. M.

AU - Weinstein, H. C.

AU - Scheltens, P.

AU - Teunissen, C. E.

AU - van den Berg, E.

AU - Groeneveld, O.

AU - Heinen, R.

AU - Verwer, J.

AU - de Bresser, J.

AU - Kuijf, H. J.

AU - Koek, H. L.

N1 - Study funding The TRACE-VCI study is supported by Vidi grant 917.11.384 and Vici Grant 918.16.616 from ZonMw, the Netherlands, Organisation for Health Research and Development, and grant 2010T073 from the Dutch Heart Association to Geert Jan Biessels. Research of the Alzheimer Center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. The Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting VUmc fonds. The clinical database structure was developed with funding from Stichting Dioraphte. F. Barkhof is supported by the NIHR UCLH Biomedical Research Center. The authors also acknowledge support from the Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation (CVON 2012-06 Heart Brain Connection), Dutch Federation of University Medical Centres, the Netherlands Organisation for Health Research and Development, and the Royal Netherlands Academy of Sciences. Copyright © 2019 American Academy of Neurology

PY - 2019/4/2

Y1 - 2019/4/2

N2 - ObjectiveTo 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.MethodsThe 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 hyperintensitiesResultsA 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 beta-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).ConclusionIn 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.

AB - ObjectiveTo 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.MethodsThe 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 hyperintensitiesResultsA 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 beta-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).ConclusionIn 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.

U2 - 10.1212/WNL.0000000000007250

DO - 10.1212/WNL.0000000000007250

M3 - Article

C2 - 30850444

SN - 0028-3878

VL - 92

SP - E1558-E1566

JO - Neurology

JF - Neurology

IS - 14

ER -

Clinical relevance of acute cerebral microinfarcts in vascular cognitive impairment

Abstract

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