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June 03, 2014; 82 (22) Article

Antemortem MRI findings associated with microinfarcts at autopsy

Mekala R. Raman, Gregory M. Preboske, Scott A. Przybelski, Jeffrey L. Gunter, Matthew L. Senjem, Prashanthi Vemuri, Matthew C. Murphy, Melissa E. Murray, Bradley F. Boeve, David S. Knopman, Ronald C. Petersen, Joseph E. Parisi, Dennis W. Dickson, Clifford R. Jack, Kejal Kantarci
First published May 2, 2014, DOI: https://doi.org/10.1212/WNL.0000000000000471
Mekala R. Raman
From the Departments of Neurology (M.R.R., B.F.B., D.S.K., R.C.P.), Radiology (G.M.P., J.L.G., M.L.S., P.V., M.C.M., C.R.J., K.K.), Health Sciences Research (S.A.P.), and Pathology (J.E.P.), Mayo Clinic, Rochester, MN; and Department of Neuroscience (M.E.M., D.W.D.), Mayo Clinic, Jacksonville, FL.
BS
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Gregory M. Preboske
From the Departments of Neurology (M.R.R., B.F.B., D.S.K., R.C.P.), Radiology (G.M.P., J.L.G., M.L.S., P.V., M.C.M., C.R.J., K.K.), Health Sciences Research (S.A.P.), and Pathology (J.E.P.), Mayo Clinic, Rochester, MN; and Department of Neuroscience (M.E.M., D.W.D.), Mayo Clinic, Jacksonville, FL.
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Scott A. Przybelski
From the Departments of Neurology (M.R.R., B.F.B., D.S.K., R.C.P.), Radiology (G.M.P., J.L.G., M.L.S., P.V., M.C.M., C.R.J., K.K.), Health Sciences Research (S.A.P.), and Pathology (J.E.P.), Mayo Clinic, Rochester, MN; and Department of Neuroscience (M.E.M., D.W.D.), Mayo Clinic, Jacksonville, FL.
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Jeffrey L. Gunter
From the Departments of Neurology (M.R.R., B.F.B., D.S.K., R.C.P.), Radiology (G.M.P., J.L.G., M.L.S., P.V., M.C.M., C.R.J., K.K.), Health Sciences Research (S.A.P.), and Pathology (J.E.P.), Mayo Clinic, Rochester, MN; and Department of Neuroscience (M.E.M., D.W.D.), Mayo Clinic, Jacksonville, FL.
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Matthew L. Senjem
From the Departments of Neurology (M.R.R., B.F.B., D.S.K., R.C.P.), Radiology (G.M.P., J.L.G., M.L.S., P.V., M.C.M., C.R.J., K.K.), Health Sciences Research (S.A.P.), and Pathology (J.E.P.), Mayo Clinic, Rochester, MN; and Department of Neuroscience (M.E.M., D.W.D.), Mayo Clinic, Jacksonville, FL.
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Prashanthi Vemuri
From the Departments of Neurology (M.R.R., B.F.B., D.S.K., R.C.P.), Radiology (G.M.P., J.L.G., M.L.S., P.V., M.C.M., C.R.J., K.K.), Health Sciences Research (S.A.P.), and Pathology (J.E.P.), Mayo Clinic, Rochester, MN; and Department of Neuroscience (M.E.M., D.W.D.), Mayo Clinic, Jacksonville, FL.
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Matthew C. Murphy
From the Departments of Neurology (M.R.R., B.F.B., D.S.K., R.C.P.), Radiology (G.M.P., J.L.G., M.L.S., P.V., M.C.M., C.R.J., K.K.), Health Sciences Research (S.A.P.), and Pathology (J.E.P.), Mayo Clinic, Rochester, MN; and Department of Neuroscience (M.E.M., D.W.D.), Mayo Clinic, Jacksonville, FL.
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Melissa E. Murray
From the Departments of Neurology (M.R.R., B.F.B., D.S.K., R.C.P.), Radiology (G.M.P., J.L.G., M.L.S., P.V., M.C.M., C.R.J., K.K.), Health Sciences Research (S.A.P.), and Pathology (J.E.P.), Mayo Clinic, Rochester, MN; and Department of Neuroscience (M.E.M., D.W.D.), Mayo Clinic, Jacksonville, FL.
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Bradley F. Boeve
From the Departments of Neurology (M.R.R., B.F.B., D.S.K., R.C.P.), Radiology (G.M.P., J.L.G., M.L.S., P.V., M.C.M., C.R.J., K.K.), Health Sciences Research (S.A.P.), and Pathology (J.E.P.), Mayo Clinic, Rochester, MN; and Department of Neuroscience (M.E.M., D.W.D.), Mayo Clinic, Jacksonville, FL.
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David S. Knopman
From the Departments of Neurology (M.R.R., B.F.B., D.S.K., R.C.P.), Radiology (G.M.P., J.L.G., M.L.S., P.V., M.C.M., C.R.J., K.K.), Health Sciences Research (S.A.P.), and Pathology (J.E.P.), Mayo Clinic, Rochester, MN; and Department of Neuroscience (M.E.M., D.W.D.), Mayo Clinic, Jacksonville, FL.
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Ronald C. Petersen
From the Departments of Neurology (M.R.R., B.F.B., D.S.K., R.C.P.), Radiology (G.M.P., J.L.G., M.L.S., P.V., M.C.M., C.R.J., K.K.), Health Sciences Research (S.A.P.), and Pathology (J.E.P.), Mayo Clinic, Rochester, MN; and Department of Neuroscience (M.E.M., D.W.D.), Mayo Clinic, Jacksonville, FL.
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Joseph E. Parisi
From the Departments of Neurology (M.R.R., B.F.B., D.S.K., R.C.P.), Radiology (G.M.P., J.L.G., M.L.S., P.V., M.C.M., C.R.J., K.K.), Health Sciences Research (S.A.P.), and Pathology (J.E.P.), Mayo Clinic, Rochester, MN; and Department of Neuroscience (M.E.M., D.W.D.), Mayo Clinic, Jacksonville, FL.
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Dennis W. Dickson
From the Departments of Neurology (M.R.R., B.F.B., D.S.K., R.C.P.), Radiology (G.M.P., J.L.G., M.L.S., P.V., M.C.M., C.R.J., K.K.), Health Sciences Research (S.A.P.), and Pathology (J.E.P.), Mayo Clinic, Rochester, MN; and Department of Neuroscience (M.E.M., D.W.D.), Mayo Clinic, Jacksonville, FL.
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Clifford R. Jack Jr
From the Departments of Neurology (M.R.R., B.F.B., D.S.K., R.C.P.), Radiology (G.M.P., J.L.G., M.L.S., P.V., M.C.M., C.R.J., K.K.), Health Sciences Research (S.A.P.), and Pathology (J.E.P.), Mayo Clinic, Rochester, MN; and Department of Neuroscience (M.E.M., D.W.D.), Mayo Clinic, Jacksonville, FL.
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Kejal Kantarci
From the Departments of Neurology (M.R.R., B.F.B., D.S.K., R.C.P.), Radiology (G.M.P., J.L.G., M.L.S., P.V., M.C.M., C.R.J., K.K.), Health Sciences Research (S.A.P.), and Pathology (J.E.P.), Mayo Clinic, Rochester, MN; and Department of Neuroscience (M.E.M., D.W.D.), Mayo Clinic, Jacksonville, FL.
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Full PDF
Citation
Antemortem MRI findings associated with microinfarcts at autopsy
Mekala R. Raman, Gregory M. Preboske, Scott A. Przybelski, Jeffrey L. Gunter, Matthew L. Senjem, Prashanthi Vemuri, Matthew C. Murphy, Melissa E. Murray, Bradley F. Boeve, David S. Knopman, Ronald C. Petersen, Joseph E. Parisi, Dennis W. Dickson, Clifford R. Jack, Kejal Kantarci
Neurology Jun 2014, 82 (22) 1951-1958; DOI: 10.1212/WNL.0000000000000471

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Abstract

Objective: To determine antemortem MRI findings associated with microinfarcts at autopsy.

Methods: Patients with microinfarcts (n = 22) and patients without microinfarcts (n = 44) who underwent antemortem MRI were identified from a dementia clinic–based, population–based, and community clinic–based autopsy cohort. The microinfarct and no-microinfarct groups were matched on age at MRI, age at death, sex, APOE status, Mini-Mental State Examination score, and pathologic diagnosis of Alzheimer disease. Brain infarcts were assessed on fluid-attenuated inversion recovery (FLAIR) MRI. White matter hyperintensities on FLAIR MRI and hippocampal volumes on T1-weighted MRI were quantified using automated methods. A subset of subjects with microinfarcts (n = 15) and a matched group of subjects without microinfarcts (n = 15) had serial T1-weighted MRIs and were included in an analysis of global and regional brain atrophy rates using automated methods.

Results: The presence of cortical (p = 0.03) and subcortical (p = 0.02) infarcts on antemortem MRI was associated with presence of microinfarcts at autopsy. Higher numbers of cortical (p = 0.05) and subcortical (p = 0.03) infarcts on antemortem MRI were also associated with presence of microinfarcts. Presence of microinfarcts was not associated with white matter hyperintensities and cross-sectional hippocampal volume on antemortem MRI. Whole-brain and regional precuneus, motor, and somatosensory atrophy rates were higher in subjects with microinfarcts compared to subjects without microinfarcts.

Conclusions: Microinfarcts increase brain atrophy rates independent of Alzheimer disease pathology. Association between microinfarct pathology and macroinfarcts on MRI suggests either common risk factors or a shared pathophysiology and potentially common preventive targets.

GLOSSARY

AD=
Alzheimer disease;
CAA=
cerebral amyloid angiopathy;
CERAD=
Consortium to Establish a Registry for Alzheimer's Disease;
FLAIR=
fluid-attenuated inversion recovery;
MPRAGE=
magnetization-prepared rapid-acquisition gradient echo;
MR=
magnetic resonance;
NFT=
neurofibrillary tangle;
ROI=
region of interest;
SPGR=
spoiled gradient recalled echo;
WMH=
white matter hyperintensity

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at Neurology.org

  • Received September 10, 2013.
  • Accepted in final form March 3, 2014.
  • © 2014 American Academy of Neurology
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