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August 26, 2014; 83 (9) Article

Dementia with Lewy bodies

Basis of cingulate island sign

Jonathan Graff-Radford, Melissa E. Murray, Val J. Lowe, Bradley F. Boeve, Tanis J. Ferman, Scott A. Przybelski, Timothy G. Lesnick, Matthew L. Senjem, Jeffrey L. Gunter, Glenn E. Smith, David S. Knopman, Clifford R. Jack, Dennis W. Dickson, Ronald C. Petersen, Kejal Kantarci
First published July 23, 2014, DOI: https://doi.org/10.1212/WNL.0000000000000734
Jonathan Graff-Radford
From the Departments of Neurology (J.G.-R., B.F.B., D.S.K., R.C.P.) and Radiology (V.J.L., C.R.J., K.K.), Division of Biomedical Statistics and Informatics (S.A.P., T.G.L.), and Departments of Information Technology (M.L.S., J.L.G.) and Psychiatry and Psychology (G.E.S.), Mayo Clinic, Rochester, MN; and Departments of Pathology and Laboratory Medicine (M.E.M., D.W.D.) and Psychiatry and Psychology (T.J.F.), Mayo Clinic, Jacksonville, FL.
MD
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Melissa E. Murray
From the Departments of Neurology (J.G.-R., B.F.B., D.S.K., R.C.P.) and Radiology (V.J.L., C.R.J., K.K.), Division of Biomedical Statistics and Informatics (S.A.P., T.G.L.), and Departments of Information Technology (M.L.S., J.L.G.) and Psychiatry and Psychology (G.E.S.), Mayo Clinic, Rochester, MN; and Departments of Pathology and Laboratory Medicine (M.E.M., D.W.D.) and Psychiatry and Psychology (T.J.F.), Mayo Clinic, Jacksonville, FL.
PhD
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Val J. Lowe
From the Departments of Neurology (J.G.-R., B.F.B., D.S.K., R.C.P.) and Radiology (V.J.L., C.R.J., K.K.), Division of Biomedical Statistics and Informatics (S.A.P., T.G.L.), and Departments of Information Technology (M.L.S., J.L.G.) and Psychiatry and Psychology (G.E.S.), Mayo Clinic, Rochester, MN; and Departments of Pathology and Laboratory Medicine (M.E.M., D.W.D.) and Psychiatry and Psychology (T.J.F.), Mayo Clinic, Jacksonville, FL.
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Bradley F. Boeve
From the Departments of Neurology (J.G.-R., B.F.B., D.S.K., R.C.P.) and Radiology (V.J.L., C.R.J., K.K.), Division of Biomedical Statistics and Informatics (S.A.P., T.G.L.), and Departments of Information Technology (M.L.S., J.L.G.) and Psychiatry and Psychology (G.E.S.), Mayo Clinic, Rochester, MN; and Departments of Pathology and Laboratory Medicine (M.E.M., D.W.D.) and Psychiatry and Psychology (T.J.F.), Mayo Clinic, Jacksonville, FL.
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Tanis J. Ferman
From the Departments of Neurology (J.G.-R., B.F.B., D.S.K., R.C.P.) and Radiology (V.J.L., C.R.J., K.K.), Division of Biomedical Statistics and Informatics (S.A.P., T.G.L.), and Departments of Information Technology (M.L.S., J.L.G.) and Psychiatry and Psychology (G.E.S.), Mayo Clinic, Rochester, MN; and Departments of Pathology and Laboratory Medicine (M.E.M., D.W.D.) and Psychiatry and Psychology (T.J.F.), Mayo Clinic, Jacksonville, FL.
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Scott A. Przybelski
From the Departments of Neurology (J.G.-R., B.F.B., D.S.K., R.C.P.) and Radiology (V.J.L., C.R.J., K.K.), Division of Biomedical Statistics and Informatics (S.A.P., T.G.L.), and Departments of Information Technology (M.L.S., J.L.G.) and Psychiatry and Psychology (G.E.S.), Mayo Clinic, Rochester, MN; and Departments of Pathology and Laboratory Medicine (M.E.M., D.W.D.) and Psychiatry and Psychology (T.J.F.), Mayo Clinic, Jacksonville, FL.
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Timothy G. Lesnick
From the Departments of Neurology (J.G.-R., B.F.B., D.S.K., R.C.P.) and Radiology (V.J.L., C.R.J., K.K.), Division of Biomedical Statistics and Informatics (S.A.P., T.G.L.), and Departments of Information Technology (M.L.S., J.L.G.) and Psychiatry and Psychology (G.E.S.), Mayo Clinic, Rochester, MN; and Departments of Pathology and Laboratory Medicine (M.E.M., D.W.D.) and Psychiatry and Psychology (T.J.F.), Mayo Clinic, Jacksonville, FL.
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Matthew L. Senjem
From the Departments of Neurology (J.G.-R., B.F.B., D.S.K., R.C.P.) and Radiology (V.J.L., C.R.J., K.K.), Division of Biomedical Statistics and Informatics (S.A.P., T.G.L.), and Departments of Information Technology (M.L.S., J.L.G.) and Psychiatry and Psychology (G.E.S.), Mayo Clinic, Rochester, MN; and Departments of Pathology and Laboratory Medicine (M.E.M., D.W.D.) and Psychiatry and Psychology (T.J.F.), Mayo Clinic, Jacksonville, FL.
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Jeffrey L. Gunter
From the Departments of Neurology (J.G.-R., B.F.B., D.S.K., R.C.P.) and Radiology (V.J.L., C.R.J., K.K.), Division of Biomedical Statistics and Informatics (S.A.P., T.G.L.), and Departments of Information Technology (M.L.S., J.L.G.) and Psychiatry and Psychology (G.E.S.), Mayo Clinic, Rochester, MN; and Departments of Pathology and Laboratory Medicine (M.E.M., D.W.D.) and Psychiatry and Psychology (T.J.F.), Mayo Clinic, Jacksonville, FL.
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Glenn E. Smith
From the Departments of Neurology (J.G.-R., B.F.B., D.S.K., R.C.P.) and Radiology (V.J.L., C.R.J., K.K.), Division of Biomedical Statistics and Informatics (S.A.P., T.G.L.), and Departments of Information Technology (M.L.S., J.L.G.) and Psychiatry and Psychology (G.E.S.), Mayo Clinic, Rochester, MN; and Departments of Pathology and Laboratory Medicine (M.E.M., D.W.D.) and Psychiatry and Psychology (T.J.F.), Mayo Clinic, Jacksonville, FL.
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David S. Knopman
From the Departments of Neurology (J.G.-R., B.F.B., D.S.K., R.C.P.) and Radiology (V.J.L., C.R.J., K.K.), Division of Biomedical Statistics and Informatics (S.A.P., T.G.L.), and Departments of Information Technology (M.L.S., J.L.G.) and Psychiatry and Psychology (G.E.S.), Mayo Clinic, Rochester, MN; and Departments of Pathology and Laboratory Medicine (M.E.M., D.W.D.) and Psychiatry and Psychology (T.J.F.), Mayo Clinic, Jacksonville, FL.
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Clifford R. Jack Jr
From the Departments of Neurology (J.G.-R., B.F.B., D.S.K., R.C.P.) and Radiology (V.J.L., C.R.J., K.K.), Division of Biomedical Statistics and Informatics (S.A.P., T.G.L.), and Departments of Information Technology (M.L.S., J.L.G.) and Psychiatry and Psychology (G.E.S.), Mayo Clinic, Rochester, MN; and Departments of Pathology and Laboratory Medicine (M.E.M., D.W.D.) and Psychiatry and Psychology (T.J.F.), Mayo Clinic, Jacksonville, FL.
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Dennis W. Dickson
From the Departments of Neurology (J.G.-R., B.F.B., D.S.K., R.C.P.) and Radiology (V.J.L., C.R.J., K.K.), Division of Biomedical Statistics and Informatics (S.A.P., T.G.L.), and Departments of Information Technology (M.L.S., J.L.G.) and Psychiatry and Psychology (G.E.S.), Mayo Clinic, Rochester, MN; and Departments of Pathology and Laboratory Medicine (M.E.M., D.W.D.) and Psychiatry and Psychology (T.J.F.), Mayo Clinic, Jacksonville, FL.
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Ronald C. Petersen
From the Departments of Neurology (J.G.-R., B.F.B., D.S.K., R.C.P.) and Radiology (V.J.L., C.R.J., K.K.), Division of Biomedical Statistics and Informatics (S.A.P., T.G.L.), and Departments of Information Technology (M.L.S., J.L.G.) and Psychiatry and Psychology (G.E.S.), Mayo Clinic, Rochester, MN; and Departments of Pathology and Laboratory Medicine (M.E.M., D.W.D.) and Psychiatry and Psychology (T.J.F.), Mayo Clinic, Jacksonville, FL.
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Kejal Kantarci
From the Departments of Neurology (J.G.-R., B.F.B., D.S.K., R.C.P.) and Radiology (V.J.L., C.R.J., K.K.), Division of Biomedical Statistics and Informatics (S.A.P., T.G.L.), and Departments of Information Technology (M.L.S., J.L.G.) and Psychiatry and Psychology (G.E.S.), Mayo Clinic, Rochester, MN; and Departments of Pathology and Laboratory Medicine (M.E.M., D.W.D.) and Psychiatry and Psychology (T.J.F.), Mayo Clinic, Jacksonville, FL.
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Citation
Dementia with Lewy bodies
Basis of cingulate island sign
Jonathan Graff-Radford, Melissa E. Murray, Val J. Lowe, Bradley F. Boeve, Tanis J. Ferman, Scott A. Przybelski, Timothy G. Lesnick, Matthew L. Senjem, Jeffrey L. Gunter, Glenn E. Smith, David S. Knopman, Clifford R. Jack, Dennis W. Dickson, Ronald C. Petersen, Kejal Kantarci
Neurology Aug 2014, 83 (9) 801-809; DOI: 10.1212/WNL.0000000000000734

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Abstract

Objectives: To investigate clinical, imaging, and pathologic associations of the cingulate island sign (CIS) in dementia with Lewy bodies (DLB).

Methods: We retrospectively identified and compared patients with a clinical diagnosis of DLB (n = 39); patients with Alzheimer disease (AD) matched by age, sex, and education (n = 39); and cognitively normal controls (n = 78) who underwent 18F-fluorodeoxyglucose (FDG) and C11 Pittsburgh compound B (PiB)-PET scans. Among these patients, we studied those who came to autopsy and underwent Braak neurofibrillary tangle (NFT) staging (n = 10).

Results: Patients with a clinical diagnosis of DLB had a higher ratio of posterior cingulate to precuneus plus cuneus metabolism, cingulate island sign (CIS), on FDG-PET than patients with AD (p < 0.001), a finding independent of β-amyloid load on PiB-PET (p = 0.56). Patients with CIS positivity on visual assessment of FDG-PET fit into the group of high- or intermediate-probability DLB pathology and received clinical diagnosis of DLB, not AD. Higher CIS ratio correlated with lower Braak NFT stage (r = −0.96; p < 0.001).

Conclusions: Our study found that CIS on FDG-PET is not associated with fibrillar β-amyloid deposition but indicates lower Braak NFT stage in patients with DLB. Identifying biomarkers that measure relative contributions of underlying pathologies to dementia is critical as neurotherapeutics move toward targeted treatments.

GLOSSARY

Aβ=
β-amyloid;
AD=
Alzheimer disease;
CERAD=
Consortium to Establish a Registry for Alzheimer's Disease;
CIS=
cingulate island sign;
DLB=
dementia with Lewy bodies;
DRS=
Mattis Dementia Rating Scale;
FDG=
18F-fluorodeoxyglucose;
NFT=
neurofibrillary tangle;
PiB=
Pittsburgh compound B;
ROI=
region of interest;
SPM=
Statistical Parametric Mapping;
UPDRS=
Unified Parkinson's Disease Rating Scale

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 December 27, 2013.
  • Accepted in final form May 17, 2014.
  • © 2014 American Academy of Neurology
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