Jonathan Graff-Radford1, Melissa E Murray1, Val J Lowe1, Bradley F Boeve1, Tanis J Ferman1, Scott A Przybelski1, Timothy G Lesnick1, Matthew L Senjem1, Jeffrey L Gunter1, Glenn E Smith1, David S Knopman1, Clifford R Jack1, Dennis W Dickson1, Ronald C Petersen1, Kejal Kantarci2. 1. 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. 2. 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. kantarci.kejal@mayo.edu.
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.
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.
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