Dementia with Lewy Bodies: Pathological Basis of the Cingulate Island Sign (P6.332)

OBJECTIVE: To investigate the clinical, imaging, and pathological associations of the cingulate island sign (CIS) in dementia with Lewy bodies (DLB). BACKGROUND: Clinical diagnosis of DLB remains suboptimal despite improved clinical criteria. Sparing of the posterior cingulate relative to the cuneus and precuneus (CIS), has been proposed as the [18F]2-fluoro-deoxy-D-glucose (FDG) PET biomarker to distinguish DLB from Alzheimer’s disease (AD), but the pathological basis of the sign is not known. DESIGN/METHODS: We retrospectively identified consecutive cases with a clinical diagnosis of DLB (n=39), and matched patients with AD (n=39) and cognitively normal subjects (n=78) who underwent FDG and 11C-Pittsburgh Compound-B (PiB) PET scans. We studied patients who came to autopsy (n=10) and underwent Braak-neurofibrillary tangle (NFT) staging. RESULTS: Subjects with a clinical diagnosis of DLB had a significantly higher CIS on FDG PET compared to AD subjects (p<0.001), which was independent of the presence of β-amyloid load on PiB PET (p=0.66). In the autopsy confirmed cases, 6/8 patients with a clinical diagnosis of DLB had intermediate or high likelihood DLB pathology and a positive CIS on visual assessment of FDG PET. 2/8 with a clinical DLB diagnosis but a negative CIS had AD pathology. CIS was negative in two patients with clinical diagnosis of AD, confirmed at autopsy. A higher CIS correlated with a lower Braak-NFT stage (r= -0.92; p<0.001). CONCLUSIONS: Our study finds that the presence of the CIS on FDG PET is not associated with β-amyloid load, but indicates a lower Braak-NFT stage in patients with DLB. Patients with a positive CIS fit into the high or intermediate probability DLB pathology group and are clinically diagnosed with DLB not AD. Identifying biomarkers which can measure relative contributions of underlying pathologies to a patient’s dementia is critical as neurotherapeutics moves towards targeted treatments. Study Supported by: AG040042/AG11378/AG16574/AG06786/Mangurian Foundation Disclosure: Dr. Graff-Radford has nothing to disclose. Dr. Murray has nothing to disclose. Dr. Lowe has received personal compensation for activities with Bayer Pharmaceuticals Corp. Dr. Lowe has received research support from GE Health Care, Siemens Molecular Imaging, and AVID Radiopharmaceuticals, Inc. Dr. Boeve has received research support from Cephalon, Inc., Allon Therapeutics, and GE Healthcare. Dr. Ferman has nothing to disclose. Dr. Przybelski has nothing to disclose. Dr. Lesnick has received personal compensation for activities with Reproductive Medicine and Infertility Associates as a consultant. Dr. Senjem has nothing to disclose. Dr. Gunter has nothing to disclose. Dr. Smith has nothing to disclose. Dr. Knopman has received personal compensation for activities with Eli Lilly & Company and TauRx Pharmaceuticals. Dr. Knopman has received personal compensation in an editorial capacity for Neurology. Dr. Knopman has received research support from Janssen and Baxter. Dr. Jack has received personal compensation for activities with Janssen, Eisai Inc., General Electric, Johnson & Johnson, and Eli Lilly & Co. Dr. Jack has received research support from Pfizer Inc., Allon, and Baxter. Dr. Dickson has received personal compensation for activities with Neotope, Inc. as a consultant. Dr. Petersen has received personal compensation for activities with Pfizer, Inc., and Janssen Alzheimer9s Immunotherapy. Dr. Petersen has received royalty payments from Oxford University Press. Dr. Kantarci has received research support from Pfizer Inc., Jannsen Alzheimer immunotherapy, and Takeda Global Research & Development Center.