Cerebrospinal Fluid Biomarkers and [11C]Pittsburgh Compound-B PET Concordance in Alzheimer Disease vs. Frontotemporal Dementia Syndromes (P1.213)

OBJECTIVE: To compare the rate of concordance between [ 11 C]Pittsburgh compound-B (PIB) PET and CSF biomarkers in clinical Alzheimer disease vs. frontotemporal dementia syndromes; and to analyze the discordant cases for which histopathology is available. BACKGROUND: Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD) can have clinically overlapping symptoms, and pathologically proven cases of each syndrome often meet the clinical criteria for the other (Varma et al 1999). Accurate differentiation of the two syndromes has important clinical and therapeutic implications. DESIGN/METHODS: We compared PIB-PET and CSF biomarker results in 78 patients (24 clinical AD syndromes, age:61.9±8.2, MMSE:23±7.2; 54 clinical FTD syndromes, age:63.8±8.7, MMSE:23±8.0) who underwent both tests within two years (mean 175±189 days). PET images were rated visually (+/-) blinded to diagnosis, and CSF biomarkers were rated as AD-like based on published threshold values (Shaw et al 2009). Twelve patients also underwent neuropathological examination (PET-autopsy interval: 2.6±1.6 years). RESULTS: PET was positive in 75[percnt] of patients with AD and in 13[percnt] of patients with FTD, while CSF tau:Aβ42 ratio was positive in 78[percnt] of AD and 17[percnt] of FTD patients. Of the CSF biomarkers, tau:Aβ42 ratio had the highest concordance with PET (87[percnt] agreement overall [kappa=0.71]; 91[percnt] agreement for AD subjects [κ=0.74]; 85[percnt] agreement for FTD subjects [κ=0.41]). In 5 of the 12 autopsy cases, PET and CSF tau:Aβ42 were both concordant with histopathologic results. Among the 7 discordant cases, one patient with a pathologic diagnosis of FTLD-TDP-U/MND was misclassified by both PET and CSF tau:Aβ42; and two patients with pathologically-confirmed FTLD (CBD and FTLD-TDP-B/MND) and CERAD frequent neuritic plaques (ADNC A2B1C3 and A1B1C3) were PIB-negative but had a CSF tau:Aβ42 in the AD range. CONCLUSIONS: Overall, PIB-PET and CSF biomarkers showed high concordance in classifying patients, though PET showed slightly better correlation with both clinical and pathological diagnoses. Disclosure: Dr. Bang has nothing to disclose. Dr. Ossenkoppele has nothing to disclose. Dr. Shaw has received personal compensation for activities with Innogenetics/Fujirebio, Janssen Pharmaceutica, and Saladax Biomedical. Dr. Miller has nothing to disclose. Dr. Seeley has nothing to disclose. Dr. Grinberg has nothing to disclose. Dr. Karydas has nothing to disclose. Dr. Boxer has received personal compensation for activities with Archer Pharmaceuticals, EnVivo Pharmaceuticals, Grifols, and iPerian as a consultant. Dr. Gorno Tempini has nothing to disclose. Dr. Trojanowski has received personal compensation for activities with Johnson & Johnson. Dr. Miller has received personal compensation in an editorial capacity for Cambridge University Press, Guilford Publications, Inc., and Neurocase. Dr. Jagust has received personal compensation for activities with Genentech Inc., Synarc, Janssen Alzheimer Immunotherapy, TauRx, and Siemens as a consultant. Dr. Rosen has nothing to disclose. Dr. Rabinovici has received personal compensation for activities with PCME/Rockpointe as a speaker. Dr. Rabinovici receives research support from the National Institutes of Health, Alzheimer9s Association, John Douglas French Alzheimer9s Foundation, Tau C