Pitie ´-Salpe ˆtrie `re, Paris, France; 2 CEA Service Hospitalier Frederic Joliot, Orsay, France. Contact e-mail: leocruzsouza@hotmail.com Background: The age of onset is a factor that influences the progression and severity of Alzheimer’s disease (AD). It is known that early onset AD (EOAD) evolves with a more rapid cognitive and functional decline than late onset AD (LOAD). The cause of this difference is not well known. Methods: We report two AD patients with the same educational level, but with different ages of onset of the disease. Mr C was 60 years old at the first visit and Mr W was 85 years old. Neither patient had familial history of AD. After 4 years of follow up, patients underwent 11 C Pittsburgh Compound B (PIB) positron emission tomography (PET). Results: At the first visit, both patients had preserved autonomy (CDR ¼ 0.5) and disease duration was similar (around 6 to 8 months). The MMSE score was lower for Mr C than for Mr W (24/30 and 27/30 respectively). Despite the same treatment (Rivastigmine), the cognitive decline was more rapid and more severe for Mr C than for Mr W. After 12 months of follow up, MMSE scores of Mr C and Mr W were 15/30 and 28/30 respectively and, after 30 months, they were 16/30 and 28/30, respectively. At the last visit, after 4 years of follow up, MMSE scores for Mr C and for Mr. W were 10/30 and 26/30, respectively and the CDR scores were 2 and 0.5, respectively. PIB Imaging [ 11 C]PIB-PET was then performed and prominent binding of PIB was ob- served in several cortical regions in both patients, in accordance with the di- agnosis. Surprisingly, PIB uptake in Mr C was 30 to 60 % more severe than for Mr W in all cortical regions (frontal, temporal, parietal and cingulate). Conclusions: We reported two patients with different forms of AD, regard- ing to the age of onset of the disease (EOAD vs LOAD). Both patients had similar clinical data for disease duration, disability at onset and treatment, but distinguished dramatically on the disease progression. PIB uptake in the EOAD patient was more severe than in LOAD case, suggesting that am- yloid load intensity could explain clinical differences between EOAD and LOAD. P2-378 CLINICAL AND QUANTITATIVE FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY IN PRESYMPTOMATIC AND SYMPTOMATIC PERSONS INHERITING FAMILIAL ALZHEIMER’S DISEASE MUTATIONS John M. Ringman 1 , Soo K. Lee 2 , Jorge Barrio 2 , Giovanni Coppola 2 , Gary Small 1 , Jeffrey L. Cummings 1 , Daniel H. Silverman 2 , 1 Easton Center for Alzheimer’s Disease Research at UCLA, Los Angeles, CA, USA; 2 Uni- versity of California, Los Angeles, Los Angeles, CA, USA. Contact e-mail: jringman@mednet.ucla.edu Background: Temporoparietal and posterior cingulate hypometabolism on fluorodeoxyglucose positron emission tomography (FDG-PET) is character- istic of Alzheimer’s disease (AD) and can precede symptoms. Persons inher- iting mutations causing familial AD (FAD) due to autosomal dominant mutations allow us to determine the earliest changes in cerebral metabolism occurring in the disease. Methods: Twenty-three persons with, or at-risk for inheriting FAD due to mutations in the PSEN1 or APP genes underwent clinical evaluations and FDG-PET scans. PET scans were clinically inter- preted in a blinded fashion. Genetic testing was performed and the number of subjects thought to have FDG-PET scans consistent with AD was com- pared between mutation carriers (MCs) and non-carriers (NCs). Regions of interest were defined and glucose uptake normalized to the pons and com- pared between MCs and a normative database. Results: 14 subjects were MCs (2 w/APP and 12 w/PSEN1 mutations) and 9 NCs. Mean age and age relative to the median age of AD diagnosis in the family ("adjusted age") did not differ statistically between MCs and NCs. Of the 14 MCs, 2 were demented, 2 were mildly impaired though not demented (CDR scores of 0.5), and the rest were asymptomatic (CDR ¼ 0). Nine of the 14 MCs and 1 of 9 NCs (age 43 years) were thought to have FDG-PET scans consistent with a neurodegenerative disorder (Fisher’s exact test, p ¼ 0.03). Three asymptomatic MCs whose anticipated age of diagnosis was more than 10 years away had scans consistent with AD. All but one of the MCs’ abnormal scans were also thought to demonstrate hypometabolism in primary visual cortex atypical for AD. When all MCs as a group were compared against a normative database, significant hypometabolism (-9 to -14%) was seen in the right and left posterior cingulate gyri, right lateral posterior temporal and parietotemporal, and primary visual cortices. Conclusions: FDG-PET can detect hypometabolism greater than 10 years prior to the anticipated age of dementia diagnosis in persons with FAD mutations. Hypometabolism in primary visual cortex atypical for AD is more common in this form of the disease. P2-379 (18)F-FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY IN PRESYMPTOMATIC PROGRANULIN MUTATION CARRIERS Itthipol Tawankanjanachot 1 , Claudia Jacova 1 , R. Hsiung Ging-Yuek 1 , Hyunsoo Steve Lee 1 , Siobhan McCormick 1 , Katie Dinelle 1 , Vesna Sossi 1 , Pheth Sengdy 1 , Rosa Rademakers 2 , Matthew C. Baker 2 , A. Jon Stoessl 1 , Howard H. Feldman 1 , Ian R. Mackenzie 1 , 1 University of British Columbia, Vancouver, BC, Canada; 2 Mayo Clinic, Jacksonville, FL, USA. Contact e-mail: dritthipol@hotmail.com Background: Mutations in the progranulin (GRN) gene are a cause of FTLD with ubiquitin/TDP-43-immunoreactive neuronal inclusions (FTLD-TDP). Asymmetric atrophy patterns are reported in FTLD resulting from GRN mu- tations following symptom onset. There are no published neuroimaging stud- ies of GRN mutation carriers prior to symptom onset. We investigated whether there are early FDG-PET metabolic abnormalities in presymptom- atic family members within kindreds having GRN mutations, by comparing the (18)F-FDG uptake of those positive for GRN mutation (carriers) with those negative for GRN mutation (non-carriers) in the same kindreds. Methods: Members from three families with pathologically-confirmed FTLD-TDP GRN-mutation positive probands were screened for gene muta- tions, scanned with MRI and (18)F-FDG PET. Thirteen bilateral 8-mm re- gions of interest (ROIs) were placed on MRI template using the Brodmann MRIcron atlas, then adjusted and applied to co-registered individual MRI/ PET. (18)F-FDG uptake was calculated as the ratio of ROI to pons. An- tero-posterior, dorsal-ventral, and left-right asymmetry indices were com- puted as the ratio of first to second. ANCOVA adjusted for sex was used to compare carriers to non-carriers, ROC to evaluate discriminative power. Results: There were 7 carriers (6 females, 1 male, age M ¼ 53.2 6 14.5, MMSE M ¼ 28.1 6 2.8, FAB M ¼ 17.3 6 1.0) and 9 non-carriers (4 fe- males, 5 males. age M ¼ 53.8 6 8.5, MMSE M ¼ 29.5 6 0.8, FAB ¼ M17.5 6 0.5). The anterior-posterior asymmetry index was significantly lower in carriers than non-carriers (M ¼ .0.79 6 0.11, vs. M ¼ 0.91 6 0.08, p ¼ .026). This asymmetry was more pronounced in the left (p ¼ .011) than in the right isocortex (p ¼ .092). ROIs with significantly lower up- take in carriers were in the anterior cingulate, anterior insula and temporal pole. On ROC, left anterior-posterior asymmetry discriminated between car- riers and non-carriers with AUC ¼ 0.86, specificity ¼ 86%, sensitivity ¼ 67%. All anterior cortical ROIs showed strong inverse correlations with age in carriers (Pearson’s r range -.6 to -.9) but not non-carriers. Dorsal-ven- tral and left-right asymmetry indices did not differentiate carriers and non- carriers. Conclusions: There appears to be a footprint of FTLD-TDP associ- ated with GRN mutations prior to symptom onset, with reduced PET glucose uptake in left anterior cortical regions. This finding has implications regard- ing the timing of pathological events, their treatment when available, and the potential utility of PET as a biomarker. P2-380 EFFECT OFAPOE4 STATUS AND ALZHEIMER’S DISEASE ON POSTERIOR CINGULATE CONNECTIVITY Mary M. Machulda 1 , David T. Jones 1 , Eric M. McDade 1 , Prashanthi Vemuri 1 , Ramesh Avula 1 , Scott A. Przybelski 1 , Steven Younkin 2 , Matt Senjem 1 , Jeff Gunter 1 , Brad Boeve 1 , David Knopman 1 , Ronald C. Petersen 1 , Clifford R. Jack 1 , 1 Mayo Clinic, Poster Presentations P2 S427