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International audience; We report the case of a 37-year-old man suffering from insidious visual agnosia and spastic paraparesis due to a PSEN1 mutation. His mother was diagnosed with Alzheimer disease after a biopsy. He was assessed by multimodal neuroimaging, including new in vivo positron emission tomography amyloid imaging (F-AV45). His data were compared with those from healthy participants and patients with sporadic predemential Alzheimer disease. He exhibited posterior cortical thickness reduction, posterior hypometabolism, and increased amyloid ligand uptake in the posterior cortex and the striatum. We show that F-AV45 positron emission tomography allows visualization of the unusual pattern of amyloid deposits that co-localize with cortical atrophy in this genetic form of Alzheimer disease.

Background and Purpose— Very few neuroimaging studies have focused on follow-up of subcortical aphasia. Here, overt language production tasks were used to correlate regional cerebral blood flow (rCBF) changes and language performance in patients with vascular subcortical lesions. Methods— Seven aphasic patients were scanned twice with positron emission tomography (PET) at 1-year interval during a word-generation task. Using SPM2, Language-Rest contrast at PET1 was correlated to language performance and to time-lag from stroke. The same contrast was performed at PET2 and session effect (PET2–PET1) was correlated with performance improvement. Results— At PET1, correlation between rCBF and delay from stroke involved mainly ventral regions of the left temporal cortex and mesial frontal cortex. Correlations between rCBF and performance showed predominantly left dorsal regions in the frontal, temporal, and parietal lobes, but also the left ventral temporal cortex. One year apart, language performance improved and rCBF increased in perisylvian regions bilaterally. Best performers at PET2 showed an increase of activity in left ventral temporal cortex as well as in right middle temporal gyrus. Conclusions— On follow-up, expected language improvement and increase of activation in the classical language areas and their counterparts were observed. Moreover, all correlational analyses both at PET1 and on follow-up implicated the anterior part of the left inferior temporal gyrus, suggesting a disconnection between the superior and inferior parts of the left temporal cortex and a specific role for this region in lexical semantic processing.

Background and Purpose— Follow-up neuroimaging studies of aphasia never addressed a comparison between aphasic and healthy subjects. Investigation of changes over time in healthy subjects during language tasks seems a prerequisite before interpretation of longitudinal changes in aphasic patients. Methods— Six healthy subjects and 8 aphasic patients were PET scanned twice (PET1 and PET2) at a 1-year interval during a word generation task. Using SPM99, language-rest main effect was compared at PET1 and PET2 in each group, whereas group effect was assessed at each session. Correlations were analyzed in each group between performance indexes and changes in regional cerebral flood flow (rCBF) between the 2 sessions. Results— Language performances were improved in both groups. rCBF decreased from PET1 to PET2 in the healthy group and increased in the aphasic group in perisylvian regions bilaterally. Correlations between performance and rCBF changes across sessions were similar in the 2 groups; positive correlations involved superior temporal cortexes bilaterally, and negative correlations concerned superior frontal and medial temporal regions. Conclusions— Increased perisylvian activation over time probably reflects improved performance at the expenses of cognitive effort in aphasic patients. Decreased activation in different neural systems suggests a familiarization effect with reduced emotional load.

Objective: To determine the value of clinical assessment, MRI cortical thickness and [18FDG]-PET metabolism in predicting pathophysiology defined by cerebro-spinal fluid (CSF) biomarkers in patients suffering of predominant language difficulties of a neurodegenerative origin. Background Aphasia is common in neurodegenerative diseases, and may be the main symptom, as in all 3 variants of progressive primary aphasia (PPA). Some studies have tried to predict the underlying pathology. Each variant is associated with a predominant histopathology, but it can only reflect group-wide probabilities. We decided to consider the underlying pathology (Alzheimer9s (AD) or non-AD), and check subsequently if any clinical, structural or metabolic differences could emerge between both defined groups. Design/Methods: 26 aphasic patients underwent comprehensive language and neuropsychological assessments, structural MRI, [18FDG]-PET, and CSF analysis; eleven age-matched healthy controls (HC) underwent the same examinations except for the lumbar puncture. Biomarkers in CSF allowed us to classify patients as AD or non-AD. Results: 11 subjects had biomarkers consistent with AD, leaving 15 in the non-AD group. Compared to the HC, language impairment was the main symptom for all patients. However, no differences between groups emerged in language assessments. AD patients exhibit more praxis and visuo-spatial difficulties compared to the non AD group. The difference was significant but less marked for memory. MRI showed more posterior and symmetric cortical thickness reduction in the AD group. No difference in the medial temporal lobe was observed between the two patients groups. Temporo-parietal hypometabolism was more marked in the AD group but no difference in frontal cortex was found. Conclusions: Language impairment is not a reliable predictor of pathology in our patients, though it is the main symptom. Clinical presentation seems to depend on anatomic damage sites more than the underlying pathology. Disclosure: Dr. Sagot has nothing to disclose. Dr. Saint-Aubert has nothing to disclose. Dr. Bezy has nothing to disclose. Dr. Mirabel has nothing to disclose. Dr. Payoux has nothing to disclose. Dr. Dumas has nothing to disclose. Dr. Vincent has nothing to disclose. Dr. Peran has nothing to disclose. Dr. Barbeau has nothing to disclose. Dr. Puel has nothing to disclose. Dr. Chollet has nothing to disclose. Dr. Pariente has nothing to disclose.

Objective: To evaluate the frequency of c9ORF72 repeat expansion in french FTLD and FTLD-ALS patients and to describe the associated clinical phenotypes, imaging and brain pathological characteristics. Background c9ORF72 was recently identified as a major gene implicated in FTLD/ALS spectrum of disease. Its genetic contribution remains to be established in different geographic populations. Design/Methods: c9ORF72 repeat expansion was searched for by repeat-primed PCR in 600 french probands with frontal variant FTD (fvFTD, n=330), FTLD with amyotrophic lateral scelrosis (FTLD-ALS, n=210), primary progressive aphasia (PPA, n=40) and progressive supranuclear palsy (PSP, n=20). Half patients had a family history of FTLD or ALS, half were sporadic cases. Brain post-mortem examination was performed in 18 patients. Results: A GGGGCC repeat expansion was identified in 140 unrelated probands. The frequency of the expansion was 15% in the patients with bvFTD (8% in sporadic cases, 20% in familial bvFTD)and 43% in the patients with FTLD-ALS (15% in sporadic cases; 64% in familial forms). No expansion was identified in the PPA patients. Most patients had a bvFTD; only two patients presented with semantic dementia or progressive non fluent aphasia both associated with ALS at onset. The detailed clinical phenotypes, SPECT imaging characteristics and pathology of 60 c9ORF72 expansion carriers will be presented. Conclusions: c9ORF gene is the most frequent cause of familial FTLD before PGRN gene. The frequency of mutation is much higher in the population with FTLD-ALS. Less than 30% of familial FTLD/FTLD-ALS are unexplained by the eight known FTLD genes. Disclosure: Dr. Le Ber has nothing to disclose. Dr. Camuzat has nothing to disclose. Dr. Guillot-Noel has nothing to disclose. Dr. Guedj has nothing to disclose. Dr. Hannequin has nothing to disclose. Dr. Wargon has nothing to disclose. Dr. Couratier has nothing to disclose. Dr. Deramecourt has nothing to disclose. Dr. Berger has nothing to disclose. Dr. Viennet has nothing to disclose. Dr. Pasquier has nothing to disclose. Dr. Lacomblez Aurousseau has nothing to disclose. Dr. Salachas has nothing to disclose. Dr. Martinaud has nothing to disclose. Dr. Golfier has nothing to disclose. Dr. Puel has nothing to disclose. Dr. Vercelletto has nothing to disclose. Dr. Didic has nothing to disclose. Dr. Sauvee has nothing to disclose. Dr. Sellal has nothing to disclose. Dr. Thomas-Anterion has nothing to disclose. Dr. Campion has nothing to disclose. Dr. Michel has nothing to disclose. Dr. Dubois has received personal compensation for activities with Bristol-Myers Squibb, Roche, Elan, Eli Lilly, Eisai, and Janssen as a consultantDr. Dubois has received personal compensation for serving on the advisory board of Bristol-Myers Squibb, Roche, Elan, Eli Lilly, Eisai, and Janssen.Dr. Dubois has received research support from Novartis and Sanofi-Aventis. Dr. Camu has nothing to disclose. Dr. Seilhean has nothing to disclose. Dr. Meininger has received personal compensation for activities with Servier and GlaxoSmithKline. Dr. Habert has nothing to disclose. Dr. Duyckaerts has nothing to disclose. Dr. Brice has nothing to disclose.