Carole Azuar

Testing the model of caudo-rostral organization of cognitive control in the human with frontal lesions.

The cascade model of cognitive control, mostly relying on functional neuroimaging studies, stipulates that the lateral frontal cortex (LFC) is organized as a cascade of executive processes involving three levels of cognitive control, implemented in distinct LFC areas from the premotor to the anterior prefrontal regions. The present experiment tested this model in patients with LFC lesions and studied the hierarchy of executive functions along the caudo-rostral axis, i.e. the respective roles of the different LFC areas in the control of behavior. Voxel-based lesion-symptom mapping and region of interest group analyses were conducted in 32 patients with focal LFC lesions who performed cognitive tasks assessing the cascade model. We first showed that three different LFC areas along the caudo-rostral axis subserved three distinct control levels, whose integrity is necessary for adaptive behavior. Second, we found that prefrontal cognitive control has an asymmetric organization: higher control processes involving more anterior prefrontal regions rely on the integrity of lower control processes in more posterior regions, while lower control processes can operate irrespective of the integrity of higher control processes. Altogether, these findings support a caudo-rostral cascade of executive processes from premotor to anterior prefrontal regions.

White matter lesions in FTLD: distinct phenotypes characterize GRN and C9ORF72 mutations

Frontotemporal lobar degeneration (FTLD) has a high frequency of genetic forms; the 2 most common are GRN (progranulin) and C9ORF72 mutations. Recently, our group reported extensive white matter (WM) lesions in 4 patients with FTLD caused by GRN mutation, in the absence of noteworthy cardiovascular risk factors,1 in line with other studies in GRN mutation carriers.2,3 Here we compared the characteristics of frontal WM lesions in patients with behavioral variant of FTLD (bv-FTLD) caused by GRN and C9ORF72 mutations.

Paris: A new comprehensive language tool for the diagnosis and categorization of primary progressive aphasia

otherwise undetectable cognitive deficits in preclinical AD. We aimed to compare the effects of low-dose (0.20mg s.c.) scopolamine on cognition between Ab+ and AbCN older adults using the Groton Maze Learning Task (GMLT). Methods: Cognitively normal (CN) older adults (n1⁄463), with a family history of AD and subjective memory complaints, completed the GMLT predose, and then received low-dose scopolamine (0.20 mg) subcutaneously. Participants were re-assessed 1-, 3-, 5-, 7-, and 8hours post-dose. All participants underwent positron emission tomography (PET) neuroimaging for Ab using F-florbetapir within 6 weeks of their baseline visit. Fifteen CN older adults were classified as Ab+ and 48 were classified as Ab-. Results: At 5-hours post-dose, the Ab+ group performed significantly worse than the Abgroup on all measures of learning efficiency and working memory/executive function (Cohen’s d1⁄41.13-1.56). When participants were classified as having an abnormal response to scopolamine (based on change score at 5-hours post-dose greater than zero), 100% were correctly classified as Ab+ and 67% as Ab-. Conclusions: Depletion of cortical cholinergic neurotransmission is a characteristic feature of AD, and may be mechanistically related to Ab-related disruption to the cholinergic system. In individuals at risk for AD (e.g., individuals with MCI), or who later progress to AD, neurodegenerative changes are evident within the basal forebrain cholinergic system and the nucleus basalis of Meynert (NbM). Results of this study suggest that diminished cholinergic tone likely also occurs in preclinical AD, and as such, the use of a cholinergic stress test to perturb an already compromised neurotransmitter system may be an effective way of identifying CN older adults with substantial neocortical beta-amyloid aggregation and who are in the preclinical stage of AD.

First European case of Creutzfeldt-Jakob disease with a PRNP G114V mutation

Genetic Creutzfeldt-Jakob disease is due to mutations in the PRNP gene. Only two families with a PRNP G114V mutation have been described around the world. We report the first European case, who had no family history and initially presented with isolated deficit in hippocampus-dependent memory. Initial investigations were normal except for elevated total tau protein in the cerebrospinal fluid. He died 4 years after disease onset. This case highlights the diagnostic difficulties posed by genetic Creutzfeldt-Jakob disease, and shows that genetic analyses should be considered even in sporadic cases.

THE MINI EATING BEHAVIOR INVENTORY (MINI EBI): A 10-ITEM CLINICAL TOOL FOR THE EARLY DIAGNOSIS OF FRONTOTEMPORAL DEMENTIA

Background: In order to be helpful for the diagnosis and prediction of the shunting surgery outcome in Chinese idiopathic normal pressure hydrocephalus patients, we herein were to explore the correlation between the clinical, neuroimaging characteristics and the cerebrospinal fluid tap test response. Methods: 43 iNPH patients in PUMCH from 2013-2015 were included. All patients were evaluated using MMSE, MOCA, ADL, iNPH scale, underwent 1.5T head MRI scan and a cerebrospinal fluid tap with removal of 30 ml of CSF .The evaluations prior to and posterior to CSF tap test included the 10m walking time and steps, TMT-A, digital symbol and STROOP test. Two experienced neurologists were responsible for the adjustment of the CSF tap test response. The clinical and neuroimaging parameters of iNPH patients were analyzed between the CSF tap test responders and non-responders. Results:Compared with non-responders, the patients of CSF tap test responders had more male patients (male: female 20:4 vs. 9:10, p1⁄4 0.021), longer walking disturbance history ((1040.136708.33) days vs. (597.066527.7) days, p1⁄4 0.035), lower baseline cognitive tests z score (-15.731616.537 vs. -4.23668.280, p1⁄4 0.041) and more periventricular white matter lesions (p1⁄4 0.033). Conclusions: We report some clinical and neuroimaging characters of iNPH patients which were a little different from those have been reported. Our limitation is that the shunting result hadn’t been analyzed because of the limited number of patients. However the results indicated that the patients with the longer duration, the lower cognitive tests score and the prominent white matter lesions should not be excluded for the shunting surgery.

THE MORAL EMOTIONS ASSESSMENT: A NEW TOOL FOR THE EARLY DIAGNOSIS OF FRONTOTEMPORAL DEMENTIA

TOOL FOR THE EARLY DIAGNOSIS OF FRONTOTEMPORAL DEMENTIA Carole Azuar, Chlo e Daigmorte, Maeva Camus, Thomas Mauras, Aurelie Funkiewiez, Isabelle Le Ber, Bruno Dubois, Richard Levy, Marc Teichmann, APHPGroupe Hospitalier Pitie Salpetriere, Paris, France; 2 INSERMUniversite Pierre et Marie Curie, Paris 6, IHU-ICM, Paris, France; Centre Hospitalier Sainte Anne, Paris, France; APHP-Groupe Hospitalier Pitie Salpetriere, Paris, France; INSERMUniversit e Pierre et Marie Curie, Paris 6, IHU-ICM, Paris, France. Contact e-mail: carole.azuar@gmail.com

Last and art aphasia screening tools: Switching context from stroke to neurodegenerative diseases

correlated with AAO in the PCA patients. Results:Early onset PCA was associated with lower cortical thickness bilaterally in the inferior parietal lobe, angular gyrus and precuneus, whilst late onset PCAwas associated with lower thickness in frontal and medial temporal lobe regions (Figure 1). Consistent with the imaging findings, early onset PCA was associated with worse performance on digit span (0.53, p 1⁄4 0.001), calculation (0.48, p 1⁄4 0.003) and spelling (0.29, p1⁄4 0.026) all of them tests associated with dominant parietal function. Conclusions: Our data suggest that early-onset PCA patients have a greater involvement of bilateral (especially dominant) posterior cortices, and question the factors driving the relationship between age at onset and phenotypic heterogeneity not just between but also within the recognised atypical AD phenotypes.