FINAL PROGRAM AND ABSTRACT BOOK

A satellite symposium held during the 21st ENS meeting“Advances in frontotemporal dementias”Lisbon, Portugal - May 30, 2011

General Information

VenueThe symposium will take place at the:

Lisboa Convention Centre Praça das Indústrias1300-307 Lisbon - Portugalwww.lisboacc.pt

LanguageThe official language of the symposium will be English.

LocationLisbon is offering a fascinating combination of the old and the new, with an unmistakable character and a beauty all of its own. Thecradle of the city is the medieval castle of Sao Jorge, which stands with its ten towers on the hill. Nearby is Alfama, the old Moorishquarter with its narrow winding streets and white washed houses and the Bairro Alto, center of fado, the traditional folksong ofLisbon. Belem - where the ships of Vasco da Gama and other famous explorers were launched from, with its famous Tower and theMonastery of Geronimo's, both among the finest examples of Manueline Architecture. Beautiful works of Art may be admired inMuseums and Palaces all over Lisbon.

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“Advances in frontotemporal dementias”A satellite symposium held during the 21st European Neurological Society (ENS) meeting

Serono Symposia International Foundation symposium on:

Advances in frontotemporal dementiasLisbon, Portugal - May 30, 2011

Aim of the symposiumFrontotemporal dementia (FTD) is the second most common early-onset dementia after Alzheimer's disease. The Serono SymposiaInternational Foundation satellite symposium at ENS Meeting will provide a comprehensive overview of pathogenetic mechanisms,diagnostic tools and phenoptypes in this increasingly relevant neurodegenerative condition.

Learning objectivesAt the end of this symposium participants will have:• A review of the most relevant pathogenetic mechanisms of FTD• An update on MRI diagnostic criteria • An overview of the clinical heterogeneity

Target audienceScientists, clinicians, biologists, working in the field of neurology, will benefit from this symposium.

AccreditationSerono Symposia International Foundation (www.seronosymposia.org) has submitted this program “Advances in frontotemporaldementias” (Lisbon, Portugal - May 30, 2011) for accreditation by the Royal College of Physician (RCP).

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All Serono Symposia International Foundation programs are organized solely to promote the exchange and dissemination of scientific and medical information.No forms of promotional activities are permitted. There may be presentations discussing investigational uses of various products. These views are theresponsibility of the named speakers, and do not represent an endorsement or recommendation on the part of Serono Symposia International Foundation. Thisprogram is made possible thanks to unrestricted educational grants received from: Centre d’Esclerosi Multiple de Catalunya, ComtecMed, Congrex Sweden,Congrex Switzerland, Cryo-Save, Datanalysis, Esaote, European Society of Endocrinology, Fundación IVI, ISFP International Society for Fertility Preservation, ISMHInternational Society of Men’s Health, K.I.T.E., Merck Serono, Ministry of Health of the State of Israel, University of Catania, Vall d'Hebron University Hospital.

List of speakers and chairmen

ChairGiancarlo ComiDepartment of NeurologyInstitute of Experimental NeurologyVita-Salute San Raffaele UniversityMilan, Italy

Co-ChairStefano F. CappaDepartment of Neuroclinical SciencesVita Salute University and San Raffaele Scientific InstituteMilan, Italy

Scientific secretariatSerono Symposia International FoundationSalita di San Nicola da Tolentino, 1/b00187 Rome, Italy

Associate project manager: Luisa RinaldiTel.: +39-06-420 413 314Fax: +39-06-420 413 677E-mail: info@seronosymposia.org

Serono Symposia International Foundation is a Swiss Foundation with headquarters in 14, rue du Rhône, 1204 Geneva, Switzerland

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List of speakers and chairmenFederica AgostaNeuroimaging Research UnitIRSPE, Division of NeuroscienceScientific Institute and University Hospital San RaffaeleMilan, Italy

Stefano F. CappaDepartment of Neuroclinical SciencesVita Salute University and San Raffaele Scientific InstituteMilan, Italy

Giancarlo ComiDepartment of NeurologyInstitute of Experimental NeurologyVita-Salute San Raffaele UniversityMilan, Italy

David MannMental Health andNeurodegeneration Research GroupSchool of Community Based MedicineUniversity of ManchesterHope HospitalStott Lane, Salford, UK

Scientific ProgramMonday – May 30, 2011

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11.45 Serono Symposia International Foundation (SSIF) OpeningGiancarlo Comi, Italy

11.55 Welcome and IntroductionStefano Cappa, Italy

12.00 L1: Pathological and molecular genetic correlatesDavid Mann, UK

12.25 L2: Role of the MRI in the diagnosisFederica Agosta, Italy

12.50 L3: Clinical heterogeneityStefano Cappa, Italy

13.15 Concluding remarksGiancarlo Comi, Italy - Stefano Cappa, Italy

Disclosure of faculty relationships

Serono Symposia International Foundation adheres to guidelines of the European Accreditation Council for Continuing MedicalEducation (EACCME) and all other professional organizations, as applicable, which state that programs awarding continuingeducation credits must be balanced, independent, objective, and scientifically rigorous. Investigative and other uses forpharmaceutical agents, medical devices, and other products (other than those uses indicated in approved product labeling/packageinsert for the product) may be presented in the program (which may reflect clinical experience, the professional literature or otherclinical sources known to the presenter). We ask all presenters to provide participants with information about relationships withpharmaceutical or medical equipment companies that may have relevance to their lectures. This policy is not intended to excludefaculty who have relationships with such companies; it is only intended to inform participants of any potential conflicts soparticipants may form their own judgments, based on full disclosure of the facts. Further, all opinions and recommendationspresented during the program and all program-related materials neither imply an endorsement, nor a recommendation, on the partof Serono Symposia International Foundation. All presentations solely represent the independent views of the presenters/authors.

The following faculty provided information regarding significant commercial relationships and/or discussions of investigational ornon-EMEA/FDA approved (off-label) uses of drugs:

Federica Agosta Declared no potential conflict of interest.

Stefano F. Cappa Declared no potential conflict of interest.

Giancarlo Comi Declared receipt of honoraria or consultation fees from Serono Symposia International Foundation, MerckSerono, Sanofi Aventis, Novartis, Biogen, Dompè, Bayer Schering, Teva Pharmaceuticals Ltd.

David Mann Declared no potential conflict of interest.

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Abstracts

L1 - Pathological and molecular genetic correlates

Frontotemporal lobar degeneration (FTLD) encompasses a number of neurodegenerative diseases that affect the frontal andtemporal lobes. It is the second most common neurodegenerative cause of dementia after Alzheimer’s Disease in the presenium,with a prevalence of 15 cases per 100,000. Both men and women are affected equally, with up to 40% of patients reporting a familyhistory of the disease in at least one first degree relative. There are 3 major clinical syndromes: frontotemporal dementia (FTD), withchanges in personal and social behaviour, semantic dementia (SD) with fluent aphasia, and primary progressive non-fluent aphasia(PNFA). Some patients exhibit parkinsonism, and about 10% cases additionally show clinical symptoms of motor neuron disease(MND). FTLD is also pathologically heterogeneous. About 45% cases are associated with tauopathy (FTLD-tau), with about half suchcases having Pick bodies and Pick cells (Pick’s Disease) and half being associated with a mutation in tau gene (MAPT), showing Pickbody- or neurofibrillary tangle- like structures in neurones and/or glial cells. Most remaining cases are characterized by neuronalinclusion bodies (NCI) composed of phosphorylated TAR-DNA-binding protein 43 (TDP-43), and are known as FTLD-TDP. Lesscommon are cases with inclusions containing Fused in Sarcoma protein (FUS), and termed FTLD-FUS, or containing unidentifiedubiquitinated NCI and called FTLD-UPS. FTLD-TDP is classified into four subtypes. Type 1 has many dystrophic neurites (DN) withfew NCI and no neuronal intranuclear inclusions (NII) and is associated with SD. Type 2 has many NCI with few DN and no NII andis associated with FTLD and MND. Many such cases are linked to a yet unidentified genetic locus on chromosome 9p. Type 3 hasmany NCI and DN and infrequent NII and is associated with FTD or PNFA. Many such cases show mutations in progranulin (GRN),which lead to reductions in progranulin in plasma. Measuring this can be used as a screening tool for the detection of suchmutations. Type 4 has numerous NII but few DN and NCI and is associated with mutations in vasolin containing protein (VCP). Thereare three subtypes of FTLD-FUS: atypical FTLD-U (aFTLD-U), Basophilic Inclusion Body Disease (BIBD) and Neuronal IntermediateFilament Inclusion body Disease (NIFID). FTLD-UPS cases are mostly caused by mutations in the CHMP2B gene, and result in NCInegative for tau and TDP-43 but immunoreactive for ubiquitin and p62.

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David MannMental Health and Neurodegeneration Research Group, School of Community Based Medicine, University of Manchester,Hope Hospital, Stott Lane, Salford, UK

L2 - Role of the MRI in the diagnosis

The clinical use of magnetic resonance imaging (MRI) has dramatically improved our ability to diagnose dementia accurately,including frontotemporal dementia (FTD). Despite variation and overlap of atrophy patterns, the assessment of regional atrophy onstructural MRI scans holds promise in discriminating FTD from Alzheimer’s disease (AD). Recent years have also witnessedimpressive improvements in the use of advanced MR techniques, including diffusion tensor (DT) MRI and functional MRI (fMRI), inpatients with dementia with the aim of ameliorating the diagnostic work up as well as to monitor disease progression. In a recentstudy comparing behavioural variant FTD (bvFTD) with AD, it was shown that bvFTD is associated with a greater reduction of whitematter (WM) integrity in frontal brain regions, whereas no WM areas in AD showed greater damage than in bvFTD. A seminal restingstate fMRI study suggests that bvFTD and AD target distinct, anticorrelated resting state networks and lead to divergent networkconnectivity patterns. A combination of anterior and posterior brain network connectivity scores was found to be able to separatebvFTD from AD patients with a 100% accuracy. These results suggest that DT MRI and fMRI may improve the diagnosticdifferentiation of FTD from AD. Currently, however, none of these techniques taken in isolation has yet been proven to be “the”diagnostic tool for FTD, whereas a “multiparametric” approach, based on a combination of different MR techniques carryinginformation on the various aspects of the complex pathological picture of these conditions, is likely to be the most useful strategyfor an accurate diagnosis and to select an appropriate treatment algorithm.

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Federica Agosta, Massimo FilippiNeuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Scientific Institute and University “Vita-Salute” San Raffaele, Milan, Italy

L3 - Clinical heterogeneity

The chapter dealing with the group of degenerative non-Alzheimer dementias included in the “frontotemporal” spectrum hasundergone a deep revision in the last decade. Many of the clinical presentations included under this label were once considered asrare forms of degenerative dementia, typically associated with the pathological features of Pick’s disease. In contrast, frontotemporaldementia (FTD) is now conceived as a spectrum of clinical syndromes, reflecting a variety of pathological conditions.Neuropathologically, a basic distinction is now made between tau-positive and tau-negative pathology in FTD. A clinical classificationmust take into account recent advances in the phenotypic characterization of this clinical spectrum. A basic distinction to be madeis between behavioural and language presentations, a difference that tends to blur only with advanced disease progression. In bothcases, new diagnostic criteria, that take in adequate consideration the advances in the field of cognitive neuroscience, are in thecourse of development. In the case of behavioural presentations, the definition of the clinical phenotype needs to make reference toseveral concepts, which have been intensively investigated in the last few years in the social neuroscience literature, such assympathy, empathy and decision making. These central aspects of human behaviour need to be assessed with quantitativemeasures and adequately validated scales. In the case of language presentations, an excessive reliance on descriptive tools andmeasures derived from the vascular aphasia literature has now been superseded by the careful consideration of the crucial aspectsof language performance, which are affected, respectively, by the nonfluent/agrammatic, semantic and phonological/logopenicvarieties. In addition, appropriate consideration should be given to the complex motor manifestations that are frequently observed,in particular in patients falling within the diagnostic category of progressive aphasia affected by corticobasal degeneration orprogressive supranuclear palsy. Also in the latter case, the application of apraxia tests developed for patients affected bycerebrovascular lesions may not be ideally suitable to assess disease-specific motor features.

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Stefano F. CappaDepartment of Neuroclinical Sciences, Vita Salute University and San Raffaele Scientific Institute,Milan, Italy

Our future health depends on today’s medical experts minds, therefore, the SeronoSymposia International Foundation (SSIF), in partnership with the European NeurologicalSociety (ENS), has decided to establish a prestigious award to recognize and rewardexcellence in medical education.

The Serono Symposia International Foundation (SSIF) is seeking candidates amongmedical experts who are continuing to drive medical education forward through theirresearch and dedication in the field of neurology.

The criteria for candidate application cover a wide range of skills and attributes that SSIFis looking for in a potential candidate and winner of the SSIF award.

The Award Committee composed of Members of the SSIF Scientific Committee and Boardof Directors Members and ENS Members will assess the candidate’s professionaldedication and leadership to continuining medical education.

If you are a physician and/or scientist from 35 to 50 years old working in:• degenerative dementias and/or• multiple sclerosis and/or• neurodegenerative disease entailing movement disorders and/or• Parkinson’s disease

The SSIF Award will be a great opportunity for you!

Find out more and apply to the SSIF award on www.ssifaward.org

The winner of the SSIF award will receive Euro 10,000, less any taxes deductable, and will become a member of the SSIF advisory committee.

Applications are open for submission from May 28, 2011 until December 31, 2011.

SSIF awardRewarding scientific excellencein medical education

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