Cheol-Min Ghim earned his Ph.D. in theoretical physics from Seoul National University in 2003. After postdoctoral research at Center for Theoretical Physics, SNU (2003-2004), Center for Theoretical Biological Physics, University of California, San Diego (2004-2005), and Levich Institute of Physico-Chemical Hydrodynamics, New York (2005-2006), he had been working for Lawrence Livermore National Laboratory, US Department of Energy (2006-2009). He joined the faculty of UNIST in 2009 as an Assistant Professor of School of Nano-Bioscience & Chemical Engineering and Interdisciplinary School of Green Energy. He holds Visiting Scholar status in US DOE Lawrence Livermore National Laboratory since 2010.

Objectives: We report on a patient with dementia following herpes encephalitis who showed injury of a part of the Papez circuit (thalamocingulate tract between the anterior thalamic nuclei and the cingulate gyrus) on diffusion tensor tractography (DTT). Case report: A 45-year-old male had suffered from drowsy mentality, fever, and headache for three days. The patient was diagnosed as herpes encephalitis based on the clinical manifestations and the results of cerebrospinal fluid analysis, electroencephalography, and brain MRI. The patient’s symptoms almost disappeared by administration of acyclovir for two weeks. However, the results of neuropsychological testing at three months after onset indicated dementia. On the Mini-Mental Status examination, the patient scored 21/30. Results of the neuropsychological test performed at three months after onset showed verbal memory impairment on the Memory Assessment Scale (68 [2%ile]). In addition, the patient’s total score on the Memory Assessment Scale (84 [14%ile]) was relatively low compared with his total intelligence quotient on the Wechsler Adult Intelligence Scale (123 [94%ile]). Results: On three-month DTT, the neural tracts of the Papez circuit (fornix, cingulum, mamillothalamic tract, and thalamocingulate tract) were reconstructed in both cerebral hemispheres; however, the right thalamocingulate tract between the anterior thalamic nuclei and cingulate gyrus was disrupted. Conclusion: Our results indicate injury of the right thalamocingulate tract following viral encephalitis in this patient. We believe that the patient’s memory impairment was attributed, at least in part, to injury of the right thalamocingulate tract. Our results suggest the necessity of evaluation of the Papez circuit using DTT in patients with symptoms of dementia following encephalitis.

Jaqueline Botelho da Ponte interests include in neurology field, and the nutritional intervention with dementia diagnosis and treatment.

Patients with severe dementia, usually have problems the swallowing that leads them to have progressive weight loss . The aim of this study was to evaluate the profile of these nutritionally patients with severe dementia. Nutritionally n = 62 elderly patients were assessed ,all in CDR 3-attended the clinic Dementia UNIFESP / EPM , for the year 2013. The results indicate that 50 elderly were malnourished -Weight Md : 52.56 kg , height Md : 1,55 m , Body Mass Index - BMI Md : 21.21 kg/m2 , Arm Circumference - AC Md = 25 , 28 cm , triceps skinfold – TS Md = 11.39 mm , Circunfereência Muscular Arm - AMB Md = 21.70 cm Circumference and Calf - CC Md = 30.63 cm , valid for screening of nutritional diagnostic measures . Only 12 patients were normal weight - Weight Md = 52.58 kg , height = 1.55 m Md , Md BMI = 21.32 kg/m2 , PCT md = 11.53 cm , AC Md = 25.37 cm , AMB Md = 21.74 cm and CC Md= 30.64. Use beyond the anthropometric data , quality data supply, which indicates a diet low in calories and protein for all patients . Despite the modest sample be concluded that the findings corroborate the literature that emphasizes malnourished in severe stage of the disease , which leads us to invest in early nutrition.

Graduated in nutrition from the University Nove N utricionista the Team Nutrition Clinic of Neurology of the behavior UNIFESP / EPM N utricionista the Secular Health Clinic in Clinical Area

Patients with severe dementia, usually have problems the swallowing that leads them to have progressive weight loss . The aim of this study was to evaluate the profile of these nutritionally patients with severe dementia. Nutritionally n = 62 elderly patients were assessed ,all in CDR 3-attended the clinic Dementia UNIFESP / EPM , for the year 2013. The results indicate that 50 elderly were malnourished -Weight Md : 52.56 kg , height Md : 1,55 m , Body Mass Index - BMI Md : 21.21 kg/m2 , Arm Circumference - AC Md = 25 , 28 cm , triceps skinfold – TS Md = 11.39 mm , Circunfereência Muscular Arm - AMB Md = 21.70 cm Circumference and Calf - CC Md = 30.63 cm , valid for screening of nutritional diagnostic measures . Only 12 patients were normal weight - Weight Md = 52.58 kg , height = 1.55 m Md , Md BMI = 21.32 kg/m2 , PCT md = 11.53 cm , AC Md = 25.37 cm , AMB Md = 21.74 cm and CC Md= 30.64. Use beyond the anthropometric data , quality data supply, which indicates a diet low in calories and protein for all patients . Despite the modest sample be concluded that the findings corroborate the literature that emphasizes malnourished in severe stage of the disease , which leads us to invest in early nutrition.

Deborah C Oliveira graduated in 2009 with Bachelor and Teaching degrees in Nursing at the University of Campinas (Brazil). She then completed a MsC in Health Studies with anticipated support for care of community-dwelling older adults in a multicentre epidemiological study (FIBRA) in Brazil. She is currently in her second year’s PhD research at the University of Nottingham (United Kingdom) focused on the quality of life of older family carers of people with dementia. She has experience with research in quality of life, dementia, family carers, older adults and social support.

Patients with severe dementia, usually have problems the swallowing that leads them to have progressive weight loss . The aim of this study was to evaluate the profile of these nutritionally patients with severe dementia. Nutritionally n = 62 elderly patients were assessed ,all in CDR 3-attended the clinic Dementia UNIFESP / EPM , for the year 2013. The results indicate that 50 elderly were malnourished -Weight Md : 52.56 kg , height Md : 1,55 m , Body Mass Index - BMI Md : 21.21 kg/m2 , Arm Circumference - AC Md = 25 , 28 cm , triceps skinfold – TS Md = 11.39 mm , Circunfereência Muscular Arm - AMB Md = 21.70 cm Circumference and Calf - CC Md = 30.63 cm , valid for screening of nutritional diagnostic measures . Only 12 patients were normal weight - Weight Md = 52.58 kg , height = 1.55 m Md , Md BMI = 21.32 kg/m2 , PCT md = 11.53 cm , AC Md = 25.37 cm , AMB Md = 21.74 cm and CC Md= 30.64. Use beyond the anthropometric data , quality data supply, which indicates a diet low in calories and protein for all patients . Despite the modest sample be concluded that the findings corroborate the literature that emphasizes malnourished in severe stage of the disease , which leads us to invest in early nutrition.

Vivian Aparecida da Silva Salvador interests include in neuroscience, dementia, causes involved with dementia.

Patients with severe dementia, usually have problems the swallowing that leads them to have progressive weight loss . The aim of this study was to evaluate the profile of these nutritionally patients with severe dementia. Nutritionally n = 62 elderly patients were assessed ,all in CDR 3-attended the clinic Dementia UNIFESP / EPM , for the year 2013. The results indicate that 50 elderly were malnourished -Weight Md : 52.56 kg , height Md : 1,55 m , Body Mass Index - BMI Md : 21.21 kg/m2 , Arm Circumference - AC Md = 25 , 28 cm , triceps skinfold – TS Md = 11.39 mm , Circunfereência Muscular Arm - AMB Md = 21.70 cm Circumference and Calf - CC Md = 30.63 cm , valid for screening of nutritional diagnostic measures . Only 12 patients were normal weight - Weight Md = 52.58 kg , height = 1.55 m Md , Md BMI = 21.32 kg/m2 , PCT md = 11.53 cm , AC Md = 25.37 cm , AMB Md = 21.74 cm and CC Md= 30.64. Use beyond the anthropometric data , quality data supply, which indicates a diet low in calories and protein for all patients . Despite the modest sample be concluded that the findings corroborate the literature that emphasizes malnourished in severe stage of the disease , which leads us to invest in early nutrition.

Siddhartha Mondragon Rodriguez graduated in Chemical Engineering from Michoacan University of Saint Nicolas of Hidalgo (UMICH) in 1996 - 2002. Master Degree (MsC) in Molecular Biomedicine from National School of Medicine from the National Polytechnic Institute of Mexico City. PhD from Center of Research and Advanced Studies of the National Politechnical Institute in August 2005 - August 2009. PosdoctoralFellow from Universite de Montreal. Faculte de Medecine, Departament de physiologie., Montreal, Qc, Canada. Posdoctoral Position in McGill University

Alzheimer’s disease is defined by the presence of amyloid-β (Aβ) and tau protein aggregates. However, increasing data is suggesting that earlier phenomena such as brain network alterations rather that protein deposition could account for the pathogenesis of the disease. Here we found that earlier fragments of Aβ processing rather than plaque deposits are critically associated to abnormal function of brain networks. By measuring brain protein alterations in the hippocampus of Alzheimer’s J20 transgenic mouse model at four weeks of age, we found significant increases in β-CTF, a protein precursor to Aβ peptides. In addition, the β-CTF increase was found to be directly correlated with hippocampal circuit malfunction at this age. By performing extracellular field recording method at the subiculum region in vitro, we found reduced theta-gamma cross-frequency coupling at low (25-45 Hz) and high (150-250 Hz) gamma range. Interestingly, despite these network changes, the J20 mice did not present cognitive deficit at this age. In summary, our data suggests that brain network alterations precede the canonical Aβ protein deposition. In addition, we found that circuit alterations may be caused by β-CTF, suggesting that early pharmacological prevention of brain circuit alterations might represent a more promising strategy towards delaying the development of Alzheimer’s disease.

Jos Tournoy is head of the division of Gerontology and Geriatrics, University of Leuven, and vice-head at the Geriatrics Department and Memory Clinic of the Leuven University Hospitals, Belgium. He obtained his PhD (2006) on molecular mechanisms involved in Alzheimer’s disease. His clinical expertise includes age-related neurodegenerative diseases, including Alzheimer’s disease, in addition to general geriatric disorders. His research mainly focuses on determinants and markers of age-related cognitive decline and neurodegenerative disorders.

Background: In the phase III, pivotal trial, rivastigmine transdermal patch has shown higher caregiver satisfaction and greater preference than oral formulation in Alzheimer’s disease (AD) patients. We investigated not only caregiver preference but also treatment compliance of oral versus transdermal therapy for AD.
Methods: AXEPT was a 6-month, open-label, observational study in mild-to-moderately severe AD patients, from 32 centers in Belgium and Luxemburg. After treatment decision, patients were grouped into 2 cohorts: oral (donepezil, galantamine, rivastigmine, or memantine) versus transdermal (rivastigmine) therapy. The primary outcomes included caregiver preference (Questionnaire based evaluation, collected in transdermal treated cohort), caregiver satisfaction, and treatment compliance (Caregiver medication questionnaire scaled 0-10). Longitudinally, physician’s treatment preference (Questionnaire based evaluation) and adverse events (AEs) incidence were measured.
Results: Overall, 93 patients were enrolled between May-Nov 2010, of which 90 (mean age 79 years; 62% female; 64 [71.1%] in the patch cohort) were analyzed. The caregiver preference was 73% for the patch (most frequent reasons: easier to use, administer and comply) and 26.9% for the oral treatment. Treatment compliance was comparable between the cohorts (mean score: 9.15, patch; 9.71, oral). Average caregiver satisfaction score was 6.3 (patch); 7.4 (oral). Overall, 22 (71.0%) physicians expressed preference for a patch. No unexpected treatment related adverse events were reported.
Conclusion: Caregivers’ and physicians’ preference for transdermal therapy in AD were high and consistent with the literature. Compliance rates were similar between the cohorts and safety data reflect the known profiles of the different treatment formulations.

Paola Gagni is an Italian student graduated in 2011 in Pharmaceutical Biotechnology and now she is attending her PhD courses in Medicinal Chemistry at the University of Milan. She works on label and label-free protein microarrays at the Institute of Chemistry of Molecular Recognition (ICRM) of the CNR. She collaborates in a laboratory which uses Si/SiO2 supports, coated with appropriate polymers in order to increase binding capability and specificity of capture biomolecules.

Alzheimer Disease (AD) is characterized by abnormal extra cellular accumulation of β-Amyloid peptide in the brains of patients. The pathological isoform Aβ1-42 (Aβ42) agregates magnitudes of order faster than Aβ40 or Aβ39. However the analysis of the only Aβ42 concentration is not enough specific for the discrimination of AD from other kinds of Dementia in subjects with constitutionally high or low levels of total Aβ peptides. Thus, it may be better to consider the ratio between Aβ42/Aβ40 for higher reliability. In this way a method to detect simultaneously both analytes in cerebrospinal fluids is needed. Because of their multiplexing capability, the low volume sample consumption and the efficient sample-to-result time for population-wide screening, microarrays are ideal tools for the identification of individuals with preclinical AD who are still cognitively healthy. In this work, a highly sensitive immunoassay based on a label/label-free microarray platform that utilizes silicon/silicon oxide (Si/SiO2) substrates for the detection of the AD biomarkers Aβ40 and Aβ42 in artificial cerebrospinal fluid (ACSF) has been developed. In preliminary tests, the commercial peptides Aβ42 and Aβ39 aggregation status were assessed by Circular Dicroism, demonstrating the stability of Aβ42 structure for at least 2 hours, while Aβ39 does not show any conformational changes, even at 24 hours. Thereafter, an optimal antibody matched pair for Aβ42 detection was selected with a label and label-free microarray platform, using the Interfermometric Reflectance Imaging Sensor (IRIS), to determine binding yield on the silicon surface and the spot morphology. The selected antibodies were tested on copoly(DMA–NAS–MAPS) coated silicon chips for Cy3-label microarray analysis. Two antibody matched pairs resulted specific and sensitive for Aβ42. As these capture antibodies were against the peptide C-terminus, a different capture antibody was selected as specific for Aβ40. Both of the two peptides were simultaneously detected on a multiplexed fluorescence microarray using the same biotinilated antibody against the peptides N-termini and the respective LODs were extrapolated. The best condition developed for Aβ42 detection in ACSF requires 2 hours of dynamic incubation, resulting in a LOD of 73 pg/mL . In the same conditions the LOD for Aβ40 was 350 pg/mL. The obtained results are compatible for the use of the proposed assay in diagnostics, where CSF controls show a concentration of about 800 pg/mL for Aβ42 and 7 ng/mL for Aβ40. Moreover, our tool has been applied to detect these biomarkers in real human CSF samples, distinguishing between halthy and AD patients on the base of Aβ40/Aβ42 ratio. However, in contrast to the use of standard Aβ42 in ACSF, either static or dynamic overnight incubation resulted in an increased signal to noise ratio. This is most likely because in real human samples, the aggregation phenomenon observed in artificial CSF rarely occurs, and a longer incubation time allows the analyte to reach the equilibrium.

Deborah Cristina de Oliveira graduated in 2009 with Bachelor and Teaching degrees in Nursing at the University of Campinas (Brazil). She then completed an MSc in Health Studies with anticipated support for care of community-dwelling older adults in a multicentre epidemiological study (FIBRA) in Brazil. She is currently in her second year’s PhD research at the University of Nottingham (United Kingdom) focused on the quality of life of older family carers of people with dementia. She has experience with research in quality of life, dementia, family carers, older adults and social support.

Background:Perceptions and needs regarding quality of life (QoL) vary between general young and older populations and different types of instruments for the QoL assessment containing particular dimensions are available to each specific age group. In caregiving context, the increasing number of older people involved with the care for dependent family members with dementia and the higher impact of this task in physical, mental, economic and social dimensions when compared to youngers are recognized in the literature. However, instruments have being created and applied to mixed age groups of caregivers, regardless the specific needs in and perceptions of QoL in the older group. Objectives: A unique instrument aimed to assess the QoL of older family caregivers of patients with dementia is being developed, from the adaptation and validation process of the Huntington Disease Quality of Life Battery for Caregivers (HDQoL-C) to English older family caregivers of people with dementia. Methods: This study will be settled in two sequential phases: qualitative and qualitative, respectively. Focus groups will be performed with the target population to systematically investigate their views and perspectives with regards to their QoL in the context of caregiving, to the relevance of items of the HDQoL-C to their reality and to the WHO QoL construct. The instrument will be adapted based on these findings and on the opinions of a panel of experts. After this, the new instrument will be validated for use with older family caregivers, through a pre-test and pilot study, assessing the psychometric properties of this new instrument: its validity, reliability, stability and reproducibility, through adequate statistical analysis, in order to provide a valid and reliable instrument. Discussion and future directions: The study is being designed and a systematic literature review was carried out. The next step is to submit the project to Ethical approvals and the first phase of this study is intended to be developed this year.This will bea unique and specific instrument that reflects the views and needs of QoL of family caregivers in old ages caring for dementia people at home. It will allow researchers and health and social professionals to quantify the experience of care in old age in order to implement and evaluate therapeutic interventions with these people.

Wong Siew-Ying is a 4th year PhD student from National University of Singapore and her study is supported by NUS research scholarship. Having a strong interest in neuroinflammation and its implications in neurodegenerative diseases, she focused her research on neuroinflammation therapeutics. She also attended ISN-APSN Neuroscience School in 2012 and 2013 to further broaden her knowledge. Currently, she has a being accepted.

β-arrestins are adaptor proteins that complexes with G protein-coupled receptors (GPCRs) upon agonist binding and phosphorylation of receptor by G protein-coupled receptor kinases (GRKs). This subsequently leads to endocytosis of GPCRs via clathrin-coated pit and termination of GPCR signaling. Other than GPCRs sequestration, its role in transducing signaling has also been described. Moreover, β-arrestins has recently been suggested to involve in inflammation regulation. Being highly expressed in central nervous system, it would likely play an important role in the brain. In our previous work on brain postmortem tissue, we found that β-arrestin 2 but not 1 was downregulated in Alzheimer’s patients. As neuroinflammation plays a major role in the pathology of Alzheimer’s disease, we generated SH-SY5Y neuroblastomas with β-arrestin 2 knockdown to investigate its role in mediating neuroinflammation. SH-SY5Y were stimulated with tumor necrosis factor-α (TNF-α) and mRNA level of TNF-α, IL-8, CXCL10, and CXCL12 were measured using real-time PCR. Results revealed that all cytokines levels measured were significantly higher in SH-SY5Y β-arrestin 2 knockdown compared to wild type and empty vector control, indicating anti-neuroinflammatory role of β-arrestin 2. More work need to be done to elucidate the role of β-arrestin in regulating neuro-inflammation.

Dae Yul Kim,M.D.,Ph.D.2002–2005 Kobe University High Resolution Laser Spectroscopy PhD Japan.Kobe-shi 1998–2000 Pusan National University Physical Chemistry.M.S. South Korea · Pusan 1991–1998 Daegu University Chemistry.B.S.Department of Rehabilitation Medicine, Asan Medical Center, University of Ulsan College of Medicine, Korea.2014– present Senior Researcher Ulsan National Institute of Science and Technology · Department of Chemistry · Center of Superfunctional Material.2013– Mar 2014 Researcher Pusan National University · Research Institute for Basic Sciences South Korea · Pusan. Mar 2013 Assistant Professor The University of Electro-Communications · Institute for Laser Science · Hitoki Yoneda Japan Development of high average output THz spectroscopy, Nonlinear optical phenomena of atom-molecular using EUV Free electron laser.

Objective: Language deficits occur early in the course of Alzheimer’s disease. Applied correctly, nonliteral language is a worthwhile diagnostic tool to evaluate language and abstract thinking in dementias. The present study examined the neural mechanism in processing proverbs, and the difference in activation region according to characteristics of proverbs, using functional magnetic resonance imaging (fMRI). Methods: Twenty healthy adults with age from twenty to thirty-five were enrolled. Ten proverbs each in four categories-familiar, unfamiliar, opaque (difficult to understand), transparent (easy to understand) - were selected. Ten literal sentences were included for comparison. The sentences were presented on a screen while the subject was lying inside the MRI. Each sentence was shown for 4800 ms, and 200 ms was given between sentences. Total of 40 proverbs and 10 literal sentences were presented pseudo-randomly, in one of 4 predesigned sequences. We contrasted the activation regions of literal with figurative sentences, transparent with opaque proverbs, and familiar with unfamiliar proverbs. Results: Proverbs recruited right anterior cingulate cortex in comparison with literal sentences (uncorrected p-value <0.01). Opaque proverbs showed higher activity in the right dorsolateral prefrontal cortex, compared to transparent proverbs (uncorrected p-value <0.01). Familiar proverbs recruited the left dorsolateral prefrontal cortex when contrasted to unfamiliar proverbs (uncorrected p-value <0.01). Conclusion: The right anterior cingulate cortex is involved in processing of figurative language. In proverbs difficult to understand, the right dorsolateral prefrontal cortex is more activated. The right hemisphere shows to have a significant role in understanding proverbs in normal adults. These data will give the basic information of figurative comprehension of Alzheimer’s dementia.

Carien Hartmans has completed her M.Sc. at the age of 29 years from Utrecht University. Postdoctoral studies were completed from RINO, Utrecht in 2013. She just started publishing and has thus far published 2 papers in reputed journals. She is working with elderly patients as a specialist in clinical neuropsychology for Altrecht, a Dutch institute for clinical and outpatient mental health care.

Objectives: Investigating whether cognitive functioning is associated with the perception of one’s sexuality in old age. Design: Cross-sectional analysis, using observation cycle 2005/2006 of the population- based prospective cohort of the Longitudinal Aging Study Amsterdam. Setting: municipal registries in three Dutch regions. Participants: 1,908 older adults (mean [standard deviation] age: 71 [8.87] years; 54% women). Measurements: Sexuality and intimacy were assessed using four questions. Four cognitive domains were assessed: general cognitive functioning (Mini-Mental State Examination), memory performance (Auditory Verbal Learning Test), processing speed (Coding Task) and fluid intelligence (Raven’s Coloured Progressive Matrices). Multinomial regression analysis was used, with sexuality as outcome. The interaction effect between gender and sexuality was also tested. Results: Lower fluid intelligence was associated with perceiving sexuality as unimportant; lower general cognitive functioning was associated with perceiving sexuality as unimportant; and lower immediate memory recall was associated with evaluating sexual life as unpleasant. Associations were also found between lower fluid intelligence, processing speed, and general cognitive functioning, and agreeing with sexuality no longer being important. Lower processing speed, general cognitive functioning, and delayed memory recall were associated with disagreeing with a remaining need for intimacy when getting older. Finally, the association between fluid intelligence and perceiving sexuality as important, and the association between immediate memory recall score and evaluating sexual life as pleasant, was only significant in women. The association between lower general cognitive functioning and perceiving sexuality as unimportant seemed stronger in women compared with men. Conclusions: Higher cognitive functioning was associated with the way in which older people perceive their current sexuality.

DanjelaNdoja is a 35 years old neurologist epileptologist working at the University Public Hospital Center "Mother Theresa" in Tirana ALbania since 2011 graduated in Neurology in the University of Tirana Albania, and finishing the master of " Epileptology" at the University of Ferrara Italy 2012. My field of much interest beside her extensive work as general neurologist dealing at emergency with stroke or acute seizures cases, is caring the epileptic and dementia outpatients. Planning to attend soon in the future some other master on degenerative diseases.

Objective To evaluate the relationship of epilepsy and seizures in dementia. Materials; 17 patients among 42 recently dementia dealing patients, aged from 51 to 84 years old (median 67,7) who presented epileptic seizures following their cognitive decline were analyzed . Results; In 40,47% among dement patients epileptic seizures occurred approximately seven years following ongoing dementia of a median 16 points on MMSE, which was unapplied in 24% of them whose had SE or mute cases . Female incidence slightly prevailed comparing to male (53%; 47%), while the inverse occurred regarding the city residence which dominate in whom coming from capital then from other cities. Their previous history revealed; HTA 65%, stroke and surgery 23% respectively , DM 18%, brain coincidental tumors 12% , smokers, alcoholic drinkers, primary headache, primary epilepsy in a MR patient before dementia appearance of equal happening with 6%. All had negative familiar history of seizures. Dementia begun initially with memory decline 41%, gait disorders or misbalance 24%, parkinsonism 6%, epilepsy in MR 6%, the remained 33% had no clear cut designation of signs onset between the precedents. Concerning seizures semeiology; GTCS 47%, PMS 24%, nocturnal GTCS 17%, CPS 12%. Dealing diagnosis were; 24% VaD, HPN, MCI, AlzheimerD of 17% respectively, while FTD, MSA, cerebral palsy, or alcoholic pseudo dementia equally attributed with 6%. EEG findings; bilateral anterior theta rhythm and bilateral anterior IEDs 24% respectively , BiPLEDS prevailed in left F, anterior unilateral ShW and BA slow diffuse equally reported with 12%, FIRDA, left PLEDS and lateralized slow asymmetry of BA plus IEDs of same 6% occurrence , while 6% were unexamined . Imaging evidenced; post-stroke and sub cortical atrophy 24%, T cortical lobe prevailing atrophy , atrophy with ventricular dilatation and sub atrophy of 17% respectively , diffuse cerebral and cerebellar atrophy 15%, hydrocephaly with atrophy 12%. Treatment AEDs; VPA 37% , GBP 25%, CBZ 19%, PHT 13%, in one case with alcoholic pseudo dementia who presented the first seizure no AEDs was proposed. Conclusions HTA was the most associated issue with epilepsy-dementia. GTCS prevailed with 64% among brand of seizures. The lead diagnosis in patients with epilepsy following dementia was that of vascular origin similarly affirmed at imaging as well. The mostly reported epileptiform findings had bilateral anterior preponderance with 48%, while the most used AEDs drug controlling seizures was VPA.

Deborah Cristina de Oliveira graduated in 2009 with Bachelor and Teaching degrees in Nursing at the University of Campinas (Brazil). She then completed an MSc in Health Studies with anticipated support for care of community-dwelling older adults in a multicentre epidemiological study (FIBRA) in Brazil. She is currently in her second year’s PhD research at the University of Nottingham (United Kingdom) focused on the quality of life of older family carers of people with dementia. She has experience with research in quality of life, dementia, family carers, older adults and social support.

Objectives: To investigate factors associated with the anticipated support for care of 671 community-dwelling older adults in the city of Campinas, Sao Paulo, Brazil. Methods: This study utilized the data from the cross-sectional multicentre research network called "Frailty in Brazilian Older Adults" (FIBRA) (2008-2009). Anticipated support for care was assessed with a dichotomise question (yes or no): “If you need help to develop your activities of daily living, can you think in some one that would help you?”. If yes, it was asked how many people the older person believed that were available. Other variables of interest were: levels of frailty, self-rated health, sociodemographic conditions, levels of dependence and self-reported number of diseases. Descriptive and correlational (chi-square or F-test) analysis, as well as univariate and multivariate logistical regression were performed (IC 95%, p=0.05). Results: Female gender had worst socio-demographic conditions, poor perception of health, higher levels of dependence, more diseases, and lack of anticipated support for care. If they had someone to help them, in most of the cases just one person was referred. Advanced age was significantly associated with living alone and higher dependence for instrumental activities of daily living. The majority reported ‘good or very good’ health, irrespective of their age, although women were the majority in the group of ‘bad or very bad’ perception. In the univariate regression, female gender (OR: 2.06; 0.020), who lived alone (OR: 3.07; <0.001) and who had poor self-rated health (OR: 3.21; 0.004) showed greater risk for lack anticipated support for care. In multivariate levels, living alone (OR: 3.36; <0.001) and poor self-rated health (OR: 3.74; 0.002) continued significant, even when controlling by gender and age. Levels of frailty were not significantly associated with any variable studied. Conclusion: Brazilian older people in risk for lack of anticipated support are women, living alone and with poor self-rated health. It is necessary that health and social professionals identify those people in the community and provide them the necessary support or interventions. Also, it is necessary to reflect upon the formal support available to these people that do not have a family member to help them.

Ping li currentkly she is working as a professor at Sichuan center for disease control and prevention.Ping Li pursued her B.S from the Sichuan University, Chengdu, china in 1978-1982.She started her career as a Research assistant at The institute of pneumoconiosis of Chongqi, China during the years 1982-1985 and from 1985-1992 she worked as a Research associate at Health and Anti-Epidemic Center of Sichuan Province, Chengdu,china. Then she joined ibid as a associate professor in the year 1992 and she got promoted to professor in 2001.

Objective To investigate the relationship of depression degree in aged population and selenium content to APOE gene polymorphism in deferent selenium level areas. Methods Choose two rural areas, appropriate selenium level (Qionglai) and low selenium level (Jiange); Selecte 500 volunteers over 65 by cluster sampling method, to carry out the Geriatric Depression Scale (GDS).and relevant cognitive questionnaire respectively. Nails and finger blood are sampled simultaneously to detect the selenium level and APOE gene, 50 volunteers are required to sample vein blood for detecting blood selenium level. Evaluate the depression degree by continuous GDS score (scores between 11 and 20 are generally considered to represent significant mild depression and scores of 21 or higher are considered severe depression). Difference between different areas on distribution of depression degree, nail’s selenium content and APOE gene polymorphism is tested by t test and chi-square test. Results Results from two areas show good correlations between blood selenium and nail selenium level. Significant statistical differences are observed between two areas both in nail selenium level（P＜0.001） and distribution of APOE gene polymorphism（P＜0.0001）. Difference of constituent ratio of depression degree is significant too, in which the number of depression patients in Jiange is more than that in Qionglai. Divide all 1000 subjects into two groups according to the nail selenium content (group 1 with nail selenium content <0.259μg/g and group 2 >0.259μg/g). The frequency of geneε2/2、ε2/4、ε3/4 in group 1 is lower than group 2, with significant difference（P＜0.05）. The ratio of alleleε2、ε3、ε4 in group 2 is higher than group 1, with statistical difference. Ratios for Alleleε2、ε3、ε4 of APOE are significant different either in different areas or different nail selenium content groups. As for the distribution of gene polymorphism comparison, all five genotypes have statistical difference in different area groups, but only three of them (ε2/2, ε2/4, ε3/4) have statistical difference in nail selenium content groups. Conclusions Population’s selenium levels are different in different selenium level areas. There is correlation between selenium level and APOE gene polymorphism, geneε2/2 only appears in population with higher selenium content. Patients of depression in lower selenium area are more than that in area with higher selenium level, which shows the possibility of selenium being risk factor for aged depression. Key words-- rural elderly population; Selenium; APOE; Geriatric depression

Kaitlyn P. Roland completed her Ph.D. at the University of British Columbia in 2012 (Canadian Institutes for Health Research and Parkinson Society Canada funded). Her Ph.D. work helped understand Parkinson-related changes to daily muscle activity (electromyography) and consequences for physical function and frailty, especially in females. She is currently completing postdoctoral studies at the University of Victoria’s Centre on Aging (Canadian Institutes for Health Research and Michael Smith Foundation for Health Research funded). Her most recent work has focused on categorizing the physical, cognitive and neuropsychiatric symptoms that influence care needs and well-being in dementia caregivers across disease groups (i.e., Alzheimer’s disease, Dementia with Lewy Bodies and especially Parkinson’s disease related Dementia). Overall, her research program aims to support independent living, and reduce distress and healthcare utilization, which may have significant public health implications.

Dementia caregiving can incur both negative (such as burden) and positive (such as higher self-esteem) reactions. Burden is a predictor of caregiver morbidity and mortality, while self-esteem reduces anxiety and promotes well-being. The comparative impact of caring for varying behavioural problems, cognitive impairments, declines in daily living abilities (ADL) and of care-recipient depression on caregiver reaction is unclear. This study asked: does the care-recipient’sbehaviour, cognition, ADL, or mood contribute most to caregiver burden and self-esteem? Caregivers were recruited through referral as part of a larger provincial research program in B.C., Canada. Caregivers provided 3+hours of care over 3 days/week and care-recipients were on cholinesterase therapy for 6-months. 906 caregivers (n=613 spouses) were interviewed in-person and cared for persons with Alzheimer’s (58.9%), vascular (11.6%), lewy body (5.4%), Parkinson’s (1.2%) and other/mixed dementia (22.9%). 81% of care-recipientswere community-dwelling. Stepwise multiple regression models revealedgreater ADL dependence andcare-recipient depression(P<0.005, R2=0.10) predicted burden.Only care-recipientdepression directly predicted self-esteem (P=0.013, R2=0.02).Providing care for ADL and care-recipient moodcontribute to burden; however, managing care-recipients’ mood had the greatest impact on caregivers’positive reactions. Care-recipient mood significantly influences caregiver reactions; recent frailty literature suggests this may result from the inability to manage depression and/or find meaning in new caring-relationship roles. While reactions to caregiving are diverse, healthcare providers should aim to increase satisfaction of caring and provide clinical and community support for managing depression in care-recipients. Findings highlight the clinical importance of mood symptoms to both patient outcomes and caregiverwell-being.

research. Knowing that neuroinflammation is implicated in the pathology of many neurodegenerative diseases, she started looking for potential therapeutics for neuroinflammation diseases and molecules mediating neuroinflammation. As limited therapeutics is available for neurodegenerative diseases, she hope with her research work and contributions, she could soon find therapeutics that could ameliorate disease conditions and improve living quality of patients.

Substantial evidence gained over the past two decades has supported the conclusion that neuroinflammation is associated with Alzheimer’s disease (AD) pathology. Therefore, keeping neuroinflammatory responses regulated with anti-inflammatory compounds could be beneficial in ameliorating the disease conditions. In our study, we investigated andrographolide, a bioactive molecule isolated from Andrographis paniculata with anticancer and anti-inflammatory activities. Recent work suggested that andrographolide can inhibit the inflammatory actions of microglia, but its effects on chemokine production and other molecular markers of reactive astrogliosis are unclear. Using rat primary astrocytes, we showed that andrographolide treatment attenuated release of chemokine CCL5 andupregulation of glial fibrillary basic protein (GFAP) after IL-1β stimulation. Moreover, treatment of andrographolide before and after LPS stimulation inhibited the elevation of CCL5, CXCL5, CXCL1, CXCL10, CX3CL1, and CCL2 chemokines mRNAs, suggesting potential effects of andrographolide in attenuating leukocytes recruitment into the brain during neuroinflammation events. Andrographolide also decreased activation of c-Jun N-terminal kinase (JNK) and nuclear factor-κB p65(NF-κB), the key regulator of inflammation. These results suggested andrographolide being a potential anti-neuroinflammation compound and it should be further assessed for its efficacy in conditions characterized by significant neuroinflammation, including AD.

Li Yong currentkly she is working as Technologist-in-charge, assistant of Ping Li at Sichuan center for disease control and prevention. Li Yong received her B.S from the Sichuan University, Chengdu, china in 1998-2003 and M.S in nutrition and food hygiene from Sichuan University, Chengdu, China. She started her career in 2006-2007 as a Visiting scholar of Western light, National institute of occupational health and poison control, Beijing, China and from 2007-present she working as a Technologist-in-charge, assistant of Ping Li，Sichuan Center for Disease Control and Prevention, Chengdu, China.her Research field is The relationship between trace elements and human health.

The AD cause weight loss by the metabolism state these patients or by inadequate intake of dietary calories. The aim of this study was to determine whether protein-energy supplementation improves or maintains the nutritional status of these patients. Study followed for 6 months, 12 patients with CDR 1 and 2, and 6 men and 6 women with MMSE of Md=18.9 and Md=5 years of schooling. All received 2 daily doses of dietary supplement (600 kcal, 24.0 g/ptn) and weight, height, triceps skinfold (TS), arm circumference (AC) and arm muscle circumference (AMC) were evaluated. The results indicates: Height Md=1.59 m and gain of 1.2 kg after 6 months (57.03-58.3), resulting in increased BMI. The AC had a mean gain of 0.85 cm (25.67-26.52), AMB + 0.69 cm (21.56-22.25). TS remained unchanged, indicating that the gain was muscle mass. Although the results obtained is modest, it indicates that the addition of the oral supplement is required to maintain or improve the nutritional status of these patients and consequently the quality of the food.

Mitchell K.P.Lai received his BSc from the University of Alberta, Canada in 1995 and her PhD from the Department of Pharmacology, University of Sydney, Australia in 2003. From 2003-2009, he was Principal Research Scientist with the Dept. of Clinical Research, Singapore General Hospital. She first joined the National University of Singapore (NUS) as a Research Fellow in 2010, then Research Assistant Professor in 2011 under the Memory, Aging and Cognition Centre. In 2012,she joined NUS Dept. Pharmacology as an Assistant Professor. Her research interests include neurochemistry of dementia, “Omics” and molecular mechanisms of neurodegeneration.

Introduction: Neuro inflammation is an important feature of Alzheimer’s disease (AD). However, little is known about the inflammatory status of dementia with Lewy body (DLB), which has both AD (plaque and tangle) and alpha-synuclein pathologies. Methods: Levels of β-amyloid (Aβ1-42), phosphorylated tau (pS396 tau) as well as inflammatory cytokines interleukin-10 (IL-10), IL-12, IL-13 and interferon γ (IFN-γ) in neocortical brain homogenates from aged controls, AD and DLB cases were measured using ELISA and Luminex assays. Results: AD and DLB both showed significant Aβ1-42 and p396 tau burden, at levels significantly higher than controls. In contrast, only AD showed significantly higher levels of inflammatory markers, while neuroinflammatory markers are not raised in DLB. Discussion: Despite similar burden of AD pathology, DLB has a relatively mild neuro inflammatory response compared with AD. The efficacy of anti-inflammatory therapeutic approaches may therefore be more limited in DLB.

Dr Pierre A. Denis has received an M.D. degree in 2004 in the Université de Nantes (France) during the period of 1994-2004 . He is currently working as an emergency physician in the French town of Saint-Malo. As a general practitioner, his research goals are to get a better understanding of the etiology of diseases such as cardiovascular diseases, cancer and neurodegenerative diseases. He has authored 3 research articles.

Angeles Martin Requero is Doctor of Biological Sciences, Complutense University of Madrid in 1978. she completed Postdoctoral Fellow in University of Pennsylvania, Philadelphia, USA in 1979-1982. She worked as as a Professor in University of Extremadura (1982-1983). Scientific Holder in 1985. In 1996-1997 she worked as a Visiting Scientist in Medical Scholl, University of California (UCLA), Los Angeles, USA. In 2008 she is a Research Scientist.she currently heads the laboratory devoted to “study the cellular and molecular basis of Alzheimer’s disease and other dementias, ” in the Department of Cellular and Molecular Medicine, Center for Biological Research (CSIC). She has authored more than 50 publications in international journals and a hundred communications in national and international conferences.

Null mutations in GRN are associated with Frontotemporal Lobar degeneration with TDP-43 inclusions (FTLD-TDP). However the influence of progranulin (PGRN) deficiency on neurodegenation is largely unknown. In neuroblastoma cells, silencing of GRN gene causes significantly reduced cell survival after serum withdrawal. We observed that PGRN deficient cells (KD GRN) are more vulnerable to serum deprivation than control cells. The supplementation of recombinant human PGRN restored the survival of KD cells. The following observations suggest that modulation of the CDK6/pRb pathway secondary to changes in the activity of the PI3K/Akt and ERK1/2 signaling pathways, induced by PGRN levels is involved in the altered regulation of serum deprivation-induced apoptosis. (i) The specific CDK6 inhibitors, sodium butyrate or PD332991 sensitized control SH-S5Y5 cells to serum deprivation-induced apoptosis without affecting survival of PGRN deficient cells. (ii) CDK6/pRb seems to be downstream of the PI3K/Akt and ERK1/2 pathways since their specific inhibitor, Ly294002 and PD98059 were able to decrease CDK6 activity and induced death of control SH-SY5Y cells. (iii) PGRN deficient cells show reduced stimulation of Akt, ERK1/2, and CDK6-associated kinase activities than in control cells in the absence of serum. These observations highlight the important role of PGRN-mediated stimulation of the PI3K/Akt/ERK1/2 and CDK6/pRb pathways in determining the cell fate survival/death under serum deprivation.

Null mutations in GRN are associated with Frontotemporal Lobar degeneration with TDP-43 inclusions (FTLD-TDP). However the influence of progranulin (PGRN) deficiency on neurodegenation is largely unknown. In neuroblastoma cells, silencing of GRN gene causes significantly reduced cell survival after serum withdrawal. We observed that PGRN deficient cells (KD GRN) are more vulnerable to serum deprivation than control cells. The supplementation of recombinant human PGRN restored the survival of KD cells. The following observations suggest that modulation of the CDK6/pRb pathway secondary to changes in the activity of the PI3K/Akt and ERK1/2 signaling pathways, induced by PGRN levels is involved in the altered regulation of serum deprivation-induced apoptosis. (i) The specific CDK6 inhibitors, sodium butyrate or PD332991 sensitized control SH-S5Y5 cells to serum deprivation-induced apoptosis without affecting survival of PGRN deficient cells. (ii) CDK6/pRb seems to be downstream of the PI3K/Akt and ERK1/2 pathways since their specific inhibitor, Ly294002 and PD98059 were able to decrease CDK6 activity and induced death of control SH-SY5Y cells. (iii) PGRN deficient cells show reduced stimulation of Akt, ERK1/2, and CDK6-associated kinase activities than in control cells in the absence of serum. These observations highlight the important role of PGRN-mediated stimulation of the PI3K/Akt/ERK1/2 and CDK6/pRb pathways in determining the cell fate survival/death under serum deprivation.

Garcia Osta A received her Bachelor Degree and her PhD in Pharmacy from the University of Navarra, Spain. Her postdoctoral training was obtained in the Alberini’s laboratory, in the Neuroscience Department at the Mount Sinai School of Medicine in New York. She joined the Neuroscience Department of CIMA in 2007. She is Investigator in the laboratory of Neurobiology of Alzheimer’s disease and she interested in the investigation of molecular basis of dementia in Alzheimer Disease. As an independent group, she leads several projects related to the search for new therapeutic targets to reverse the dementia associated with the pathology of Alzheimer’s disease.

Null mutations in GRN are associated with Frontotemporal Lobar degeneration with TDP-43 inclusions (FTLD-TDP). However the influence of progranulin (PGRN) deficiency on neurodegenation is largely unknown. In neuroblastoma cells, silencing of GRN gene causes significantly reduced cell survival after serum withdrawal. We observed that PGRN deficient cells (KD GRN) are more vulnerable to serum deprivation than control cells. The supplementation of recombinant human PGRN restored the survival of KD cells. The following observations suggest that modulation of the CDK6/pRb pathway secondary to changes in the activity of the PI3K/Akt and ERK1/2 signaling pathways, induced by PGRN levels is involved in the altered regulation of serum deprivation-induced apoptosis. (i) The specific CDK6 inhibitors, sodium butyrate or PD332991 sensitized control SH-S5Y5 cells to serum deprivation-induced apoptosis without affecting survival of PGRN deficient cells. (ii) CDK6/pRb seems to be downstream of the PI3K/Akt and ERK1/2 pathways since their specific inhibitor, Ly294002 and PD98059 were able to decrease CDK6 activity and induced death of control SH-SY5Y cells. (iii) PGRN deficient cells show reduced stimulation of Akt, ERK1/2, and CDK6-associated kinase activities than in control cells in the absence of serum. These observations highlight the important role of PGRN-mediated stimulation of the PI3K/Akt/ERK1/2 and CDK6/pRb pathways in determining the cell fate survival/death under serum deprivation.

Farías GA, Pérez P, Slachevsky A, Maccioni RB. 2012. “Platelet Tau Pattern Correlates with Cognitive Status in Alzheimer's Disease.” Journal of Alzheimer's disease : JAD 31(1): 65-69. - Guzmán-Martínez L, Farías GA, and Maccioni RB. 2012. “Emerging Noninvasive Biomarkers for Early Detection of Alzheimer's Disease.” Archives of medical research 43(8): 663-666. -Devic I, Hwang H, Edgar JS et al. 2011. “Salivary α-synuclein and DJ-1: potential biomarkers for Parkinson's disease.” Brain : a journal of neurology

Neurodegenerative diseases such as Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) are currently considered as protein misfolding diseases. Determination of pathogenic proteins -mostly in Cerebrospinal fluid (CSF) samples- has been proposed as a disease biological marker that can be used for diagnosis and follow up. Furthermore there are some reports that describe protein “profiles” in CSF from carriers of neurodegenerative diseases. Due to difficulties in CSF sampling, it would be very useful to count with reliable biomarkers in peripheral fluids. Levels of peripheral Amyloid Beta (AB), AB precursor protein (APP) and tau -among others- have been evaluated for AD diagnosis, while alpha-synuclein and DJ1 have been used as PD biomarkers. Previously we have evaluated peripheral blood platelets tau as a reliable AD biomarker. We performed measures and characterization of pathogenic proteins in blood and saliva obtained from neurodegenerative disease carriers (PD, AD and other protein misfolding diseases) by immunoblot and ELISA analyses. We describe the specific peripheral protein profile that characterizes different neurodegenerative diseases. We also describe the relation between clinical disease features -measured with standardized clinical scales like UPDRS and MMSE- and levels of pathogenic proteins in blood and saliva and finally we discuss the relevance and implications of our analyses for diagnosis and further physiopathologycal knowledge of these diseases.

Objectives: Driver performance in different road conditions with and without the use of distraction offers valuable information concerning driving safety, yet it is difficult to investigate during on-road driving. Herein, we present initial findings on speed of driving of MCI and mild AD patients and middle aged/older healthy controls in two Rural driving simulation environments: High Traffic with and without distraction (conversation). Moreover, total number of crashes in unexpected incidents, were computed separately for all Rural and Urban driving conditions of the experiment. The study aims to examine the contributions of traffic load and distraction to measures of driving behavior in the above groups. It is part of a larger driving simulator experiment funded by the National Strategic Reference Framework (NSRF 2007-13, O.P. “Thales”), which integrates subject variables with driving conditions. Methods: Participants: In these analyses, 52 drivers were included: 22 controls (mean age: 56.4 ±8.9), 22 mild cognitive impairment (MCI) patients (mean age: 66.41 ±10.00), and 8 mild AD patients (mean age: 73.13 ±8.81), Number of participants entering each type of analysis varied. Measures: Average speed (in km) in each condition and during each unexpected incident specifically. Two unexpected incidents occurred per condition. Total number of crashes for all Rural and Urban environments (4 conditions per environment: High and Low Traffic, with and without distraction). Results: Univariate analyses of variance were performed for each of the measures, with group as fixed variable and age as covariate, comparing each patient group to the control group. Both age and participant type were significant (p ≤ .01) in the Rural High Traffic without distraction condition. AD patients drove more slowly than controls in the High Traffic without distraction environment (p ≤ .05). Only age was significant (p ≤ .05) in the Rural High Traffic with distraction condition. Univariate analyses of variance of the unexpected incident situations showed that AD patients were marginally slower than the control group in one of the two incidents with distraction. Nonparametric (Kruskal-Wallis) tests showed that the distribution of total number of crashes did not differ in the Rural condition but was significantly different in the Urban Condition only, with controls showing fewer crashes (p ≤ .05). The low number of participants who have completed the more challenging Urban condition thus far precluded comparisons of speed across the four groups. Conclusion: AD patients drove slower than controls in Rural High Traffic without distraction and were marginally slower during the unexpected event with distraction. Age was also an important determinant of speed. The lower speed of AD patients appears to relate to cognitive decline. The Urban environment is more demanding for the patients’ ability to handle unexpected incidents. Findings will be corroborated with the addition of more patients. Preliminary associations of performance with neuropsychological variables will be presented.

Zdena Kristofikova has graduated from Czech Technical University in Prague (Department of Nuclear Chemistry) and has completed his Ph.D. from the Faculty of Military Healh Science, University of Defence in Hradec Kralove, Czech Republic (Department of Toxicology). She works at Prague Psychiatric Centre as a neurochemist and is interested in Alzheimer disease for a long time. She has published 50 papers in reputed journals.

It is suggested that multifunctional mitochondrial enzyme 17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10) can interact with amyloid β via high-affinity binding and that free as well as bound enzyme probably plays a role in the pathogenesis of Alzheimer disease (AD). Our previous experiments revealed that 17β-HSD10 levels in cerebrospinal fluid are a relatively high sensitive but less specific biomarker of AD (significant changes in 17β-HSD10 were observed already in people with mild cognitive impairment due to AD, a comparison of AD patients with non-demented controls revealed a sensitivity of 80.0% and a specificity 73.3%; however, a specificity was only 52.5 – 59.1% when compared to various types of dementia; moreover, enzyme overexpression was also found in people with schizophrenia or multiple sclerosis). Levels of complexes of enzyme and amyloid β in cerebrospinal fluid were not the better biomarker of AD that those of total enzyme with respect to the high-sensitivity of complexes to neuroinflammation. It seems that enzyme overexpression could reflect dysfunctional mitochondria. On the other hand, correlation analysis indicated the significant shifts from negative correlations in controls to positive correlations in AD people between 17β-HSD10 levels and age or between those and Mini Mental State Examination score. We think that 17β-HSD10 overexpression observed in AD could play the neuroprotective rather than toxic role and that the treatment of AD by means of potent, highly specific inhibitors of enzyme should not be very successful. Supported by GACR P303-11-1904 project.

García-Osta received her B. degree and her Ph.D. in Pharmacy from the University of Navarra, Spain. Her postdoctoral training was obtained in the Dr. Alberini´s laboratory, in the Neuroscience Dpto at the Mount Sinai School of Medicine in New York. Dr. García-Osta joined the Neuroscience Department of CIMA in 2007. She is Investigator in the laboratory of Neurobiology of Alzheimer´s disease and she interested in the investigation of molecular basis of dementia in Alzheimer Disease. As an independent group, she leads several projects related to the search for new therapeutic targets to reverse the dementia associated with the pathology of Alzheimer's disease. At present, lines of work are related to molecules that inhibit the acetylation of histones (iHDACs), drugs phosphodiesterase 5 inhibitors and growth factors using gene therapy to access different brain areas. The scientific and production group has led to two patent applications in Alzheimer's disease as well as numerous publications in high impact scientific journals.

Therapeutic approaches based on agents that regulate signalling pathways involved in processes of memory formation could be good options to treat cognitive decline that occurs not only in different pathological conditions such as Alzheimer´s disease (AD), but also in normal aging. Phosphodiesterases (PDE) are enzymes that catalyze the hydrolysis of adenosine and/or guanosine 3′, 5′ cyclic monophosphate (cAMP or cGMP). cAMP/cGMP regulate signalling cascades that lead to the phosphorylation and activation of the transcription factors cAMP responsive element binding protein (CREB), one of the most important molecules in neuronal plasticity processes including learning and memory. PDE5 inhibitors have been shown to effectively restore memory function in animals in both physiological and different pathological conditions. Among them, Tadalafil, by its longer half-life and its safety profile could be a reliable good option for enhancing cognition. In the present study, the effect of tadalafil on PDE5 by measuring cGMP levels in the CSF of non-human primates was primarily analysed. Furthermore, the effect of a chronic treatment with tadalafil on cognitive function and on hippocampal spine density was studied in aged-mice. Two hours after tadalafil administration, cGMP levels in CSF of non-human primates were significant higher than the basal levels. A chronic treatment of 5 weeks with tadalafil produced a cognitive enhacement effect in both the Morris water maze and the fear conditioning test. This effect was accompanied by an increase in spine density of apical dendrites of CA1 pyramidal neurons and with a significant increase in the hippocampal brain derived neurotrophic factor (BDNF).

Apostolos Hatzitolios is Professor of Internal Medicine and Head of First Propedeutic Department of Internal Medicine, AHEPA Hospital, Medical School, Aristotle University of Thessaloniki. He is President of Internal Medicine Society of Northern Greece and he has 131 publications in PubMed.

Background/Aim: Atherosclerosis is commonly implied after the findings of carotid ultrasound and lower limp Doppler studies and has also been associated with dementia. Recent studies have shown that patients with vascular dementia (VD) exhibit a cholinergic deficit and they have a good response to treatment with acetylocholinesterase inhibitors (AchI). There is evidence in thyroid mouse models in in vitro studies that achetylocholine stimulates iodine organification without concomitant T4 release. The aim of this study was to assess thyroid function after AchI treatment in VD patients and to investigate its therapeutic impact in patients with VD and impaired atherosclerotic markers. Methods: 68 patients who were admitted with diagnosis of stroke and VD were included. As controls there were 50 healthy individuals. The patient group completed a 12 months therapy with AchI (rivastigmine), while the control group received placebo. Cognition was evaluated by the Mini-Mental State Examination (MMSE) and serum thyreotropine (TSH), Free T4(FT4) and FreeT3(FT3) were measured once before the initiation of therapy and at the end of 3rd, 6th and 12th month of treatment. We investigated changes in thyroid parameters before and after the administration of AchI. Atherosclerotic markers included imaging by duplex of carotid and femoral arteries, has been done before the beginning of AchI treatment and at the completion of the study after 12 months, in order to detect the presence of atherosclerotic plaque and to assess the intima-media thickness (IMT),as a calculated marker of subclinical atherosclerosis and subsequently a potential VD. Each artery was assigned a score (presence of plaque=1, absence of plaque=0, IMT > 0.8mm=1, IMT<0.8mm=0) and the total score of the 4 vessels (2 carotid and 2 common femoral) was calculated per each patient (atherosclerotic ultrasonic score - ATHUS). Subsequently, the MMSE of every patient was reevaluated. Brain CT scans were performed to exclude other reasons for the intellectual decline of patients. Results: 12 months after treatment MMSE score was unchanged in 45/50 control individuals and improved in 60/68 patients(p<0.001). It seems that AchI benefit patients with VD at least 12 months but not controls. Patients group (ATHUS=3-6, 55 patients) was associated with median MMSE of 27. The corresponding value of the control group (ATHUS=0-2, 40 persons) was 30 (p<0.05) Conclusion: Our results suggest that AchI treatment has the potential to offer clinical benefit after 12 months of treatment to VD patients who also have evidence of atherosclerotic vascular disease.

Melinda Martin-Khan PhD MHthSc GCSc(Stat) BEd(Hons) BCom(Acc) DipMan is a Research Fellow at the Centre for Research in Geriatric Medicine at The University of Queensland School of Medicine, Australia.

Introduction The diagnosis of dementia is likely to be a protracted process – sometimes unnecessarily so. Delays, from the point of initial recognition of a cognitive issue, are often the result of either: not recognising the signs of early cognitive decline; a limited understanding of the benefits of timely diagnosis; or delayed access to the next step in the diagnostic process. While research is ongoing, there is evidence to support the usefulness of a timely diagnosis of dementia. Aim This project is specifically interested in local and international examples of service models which focus on reducing the time lag to diagnosis. Method A review of the international literature, including grey literature, was conducted. Contact was made with service providers identified as carrying out relevant activities, even if associated health service research had not already been completed for these activities. A scoping study in the State of Queensland, Australia was carried out to identify interactions between general practice clinics and memory clinics and what responses have been taken at a practical, and unpublished, level to improve access. Results Computerised databases were searched, resulting in 188 records after removal of duplicates. Following a formal systematic process, 21 papers were included in the final review. Four key strategies were identified for improving access to specialist assessment of dementia: increasing the number of clinics across a wider geographic area; a mobile team where one specialist visits an individual in their home and completes the assessment; single point of referral for all patients in one region – patient sent to the closest memory clinic or one with a shorter waiting list; specialists consult at the local general practitioner’s clinic (GP). 53 general practitioners were surveyed across the 11 State Medicare local districts. A representative from each of the 15 memory clinics in Queensland was also interviewed. In some instances, doctors were unaware of the State health care policy and had not experienced any impact since it’s introduction. Those doctors in more remote areas reported evidence of improved access to diagnostic support following the introduction of the policy. Significance Early/timely diagnosis of dementia is often overlooked as an opportunity for change, given the challenges associated with prevention, treatment and/or cure. This project summarises approaches taken around the world for improving access to timely diagnosis of dementia.

Heledd H Griffiths has been researching into the cell biology of Alzheimer’s disease for 9 years with Professor Nigel Hooper. She gained her PhD from the University of Leeds at the age of 27, in 2009. As a post-doctoral researcher, she has been awarded two 3-year funded grants from Alzheimer’s Research, UK. Work from her first grant was published in the Journal of Biological Chemistry and awarded ‘Best paper in neurobiology 2013’. She has recently moved over to the University of Manchester alongside Professor Nigel Hooper to continue her research. She has published 9 papers and currently has 3 under review.

The cellular prion protein (PrPC) is a high-affinity neuronal receptor for amyloid- (A) oligomers, mediating neuronal impairment via the activation of Fyn kinase and phosphorylation of tau1, 2. The -secretase, ADAM10, which cleaves the amyloid precursor protein (APP) releasing the neuroprotective sAPP and precluding the formation of A, also sheds PrPC from the cell surface3, 4. We hypothesised that modulation of the shedding of PrPC by ADAM10 would alter the binding and neurotoxicity of A oligomers. SH-SY5Y cells were treated with siRNA targeted against ADAM10 or with pharmacological agents (e.g. carbachol, resveratrol) to reduce or activate ADAM10 activity, respectively. siRNA knockdown of ADAM10 resulted in increased full length PrPC at the cell surface and increased the amount of A oligomers bound to the cells. Antibody blocking of the Aβ oligomer binding site on PrPC prevented the increase in binding observed following ADAM10 siRNA. Conversely, up-regulation of ADAM10 activity promoted the shedding of PrPC from the cell surface, and consequently reduced the binding of A oligomers to cells. The specificity of each activator for ADAM10 was tested by monitoring sAPPα production following siRNA knockdown of ADAM10. Carbachol modulates ADAM10 activity, but also modulates sAPPα production via a different pathway, whereas resveratrol solely modulates sAPPα production via ADAM10. Developing specific agonists of ADAM10 will not only preclude A formation and up-regulate neuroprotective sAPPα, but it will also prevent the binding of soluble A oligomers to PrPC and prevent the aberrant activation of signaling pathways which lead to neurotoxicity.

Márcia Regina Cominetti is an PhD in Physiology, from Federal University of São Carlos in 2004 and received a FAPESP fellowship to pursue a doctoral research stage at University of Virginia Health System, Charlottesville, VA, USA in 2002. I went to a post-doctoral stage at INSERM, in Paris, France from 2005 to 2006. I currently work at UFSCar as an Associate Professor and my research interests are Cellular Biology and Biochemistry, mainly in the following topics: Alzheimer's disease and cancer.

Dementia from Alzheimer’s disease (AD) is the most common type of dementia, accounting for approximately 60% of the cases. Regarding the immense financial, physical and emotional burden of AD, there is a pursuit to find sensitive and specific biomarkers for this disease. Since the brain histological hallmarks of the disease are amyloid-β1-42 (Aβ1-42), total Tau (T-Tau) and Tau phosphorylated (P-Tau), these molecules have been extensively studied. Aβ peptide is proteolytic fragment of APP released by sequential cleavages via β and γ-secretases. In healthy subjects the predominant route of APP processing consists of successive cleavages by α and γ-secretase. ADAM10 is the most important α-secretase involved in cleavage of APP. Previous studies have demonstrated that protein levels of platelet ADAM10 are reduced in AD patients. In this context, the aim of this study was to verify the total blood and platelet ADAM10 gene expression in elderly patients with AD dementia and to compare with mild cognitive impartment (MCI) and healthy elderly subjects. Blood from AD patients, MCI and normal controls was collected and analyzed by RT-qPCR techniques, using standardized primers for ADAM10 and to endogenous controls. One-way analysis of variance followed by Bonferroni as a post hoc comparison and Mann-Whitney U followed by multiple comparison (Kruskal-Wallis and Dunn's Multiple Comparison Tests) tests were performed. It was observed no differences between total blood and platelets ADAM10 gene expression in AD patients compared with MCI or controls patients. Samples for total blood were divided according to CDR and the results were similar, with no difference in ADAM10 gene expression between patients (CDR1, CDR2 or CDR3) and controls (CDR0). In this way, the decrease of ADAM10 protein levels in platelets from AD patients is not caused by a reduction in platelets or total blood ADAM10 mRNA levels. Further studies must be performed in order to investigate the influence of other molecules in this pathway, as micro RNAs, for instance. This would contribute to understand the pathophysiological mechanisms of AD.

Katherine Kellett received her PhD from King’s College London in 2005 and has since worked in the laboratory of Professor Nigel Hooper, researching into Alzheimer’s disease and mammalian proteases for the last 9 years. In this time she has worked on two grants funded by Alzheimer’s Research UK and has published 12 papers. Along with the rest of Professor Nigel Hooper’s research group, Kate recently moved her work to the University of Manchester.

The accumulation of amyloid β-peptide (Aβ) into insoluble plaques in the brain is a key event in the pathogenesis of Alzheimer’s Disease. The first step in Aβ formation is the cleavage of the amyloid precursor protein (APP) by the β-site APP cleaving enzyme (BACE1). The processing of APP by BACE1 can be regulated by a number of different proteins; in this study we sought to identify proteins that modulate BACE1 cleavage of APP using an siRNA screening approach.An siRNA screen was performed using a protease sub-library to knockdown the expression of a range of different proteases (430 targets) in human embryonic kidney 293 cells expressing an N-terminal alkaline phosphatase tagged APP695 construct (APAPP) and overexpressing BACE1. APP and BACE1 siRNA knockdown were tested as positive controls and a WST-1 cell proliferation assay was used to check cell number. Following siRNA knockdown APP processing was monitored by analysis of conditioned media for alkaline phosphatase activity to measure soluble AP-APP fragments. 25 proteins were identified to significantly affect APP cleavage in the initial screen: 22 positive regulators (decreased APP cleavage) and 3 negative regulators (increased APP cleavage) of APP processing were identified. Of the 22 positive regulators, 5 were selected as potential hit candidates (Neurolysin, Bone Morphogenic Protein 1 (BMP-1), Lipoprotein A (Lpa), Kalikrein-related peptidase 6 (KLK6) and Matrix Metallopeptidase 7 (MMP7)) and were further tested for their effects on APP processing by analysis of sAPPβ levels by western blot. Neurolysin, BMP-1, Lpa and MMP7 were shown to not specifically affect BACE processing of APP as determined by analysingsAPPβ; KLK6, however,significantly decreasedsAPPβ. The effect of siRNA knockdown of KLK6 on APP processing was further investigated by analyzing sAPPα, sAPPβ and Aβ using the Mesoscale Discovery System. KLK6 knockdown significantly decreased sAPPβ and also decreased Aβ38, Aβ40 and Aβ42, although not significantly. In addition KLK6 knockdown also decreased sAPPα. These changes were not due to a change in total APP levels, as determined by western blot. These data indicated that KLK6 may affect APP processing and the effect of KLK6 on APP processing warrants further investigation. In addition, we have validated an siRNA screening approach for identifying novel regulators of APP processing.