Chair

Claude M Wischik

TauRx Therapeutics, UK

Co-Chair

Zhicheng Xiao

Monash University, Australia

Session Introduction

Teresa Juarez-Cedill

National Medical CenterCentury, Mexico

Title: Effects of diabetes and depression on cognitive function in patients with Dementia: (Sadem study)

Biography:

Teresa Juárez Cedillo from Aging Area Mexican Social Security Institute, Mexico. She is currently in Epidemiological Research Unit.

Abstract:

Objective: We examine the patterns of cognitive functioning in individuals diagnosed with dementia, diabetes, and depression as compared with dementia plus diabetes, or dementia plus depression and healthy controls. Methods: 207 participants with dementia, 83 with Alzheimer’s disease, 66 vascular dementia and 58 mixed dementia were included. All subjects underwent global neuropsychological assessment via the Mini-Mental State Examination, and assessment for depressive symptoms via the Center for Epidemiologic Studies Depression Scale. Diabetes diagnoses were confi rmed by the medical examination Results:A mixed-eff ects repeated measures analysis of covariance indicated a signifi cant diff erence in cognitive functioning between the study groups. Our results showed that patients with diagnosis of dementia and depression showed greater cognitive dysfunction compared to controls, but to a lesser degree in patients with comorbid dementia diabetes. Conclusions: Th ese results suggest that dementia, when combined with depression or diabetes mellitus, adversely aff ects cognitive performance.

Claude M Wischik

TauRx Therapeutics, UK

Title: The place of tau in the pathology, treatment and prevention of Alzheimer’s disease and frontotemporal dementia

Biography:

Claude M Wischik holds the Chair in Old Age Psychiatry at the University of Aberdeen in Scotland, and is Executive Chairman of TauRx Pharmaceuticals. He studied medicine in Australia, completed his PhD at the Laboratory of Molecular Biology in Cambridge, and also higher psychiatric training in Cambridge. He was the fi rst to identify Tau protein as the main constituent of the Alzheimer tangle and developed the fi rst Tau Aggregation Inhibitors. He has published 121 papers and holds 11 patent groups based on his work with over 40 individual patents.

Abstract:

In Alzheimer’s disease (AD), the microtubule associated protein Tau, is implicated in a self-amplifying aggregation cascade which kills nerve cells and transmits the pathology to otherwise healthy neurons, spreading the disease throughout the brain in manner that is quantitatively linked to the degree of clinical dementia. A similar process occurs for Synuclein in PD. Th e Tau Aggregation Inhbitors (TAIs) we have developed block this process in cell models and reduce Tau pathology in transgenic mouse models. Th e fi rst of these (methylthioninium, MT) to be tested in a large Phase 2 clinical trial in AD reduced the rate of disease progression by 90% over 12 months on clinical and imaging endpoints. Th e brain concentration required for clinical effi cacy is the same as that required for TAI activity in model systems. Phase 3 trials in mild and moderate AD are currently underway globally (including Canada) aiming to confi rm the Phase 2 results, using an improved version of the drug (LMTX®). We are also conducting a Phase 3 trial in FTD, where either Tau or TDP-43 proteins aggregate, both blocked by LMTX®. Th e initial results will be available in the fi rst half of 2016. If the Phase 3 trials are successful, LMTX® could be used preventatively, since Tau aggregation aff ects about 50% of the over-45 population, but progresses slowly at the early stages. LMTX® also reduces pathology in a Synuclein mouse model of PD, so we aim to conduct trials with LMTX® in PD in the future.

Zhicheng Xiao

Monash University, Australia

Title: APP intracellular domain suppress neuronal differentiation through transcriptional regulation of mir663

Biography:

Zhi-cheng Xiao, PhD. received a Doctor of Natural Science degree from Swiss Federal Institute of Technology, Zurich. He is current Professor in Monash University. He is the CEO& CFO of iNovaFarm, a premier Bio-Tech company. He has published more than 100 papers in reputed journals and serving as editorial board members of more than 10 journals.

Abstract:

Amyloid precursor protein (APP) is best known for its involvement in the pathogenesis of Alzheimer’s disease. We have previously demonstrated that APP intracellular domain (AICD) regulates neurogenesis; however, the mechanisms underlying AICD-mediated regulation of neuronal diff erentiation are not yet fully characterized. Using genome-wide chromatin immune precipitation approaches, we found that AICD is specifi cally recruited to the regulatory regions of several microRNA genes, and acts as a transcriptional regulator for miR-663, miR-3648 and miR-3687 in human neural stem cells. Functional assays show that AICD negatively modulates neuronal diff erentiation through miR-663, a primate-specifi c microRNA. Microarray data further demonstrate that miR-663 suppresses the expression of multiple genes implicated in neurogenesis, including FBXL18 and CDK6. Our results indicate that AICD has a novel role in suppression of neuronal diff erentiation via transcriptional regulation of miR-663 in human neural stem cells.

Ornit Chiba-Falek

Duke University Medical Center, Durham, USA

Title: The functional role of an Alzheimer’s disease associated poly-T variant in TOMM40 gene

Biography:

Ornit Chiba-Falek is an Associate Professor at the Department of Neurology at Duke University. Her lab has been studying the genetic factors and molecular mechanisms underlying neurodegenerative diseases in aging with a focus on the functional consequences of non-coding variants in dementia and Lewy bodyrelated disorders. She has received her PhD from the Hebrew University in Jerusalem before pursuing her postdoctoral training at the NIH; she was a recipient of the Ellison Medical Foundation New Scholar Program in Aging Award in 2008. She is an Academic Editor for PLoS ONE and serves on the Editorial Boards of JPAand AIMS-Genetics.

Abstract:

We investigated the TOMM40-APOE genomic region that has been associated with the risk and age of onset of lateonset Alzheimer’s disease (LOAD) and with cognitive function in healthy aging to determine if a highly polymorphic, intronicpoly-T within this region (rs10524523, hereaft er 523) aff ects expression of the APOE and TOMM40 genes. Alleles of this locus are classifi ed: Short-S, long-L, very long-VL based on the number of T-residues. We analyzed two brain regions from Caucasian donors,APOEε3/3 and APOEε3/4autopsy-confi rmed LOAD cases and APOEε3/3 normal controls. Diff erences in APOE-mRNA and TOMM40-mRNA levels were evaluated as a function of 523-genotype. Th e expression of both genes was signifi cantly increased with disease. Mean expression of APOE-and TOMM40-mRNA levels were higher in VL-homozygotes compared to S-homozygotes in temporal and occipital cortexes from Normal and LOAD carriers of APOEε3/3 haplotype. Similarly, among APOEε3/4 LOAD subjects APOE and TOMM40-mRNAs expression were increased in VL-heterozygotes compared to S-heterozygotes brains.We further investigated the eff ect of the 523 locus in its native genomic context using a luciferase reporter system.Th e results were consistent with the human brain mRNA analysis: Th e 523-VL resulted in signifi cantly higher expression than the S in both HepG2 hepatoma and SH-SY5Y neuroblastoma cell-lines. Collectively, these results suggested that the 523 locus may contribute to LOAD susceptibility by modulating the expression of TOMM40 and or APOE transcription.In conclusion, our study elucidated the mechanism of action of TOMM40-523, a genetic risk factor for LOAD and provides functional support for the role of the 523 locus in the pathogenesis of LOAD.

Asokan Chinnasamy

Sokoto State University, Nigeria

Title: Interaction of soluble and amyloid form of serum amyloid aprotein to BC3H1 cells

Biography:

Asokan Chinnasamy has completed his PhD at the age of 27 years from University of Madras and Postdoctoral studies from Columbia University, USA. He is the Associate Professor, Department of Biochemistry, Sokoto State University, Nigeria. He has published more than 36 papers in reputed journals and has been serving as an Editorial Board Member of reputed journals.

Abstract:

The BC3H1 smooth muscle cells of mice brain, the study was carried out membrane binding. Th is is important in relation to the activity of membrane proteins because losing the activity of such systems will ultimately lead to malfunction or death of the cell. Th e interactions of Serum Amyloid A (SAA) and Serum Amyloid A protofi brils with BC3H1 cells of the mouse are dealt with in detail to study the binding of SAA protofi brils in various conditions. Th e FACScan and MTT assay results have shown the SAA and SAA fi brils binding and cell toxicity with the BC3H1 cells with diff erent concentrations of Serum amyloid P component and Amyloid enhancing factor. Specifi cally, cells were incubated with 1.25-6.25 μM SAA-FITC and SAA protofi brils-FITC assayed. Th e 50% viable BC3H1 cells at 4-6 μM with an LD50 of 3.5 μM. Th e interaction of serum amyloid A fi brils with a cell surface binding site/receptor might alter the local environment to cause cellular dysfunction and to be more favorable for amyloid formation. Th e RAGE (receptor for advanced glycation endproducts) a polyvalent receptor in the immunoglobulin super family has been implicated in binding with the isoform of SAA (SAA1.1) which has the highest fi birillogenic property. Th e present study concludes the SAA fi brils more binding and cell cytotoxicity than SAA protein.

Break: Lunch Break: 13:30-14:20 @ Foyer

Chair

Barbara Fisher

United Psychological Services, USA

Co-Chair

Eef Hogervorst

Loughborough University, UK

Session Introduction

Magda Stroinska

McMaster University, Canada

Title: Keep the conversations going! Gricean maxims in the Old age

Biography:

Magda Stroinska is Professor of German and Linguistics at McMaster University in Hamilton On, Canada. Her major areas of research include sociolinguistics and cross-cultural pragmatics, in particular cultural stereotyping, language and politics, propaganda, the issues of identity in exile, aging and bilingualism. More recent areas of interest and research focus on language and psychological trauma. She co-edited a number of books, most recently Unspeakable: Narratives of trauma (with Vikki Cecchetto and Kate Szymanski, Peter Lang 2014).

Abstract:

This paper continues our research on communication with the elderly and off ers some suggestions for those who work in geriatric care. With the demographic challenges resulting from the changing population age patterns, we believe that this interface of pragmatics and gerontology is of special signifi cance. It may seem common sense that in a normal, everyday conversation speakers expect their interlocutors to follow the co-operative principle. Some linguists dismiss the need for Gricean maxims as we generally assume that people will do “the right thing” at the right time unless we have a good reason to believe otherwise. But what would be a good reason? We know that culture may be at odds with some of the maxims. Can age also be a factor that infl uences the degree to which speakers adhere to Gricean maxims of conversation? And if so, can the maxims still be defended as relevant for the interpretation of what people have to say? Many people have had the experience of talking to an elderly parent, relative or friend and realizing with frustration that they did not seem to “co-operate”. Repeating the same stories, telling signifi cantly more than asked for, digressing (i.e. violating the maxim of relevance), or simply telling things that we know cannot be true are just some of the things that may happen in conversations with the elderly interlocutors, giving rise to the multitude of stereotypical representations of the aged in popular fi lms or in literature. Th ough partly fi ctional and oft en exaggerated, these representations refl ect popular (mis)perception of seniors. Using dialogs from a number of main stream English language fi lms depicting elderly people suff ering from dementia of Alzheimer’s disease, we analyzed to what extent the subjects appear to meet the expectation of obeying the Gricean maxims and how the other (non-senior) participants react to the violations. Th e results show that most caregivers or relatives react with diff erent levels of frustrations and oft en try to constantly correct or even ridicule the senior, oft en resulting in the senior person withdrawing from the conversation. Knowing that they are NOT doing “the right thing,” we tend to insist that they realize their mistakes and reason the way we do. Th is, of course, is in most cases impossible. However, seniors with mild dementia or suff ering from Alzheimer disease oft en make sense according to the reality they are living in and their statements may be consistent with each other within that modifi ed setting. It is not impossible to adapt to that reality and keep the conversation going without necessarily compromising the maxims ourselves. If someone says that their deceased spouse brought them fl owers that morning, a reply that would not frustrate the senior could be “I see you miss him” or “he always did that, didn’t he?” or even “what fl owers did he bring you?” As language not only serves the purpose of communication with others but is also is the necessary instrument of thought, it may be more important to simply keep the conversation going than to ascertain who is right. With the aging of the baby boom generation we are facing a dramatic increase in the number of seniors and people suff ering from dementia in the years to come. Anything that can help seniors to retain a grip on reality is of utmost importance and keeping the communication alive may serve this purpose. However, it is also necessarily to help caregivers by giving them tools for communicating with patients without frustration. Th is research is suggesting very simple and easy to follow guidelines for such tasks.

Catherine Braxton

Generations Senior Care Consulting, USA

Title: Improv and technology skills training for youth and adolescents resulting in more effective and meaningful communication among the young caregiver and Dementia sufferer

Time : 15:50-16:20

Biography:

Catherine Braxton has working in the field of Alzheimer’s and related dementias for almost 20 years. She received her BA from the University of Illinois and completed all Master level course work at National Louis University. Catherine has worked with patients and families in a consultative, supportive and educational capacity in health care facilities, where she started the first support groups at multiple senior facilities. Catherine creates tailored educational techniques that will empower the entire family and presents her sensitivity training to health care facilities including local hospitals. Catherine was a guest speaker at the Alzheimer’s Association Family Forum in the spring of 2014.

Abstract:

Caring for a person suffering from a form of dementia affects the entire family and requires an entire family to make it work. Adolescents and children are aware of their family dynamic whether the dementia sufferer lives with them or is demanding more attention from their parents outside of the home. The focus of this specialized training is to enhance effective communication and create meaningful moments with the dementia sufferer. Donaldson et al, 1998 identified the most effective caregiver style as supporters... who adapt to the patients level of functioning... creating a safe environment and minimizing frustration for the patient. In-home sensitivity training, empathy enhancement, effective communication strategies and reminiscing skills can empower this population to become supporters within the caregiving environment. They can become an integral role in the caretaking process. Enlightened behavior, namely empathy can replace the guilt of a caregiver (Burns, p 81). Caregivers who learn about the disease can then learn to empathize with the patients, providing an enhanced quality of life. This awareness coupled with the research that indicates that interactions between caregiver and patients impact patient behavior (Teri, 1999) clearly demonstrate that the young population require special attention in order to positively enhance interactions. A personally tailored, fun approach to in-home sensitivity training as well as skill training on effective communication techniques, empathy enhancement exposure and reminiscing through technology will empower this young generation to feel adequate to interact with a dementia sufferer and effectively provide meaningful moments.

Ana Patricia Aguilera Hermida

Penn State University, USA

Title: Brain Power, a Course for Older Adults

Biography:

Ana Patricia Aguilera Hermida is a Doctoral student and lecturer at Penn State University. She is a Psychologist with a Master in Family Therapy. She has been teaching since 1995, from elementary school through the master’s level. Because of her passion in education, she created a school for older adults in Mexico. Another accomplishment is the creation of curricula for the Master Integral of Family Therapy to UVM, a school part of Laureate International Universities. She is very interested in neuroplasticity.

Abstract:

As part of the process of aging, some older adults experience diminishment of cognitive abilities. The decline may become sufficiently serious that older people are not able to live independently or manage their lives. It has recently been shown that cognitive training can promote neural and cognitive plasticity (Draganski et al., 2006). Slowing decline of the aging mind is both an economic and quality of life issue that impacts the emotional well-being of older adults and their families or caregivers (Greenwood & Parasuraman, 2010; Goh & Park, 2009). I developed a course for preventing cognitive decline as a primary prevention strategy. When courses are focused on specific cognitive functions, such as memory or visuospatial ability, participants found them irrelevant and not related to their lives (Fang et al., 2009). Therefore, the structure of this course is holistic. Cognitive decline has a multifactorial etiology, resulting from interactions between both genetic and environmental factors (e.g. gene APOE, diabetes, vascular insults, neuronal damage, and high cholesterol/triglycerides), so the interventions have to be conducted multidimensionally, combining interventions for multiple risk factors (Srisuwan, 2013). Following a multidimensional and holistic structure, the course will have six basic components: education, meditation, cognitive stimulation through senses, emotions, social impact, and physical activity. I am presenting the structure of the course and the possible benefits for older adults.

Tangui Maurice

University of Montpellier, France

Title: Development of sigma 1 receptor agonists as neuroprotectants in Alzheimers disease and related dementia

Biography:

After graduating chemical engineer from ENSCM (Montpellier, France) in 1987, Tangui Maurice got his PhD in neuropharmacology in 1990. He made 2 post-doctoral fellowships at the Jouveinal research institute (Paris) and Nagoya University Hospital and Meijo University (Nagoya, Japan). He joined CNRS in 1992 starting to work on sigma-1 receptors . He is now team leader at INSERM U. 710 (U. 1198 since 01/01, 2015). He gots 120+ publications and 4 patents. Tangui Maurice also created a CRO company, Amylgen, co-founded with 3 scientists from university and industry, where he is currently acting as CSO.

Abstract:

The sigma-1 receptor (S1R) is a ligand-operated molecular chaperone localized on endoplasmic reticulum (ER), mitochondria and plasma membranes. Its activation modulates IP3 receptor-dependent Ca2+ mobilizations, facilitates the activation of ER stress sensor proteins and kinase pathways. Under chronic activation, it also recomposes lipid domains in membranes, which are highly functionalized domains. Interestingly, the chaperone can be directly activated (or inactivated) by several classes of ligands. These S1R agonists are potent neuromodulatory and neuroprotective drugs in different neurodegenerative insults and pathologies (stroke, Alzheimer's disease (AD), Parkinson's disease, ALS…). We examine the involement of the S1R in AD pathology and validate selective or non-selective S1R agonists as neuroprotective agents. First, we analyzed the impact of S1R invalidation (using S1R KO mice) on the vulnerability to AD pathology. Two main AD models were used, a nontransgenic model by direct icv injection of oligomeric amyloid- (A) protein fragments [25-35] (A25-35) in mice and transgenic lines overexpressing hAPPSwe or hAPPSweInd. We observed that AD toxicity and behavioral deficits are significantly amplified in S1R KO mice injected with A25-35 and in S1R KO x hAPPm lines. Second, we showed the protective potency of S1R agonists and mixed muscarinic/S1R ligands in AD models. The pathology was analyzed in terms of ER and oxidative stress, inflammation, mitochondrial damage, cell loss, memory deficits, increased APP processing and Tau hyperphosphorylation. We therefore confirmed the role of endogenous neuroprotection system in neurodegenerative processes and identified S1R agonists as potent neuroprotective and putatively disease-modifying agents.

Session Introduction

Kay Donnellon

University of Cumbria, UK

Title: Communication and comfort measures for people with Dementia at end of life: Integrating specialist services in community settings

Biography:

Kay Donnellon is a senior lecturer within the University of Cumbria in advanced clinical practice and palliative care in both undergraduate and post graduate programmes. After a long career in community and primary care, palliative care has remained a passion and has allowed her to develop collaborative working arrangements with local hospices assisting in accrediting modules with them. She is a current PhD student researching quality in out of hours services where she is an active member of her local clinical governance group as well as an Advanced Nurse Practitioner.

Abstract:

Because we are all growing older and living longer, the chances of many of us having to live and die with dementia are increasing. Care at end of life can be particularly challenging in this context. Th is study assesses the impact of a series of workshops for care home staff on improving communication and comfort measures at end of life for people with dementia. Interviews and observational visits were conducted three months later with carers to assess whether these approaches had been embedded into practice. Th e evidence that was gathered demonstrated that carers could make a signifi cant diff erence to a person’s comfort and care at the end of life, even within the context of dementia. Giving carers frameworks for pain assessment and exploring multiple communication methods, promoting confi dence in the approaches they were taking and empowering them not to “leave their emotions at the front door” – all these had enabled carers to provide eff ective and compassionate multidisciplinary palliative care for their residents with dementia. It had also enabled people with dementia to remain in their existing care homes as so many of them had originally requested.