Please consider the following presentations. Each presentation is embargoed per the information below.
Oral Presentations
Sunday, July 14, 2013
Session Title: Therapeutics: Preclinical Studies: APP, ABeta, and APOE
Session Number: O1-11
Presentation Number: O1-11-05
Pharmacological inhibition of the Aβ and Apolipoprotein E Interaction Ameliorates Alzheimer's Pathology in APPSW/PS1dE9 /apoE2-TR and APPSW/PS1dE9 /apoE4-TR Mice (Oral Presentation)
Authors -Martin J. Sadowski, Joanna E. Pankiewicz1, Jungsu Kim, Maitea Guridi, Sandrine
Sanchez, Michael C. Granovetter, Patrick M. Sullivan, David M. Holtzman,
Background: Disturbance of β-amyloid (Aβ) homeostasis and its accumulation in the brain underlie early Alzheimer's disease (AD) pathogenesis. Apolipoprotein (apo) E is a lipid carrier protein, which directly interacts with Aβ promoting its oligomerization, deposition in parenchymal plaques and in the brain vasculature, and also influences the rate of Aβ brain clearance. APOE alleles are well-recognized genetic risk factor for sporadic AD and correlate with severity of β-amyloidosis. APOE4 increases AD risk, while APOE2 shows a relative protective effect. Here, we investigate effects of the treatment with a pharmacological inhibitor of the apoE/Aβ binding on AD pathology in APPSW/PS1dE9 /apoE2-TR (TR=targeted replacement) and APPSW/PS1dE9 /apoE4-TR mice.
Presenter and co-chair of this session - Martin J. Sadowski, MD, PhD, associate professor, Departments of Neurology, Psychiatry, and Biochemistry & Molecular Pharmacology, NYU School of Medicine
Embargoed for Release until Sunday, July 14, 2013 4:00PM - 5:30PM
Tuesday, July 16, 2013
Research Session –Featured Research Session
Focus on Family: Cross-Setting Interventions to Promote the Effectiveness and Well-Being of Families Coping with Dementia
Chair(s): James E. Galvin, MD, MPH; Marie Boltz, PhD, RN, GNP-BC
Session Description: The growing incidence and impact of Alzheimer's disease will exert considerable strain upon health care delivery and demand interventions that support the effectiveness of informal support systems of the person with dementia (PWD). Family caregivers provide the majority of care to the PWD, playing a critical role in the detection of cognitive impairment, the maintenance of the safety, comfort, and function of the PWD, coordination of care, and medical decision-making. However, the toll of their efforts can be significant. Although caregivers report positive feelings about caregiving, the majority describe significant emotional stress and strain, placing them at risk for depression, acute illness, chronic disease, health care utilization and even death. Methods to improve the health care experience for both the person with dementia and their caregiver are warranted to improve clinical outcomes for the PWD, alleviate caregiver strain and stress, avoid unnecessary costs, and positively influence organizational cultures around dementia care. This session will provide a review of four studies, conducted in different types of settings (acute care, outpatient care, private homes, shared housing) that demonstrate the essential contribution of family caregivers to the PWD's health and quality of life.
Multicultural Family Detection of Dementia (Oral Presentation)
Background: It is estimated that 5.4 million Americans live with Alzheimer's Disease (AD), and over the next 20 years as the incidence, morbidity and mortality rates will increase dramatically. Much AD research has been done in Caucasian populations. However Hispanics are the fastest growing minority in the US and it is now estimated that over 275,000 Hispanic older adults have AD and 1.3 million are projected to be affected by 2050. Additionally, African American older adults may be at higher risk for AD than Caucasians and typically present at later stages. Little attention has been placed on the role of socio-demographic factors including age, gender, education, language, race, ethnicity, and cultural beliefs in the detection of AD and related dementias by patients, families and family caregivers of different backgrounds.
Objectives: Develop culturally- and linguistically-sensitive methods to improve detection of dementia in older adults and understand the impact of early detection on patients and their families.
Methods: We applied brief medical, interview and performance tasks to detect dementia and dementia risk factors (diabetes, hypertension, obesity, and frailty) in a multicultural sample of community-dwelling older adults; tested the acceptance of, preferences about, and compliance with dementia screening recommendations across cultures; and confirmed screening results with a Gold Standard clinical and cognitive assessment.
Conclusions: Detection of dementia at earlier stages is possible using culturally- and linguistically-sensitive methods. Older adults are very interested in their cognitive health. Acceptance and compliance with screening is improved if memory screening is placed in the context of promoting healthy brain aging than if posed as dementia detection.
Presenter: James E. Galvin, MD, MPH, professor, Departments of Population Health, Psychiatry and Neurology, Comprehensive Center on Brain Aging, NYU Langone Medical Center
Family-Centered Strategies to Promote Cognitive and Functional Recovery in Acutely Ill Persons with Dementia (Oral Presentation)
Background: Approximately one-quarter of all hospital patients aged 65 and older are people with Alzheimer's and other dementias. In addition to the physiological challenges experienced by older patients, these individuals are typically exposed to non-dementia friendly environments. Consequently, as compared to other older patients, persons with dementia (PWD) are more likely to experience complications including functional decline and delirium. They have longer hospital stays, and are more likely to be transferred to an institution for long-term stay. They also are more likely to be readmitted to the hospital within 30 days of discharge. In addition, when the person with dementia (PWD) is hospitalized, the stay for the caregiver is often associated with intense worry and stress, as well as increased burden during and after the hospital stay.
Objectives: Our objective was to test the feasibility and utility of FC-FFC (Family-centered Function-focused Care), a system-level intervention that actively engages families in the assessment, decision-making and evaluation of interventions to promote physical activity and cognitive stimulation in the person with dementia, during the hospital stay and immediate post-acute period.
Methods: Using a repeated measures design, we evaluated upon admission, discharge, 14 and 60 days post-discharge in hospitalized person with dementia and their caregivers : 1) patient outcomes (functional performance/capability, cognition, and recidivism; and 2) family carer outcomes (preparation for discharge, affect, strain, mutuality), as compared to the control units which received education only. Qualitative data supplemented these measures. Enrollment and treatment fidelity data (goal attainment, staff knowledge, and protocol adherence) were collected.
Results: The FC-FFC arm demonstrated improvements in the experiences and outcomes of both family carer and patients.
Conclusion: FC-FFC has the potential to improve outcomes for hospitalized older adults and family caregivers during and after the hospital stay.
Presenters: James E. Galvin, MD, MPH, professor, Departments of Population Health, Psychiatry and Neurology, Comprehensive Center on Brain Aging, NYU Langone Medical Center, Marie Boltz, PhD, RN, GNP-BC, assistant professor, NYU College of Nursing
Embargoed for Release until July 16 2013 8:30AM - 10:00AM ET
Tuesday, July 16, 2013
Reversal of Synaptic Plasticity and Spatial Memory Deficits in APP/PS1 Mice by Suppressing Protein Kinase GCN2 (Oral Presentation)
Authors: Tao Ma, MD, PhD, assistant research professor and Eric Klann, PhD, professor, NYU Center for Neural Science
Background: The amyloid beta (Aβ) hypothesis of Alzheimer's disease (AD) has resulted in current research focusing on lowering levels of brain Aβ, a small peptide derived from amyloid precursor protein. Meanwhile, the signaling pathways downstream of Aβ as well as Aβ-independent mechanisms are also being vigorously pursued as potential disease-modifying targets. One such potential target is the protein kinase GCN2, which is important in controlling mRNA translation via phosphorylation of eukaryotic initiation factor 2α subunit (eIF2α). Interestingly, elevated eIF2α phosphorylation has been correlated with AD pathogenesis, potentially via mechanisms of oxidative stress. Here taking advantage of a mutant mouse model in which eIF2 kinase GCN2 is deleted (GCN2 KO), we examined whether repression of eIF2α phosphorylation could alleviate synaptic and memory deficits associated with APP/PS1 AD model mice.
Conclusions: Our findings indicate that AD-associated impairments in synaptic plasticity and memory can be prevented by decreasing GCN2-dependent eIF2 phosphorylation, which might be linked to enhanced translation. These studies suggest that GCN2 and eIF2a are viable therapeutic targets for synaptic dysfunction in AD and other related dementia syndrome.
Presenter - Tao Ma, MD, PhD, assistant research scientist, New York University Center for Neural Science
Embargoed until Tuesday, July 16, 2:15PM – 3:45PM
Thursday, July 18, 2013
Session Title: Therapeutics: Preclinical Studies Novel Approaches II
Presentation Number: O5-06-01
Monoclonal Antibody Therapy Targeting the Shared Pathological Conformer of both Aβ and Hyperphosphorylated Tau (Oral Presentation)
Authors - Fernando Goni, Daniel Peyser, Krystal Herline, Yanjie Sun, Thomas Wisniewski
Background: Currently there is no effective therapy for Alzheimer's Disease (AD). Active and passive immunomodulation still holds promise but current attempts only address one side of the pathology: either amyloid β (Aβ) or the hyperphosphorylated tau (ptau) protein. Furthermore current approaches are not specific for the pathological conformers of either protein. From our novel immunization method targeting pathological β-sheet conformation we developed monoclonal antibodies, some of them with promising binding capacities; and we propose to characterize a monoclonal specific for pathological conformers of Aβ and tau (TAB1) to be used for immunotherapy in AD mouse models.
Conclusion We believe that immunotherapy that specifically targets the most toxic, oligomeric forms of Aβ and ptau, has the greatest chance of success with little risk of toxicity.
Presenter: Fernando Goni, PhD, research associate professor, Department of Neurology, Division of Aging and Dementia, NYU School of Medicine
Embargoed for Release until Thursday, July 18 2013 - 11:30AM - 1:00PM ET
Poster Presentations
Saturday, July 13th
Alzheimer's Imaging Consortium Postmortem Study of Hippocampus Subfields and Layers at 7T MR (Poster)
Authors-Mohammad Yazdanie, Yulin Ge, Youssef Zaim Wadghiri, Mony de Leon, Thomas Wisniewski
Introduction: Atrophy of the hippocampus is a key pathological hallmark of Alzheimer's disease (AD). An interest of subfields of hippocampal imaging has emerged in recent years due to the advent of ultra-high field MR. This work was to evaluate the imaging parameters on human postmortem brain at 7T MR using 3D susceptibility-sensitivity imaging (SWI) with enhanced tissue susceptibility contrast to better identify these layers and hippocampal subfields that are not available on conventional MR in order to better understand the transition of the hippocampus in AD as disease progresses.
Conclusion: Due to the markedly enhanced susceptibility contrast at ultra-high-field MR, the cell types in hippocampus showed different intensities with enhanced identification of structural borders that allow us to visualize the hippocampal structural layers and subfields.
Clinical Relevance/Application: Ultra-high-field MR may provide a noninvasive direct detection and quantification of hippocampal substructural changes to monitor the disease progression in vivo human brain. Presenter – Yulin Ge, MD, associate professor, Department of Radiology, NYU Langone Medical Center
Embargoed for Release until Saturday, July 13, 2013 from 12:30pm-2:30pm
Sunday, July 14, 2013
Memantine and Comprehensive, Individualized, Person Centered Management (CI-PCM) of Alzheimer's Disease: A Randomized Controlled Trial. (Poster)
Authors- Reisberg, B., Kenowsky, S., Boksay, I., Golomb, J., Heller, S., Ghimire, S., Salam, M., Qureshi, S., Kumar, M., Torrosian, C., and Vedvyas, A.,
Background: Demonstration of efficacy of memantine treatment for persons with moderate to severe Alzheimer's disease (AD) over 28 weeks highlighted both treatment possibilities and treatment needs of persons with advanced AD. In prior work, we developed a science of AD management, based upon scientific observations of the retrogenesis process and other pathologic AD processes. Herein, we investigated the hypothesis that application of this AD management science would result in improved outcomes beyond those with pharmacologic treatment alone.
Conclusion: These initial results strongly demonstrate the very large added benefit of our CI-PCM program in the treatment of persons with moderate to severe AD. At all time points, memantine plus management subjects showed global improvements, and memantine with financial compensation subjects showed continuing global decrements. We demonstrate that a science of care management can add to medication effects alone by a magnitude of nearly 800%.
Presenter - Barry Reisberg, MD, professor, Department of Psychiatry; director, Fisher Alzheimer's Disease Program; clinical director, Aging & Dementia Clinical Research Center; director, Clinical Core, NYU Alzheimer's Disease Center, Comprehensive Center on Brain Aging; NYU Langone Medical Center
Embargoed for Release until Sunday, July 14, 2013 from 11:45Am - 2:15PM
Monday, July 15, 2013
MRI and FDG-PET Changes in Normal Aging Across the Adult Lifespan (Poster)
Background: A great deal of current research is aiming to better understand what happens to brains affected by Alzheimer's disease, both structurally and metabolically. However, little is known about how the brain ages in the cognitively normal adult population. There is also a limited understanding as to how glucose metabolism and brain atrophy interact in the normal human brain. To our knowledge, this study is the first to longitudinally analyze measures of atrophy and metabolism in both MRI and FDG-PET in cognitively normal subjects.
Conclusions: Our results show that brain atrophy increases over the adult lifespan. These changes appear to accelerate over time. However, metabolically, we did not find any significant results with regard to change over time. This is in contrast to Alzheimer's disease, where literature has shown metabolic decreases in frontal and parietal regions, particularly in precuneus/posterior cingulate. Our results also illustrate the importance of controlling for structural atrophy in FDG-PET.
Presenter: Alex Goldowsky, study coordinator, Center for Brain Health
Embargoed for Release until Monday July 15, 2013 at 11:45AM – 2:15PM ET
Tuesday, July 16, 2013
White Matter Degeneration in Early and Late-Myelinating Tracts Through the Course of Alzheimer's disease (Poster)
Authors - Els Fieremans, Andreana Benitez, Jens H Jensen, Maria F Falangola, Ali Tabesh, Rachael L Deardorff, James S Babb, Dmitry S Novikov, and Joseph A Helpern
Background: We recently introduced diffusional kurtosis imaging (DKI)-derived metrics of white matter tract integrity (WMTI), which differentiated controls, MCI, and AD with high diagnostic accuracy2. Here we applied these WMTI metrics to the study of AD progression within the framework of retrogenesis. We correlated these metrics with verbal fluency, a cognitive function mediated by late-myelinating association fibers known to be affected in AD.
Conclusion: Our results highlight the importance of WM changes in addition to gray matter pathology in the study of AD. Future work with larger samples should verify these findings using a longitudinal design.
Presenter - Els Fieremans, PhD, assistant professor, Department of Radiology, Center for Biomedical Imaging, NYU School of Medicine/NYU Langone Medical Center
Embargoed until Tuesday, July 16, 2013: 11:45am – 2:15pm ET
Tuesday, July 16, 2013
Topic: Public Health and Psychosocial
Subtopic: Epidemiology of Risk Factors of Alzheimer's disease
Project Learn MORE: Expanding Service Usage of Individuals with Early Stage Alzheimer's Disease (Poster)
Background: The Missouri Department of Health and Senior Services, the four Missouri Alzheimer's Association Chapters and ten Area Agencies on Aging (AAA's) collaborated in a two-year study to increase usage of available services by Missourians with Alzheimer's disease. Project Learn MORE (Missouri Outreach and Referral Expanded) proposed using the AD8 Dementia Screen by AAA caseworkers to detect incident cases, and referral of persons with dementia (PWDs) and family caregivers to Alzheimer Association chapters to receive supportive services and an intervention to increase coping skills.
Presenter: James E. Galvin, MD, MPH, professor, Departments of Population Health, Psychiatry and Neurology, Comprehensive Center on Brain Aging, NYU Langone Medical Center
Embargoed for Release until Tuesday, July 16, 2013, 11:45 AM ET
###
Reporter note: Abstracts are available as well as researcher contact numbers. Additionally, we would be delighted to provide you with experts who are attending the conference and can provide insight and commentary on research presentations and findings. Please contact me for additional information or a contact master list.
About The Comprehensive Center on Brain Aging
The Comprehensive Center on Brain Aging (http://aging.med.nyu.edu/) is devoted to healthy brain aging through the understanding, treatment, cure and prevention of aging-related cognitive decline by way of translational research, education and evidence-based geriatric care. Founded upon the strengths of the Silberstein Alzheimer's Institute, its broad-scale research program is focused on Alzheimer's disease and memory disorders; Parkinson's disease and movement disorders; atypical dementias; geriatric psychiatry and neurology, and healthy brain aging. The Pearl I. Barlow Center for Memory Evaluation and Treatment encompasses services for diagnosis and management of Alzheimer's disease and memory disorders of all origins, as well as novel programs (cognitive remediation and falls prevention) and specialty clinics, including those devoted to non-Alzheimer's disease dementias and Prion diseases, and Lewy Body Dementia. These clinics are the only ones of their kind in New York City.
About NYU Langone Medical Center
NYU Langone Medical Center, a world-class, patient-centered, integrated, academic medical center, is one on the nation's premier centers for excellence in clinical care, biomedical research and medical education. Located in the heart of Manhattan, NYU Langone is composed of four hospitals – Tisch Hospital, its flagship acute care facility; the Hospital for Joint Diseases, one of only five hospitals in the nation dedicated to orthopaedics and rheumatology; Hassenfeld Pediatric Center, a comprehensive pediatric hospital supporting a full array of children's health services; and the Rusk Institute of Rehabilitation Medicine, the world's first university-affiliated facility devoted entirely to rehabilitation medicine– plus NYU School of Medicine, which since 1841 has trained thousands of physicians and scientists who have helped to shape the course of medical history. The medical center's tri-fold mission to serve, teach and discover is achieved 365 days a year through the seamless integration of a culture devoted to excellence in patient care, education and research. For more information, go to http://www.NYULMC.org.
END