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Alzheimer's Disease-Related Dementias: Research Challenges and Opportunities


Sponsored by:

National Institute of Neurological Disorders and Stroke

In collaboration with:

National Institute on Aging

Meeting Dates:

May 1-2, 2013


Natcher Auditorium
Bethesda, Maryland
United States


The ADRD workshop addressed special research priorities for Alzheimer's disease-related dementias, including frontotemperal (FTD), Lewy body (LBD), mixed, and vascular dementia. Organized by the NINDS in collaboration with the National Institute on Aging (NIA), the workshop is part of the 2012 National Plan to Address Alzheimer's Disease, and is complementary to NIA's Alzheimer's Disease Research Summit 2012.

The 2013 ADRD workshop and the final approved recommendations reflect the outcome of the pre-workshop, workshop, and post-workshop efforts. Prioritized research recommendations and timelines have been divided into five topic areas: multiple etiology dementias, health disparities, FTD, LBD, and vascular contributions to ADRD. Each prioritized recommendation includes a timeline that indicates anticipated time to completion, or implementation of fully operational status.

All recommendations listed in the final report represent very important research goals. Indeed, to be included in this report means that research goal is among the top items in its respective field. The timelines represent the intervals from now to expected completion or full implementation, if resources are available to start immediately, and are independent of prioritization. There are several reasons why one recommendation might be expected to take longer than another, however, longer time to completion or full implementation does not diminish a recommendation's priority.


Roderick A. Corriveau, Ph.D.
Program Director, Neurodegeneration

Links & Resources

Prioritized Recommendations

Prepared by Dr. Thomas Montine on behalf of the ADRD 2013 Committees
Approved by NINDS Council, 9/12/2013
Submitted to the NAPA Council, 12/2/2013
Prioritized recommendations are numbered in rank order

Introduction to the Recommendations – Excerpt from pp. 3-4 of the ADRD 2013 Report:

The following report reflects the outcome of our pre-workshop, workshop, and post-workshop efforts. We have divided our prioritized research recommendations and timelines into five topic areas. Two topic areas are fundamental to all ADRDs; and although beyond the scope of our charge, in our opinion, they also are relevant to AD itself: diagnosis and epidemiology of multiple etiologic dementias, and disparities populations. The other three topic areas are disease-specific: FTD, LBD, and vascular contributions to ADRD (VAS).

The format of prioritized research recommendations differs somewhat among the five topic areas. The decision to allow this was deliberate, and has the goal of not unnecessarily constraining optimal prioritization within each topic area. Timelines were made uniform across topic areas (1-3 yr, 3-7 yr, 7-10 yr, or > 10 yr) and reflect time to completion or achieving fully operational status for the recommendation.

Two points need to be stressed:

  • All recommendations in this report are very important research goals. Topic session committees were charged with the difficult task of assigning priority within each area. However, this should not be misinterpreted as indicating that any recommendation is unimportant. Indeed, simply to be included in this report means that research goal is among the top items in its respective field.

  • Our timelines are the interval from now to expected completion or full implementation, and are independent of prioritization. There are several reasons why one recommendation might be expected to take longer than another, e.g., more work needs to be done, other goals need to be accomplished first before full success can be achieved. However, longer time to completion or full implementation does not diminish priority and should not be misconstrued as an option to delay onset of work; in fact, just the opposite.

As Scientific Chair of the ADRD Workshop, I respectfully submit this report to NINDS Council on behalf of all committee co-Chairs and members.


The signature of Thomas J. Montine, MD, PhD

Thomas J. Montine, MD, PhD
Alvord Professor and Chair
Department of Pathology
University of Washington

ADRD Recommendations: Excerpt from the ADRD 2013 Report, pp. 9-19:

Topic 1 - Multiple Etiology Dementias: The Public Health Problem and Improving Recognition across the Spectrum

Focus Area 1 - Differential Diagnosis

Recommendation 1. Develop clinical algorithms for detection of prototypical neurodegenerative dementias and VCI in (a) primary care, (b) general neurology, and (c) general psychiatry outpatient settings; and clinical algorithms for referral to specialists in appropriate cases that also might involve consultations using novel technologies (1-3 yr).

  • Diagnosis of ADRDs can be challenging; however, advances have occurred in the definition of clinically important features that distinguish the dementia of AD from VCI, LBD, behavior variant FTD, primary progressive aphasia, normal pressure hydrocephalus, and prion disease, as well as other rapidly progressive dementias and syndromes with multiple neurodegenerative and vascular elements. "Prototypical" presentations of each of these can be defined on clinical grounds and employed as exemplars.

  • Because most people with disorders in the dementia spectrum are not evaluated by specialists and treatments are most effective in the earliest stages of disease, there is a pressing need to translate new advances in diagnoses and care to where the majority of cognitive disorders present: primary care, general neurology, and general psychiatry outpatient practice. Detection of the prototypical presentations by such first line clinicians must be emphasized.

  • New approaches to diagnosis of cognitive disorders in primary care should be pursued and evaluated using rigorous criteria for effectiveness. These approaches would include standardized informant-based electronic questionnaires, easily accessible telemedicine consults with specialists, and other electronically supported diagnostic aids.

  • There is currently a critical shortage of cognitive specialists and researchers to develop innovative treatments and direct systems of care for persons with dementia. It is therefore imperative to support high quality clinical research training programs that attract physicians and non-physician researchers in geriatrics, behavioral neurology, and geriatric psychiatry.

  • Because the problem of dementia crosses multiple disciplines, collaboration among the appropriate planning and funding agencies, both internationally and nationally, including among different Institutes of the NIH, is critical to successfully solve this major public health problem.

Recommendation 2. Develop imaging and fluid biomarker algorithms to detect prototypical versus atypical dementias and expand their accessibility in primary care settings (3-7 yr).

  • Despite gains in clinical recognition, clinical diagnostic tools alone will be insufficient to capture the full range of etiologies in many individuals with dementia. Two reasons are that most late life cognitive impairment is multiple etiologic, and specific diseases do not exclusively map to only one clinical presentation. For example, VCI can present with a variety of cognitive syndromes. Additionally, behavior variant FTD may be due to one of several distinct molecular drivers. The field needs to embrace such complexity, as reductionist approaches simply do not fit reality. An improved conceptual framework for, and improved practical approaches to, multiple etiology dementia must be developed.

  • Imaging and fluid biomarkers are needed to provide evidence for different etiologies, whose presence might not be provable on clinical grounds alone. Validation of biomarkers will require large-scale testing in well-studied patients.

  • A considerable fraction of patients who are clinically diagnosed with AD dementia have other diseases causing dementia alone or in combination with AD. Understanding the contribution of non-AD etiologies to AD pathophysiologic processes is essential.

  • Neuroimaging plays a special role in dementia diagnosis. Expertise in the neuroradiology of dementing illnesses is currently limited to tertiary care facilities. Yet methods exist for automating some aspects of neuroimaging. Algorithms for analyzing brain imaging (structural magnetic resonance [MR], single-photon emission computed tomography, positron emission tomography) need to be available for all radiologists and non-radiologists when interpreting brain scans when there is clinical suspicion of dementia. Validation would also need to be provided by neuropathologic evaluation.

Recommendation 3. Develop clinical, imaging, and fluid biomarker algorithms for the rapidly progressive and potentially treatable dementias to enable recognition and referral to specialists (1-3 yr).

  • Because of their relative rarity, the rapidly progressive (e.g., prion disease) and potentially treatable (e.g., non-infectious autoimmune encephalopathies, normal pressure hydrocephalus) dementias are very challenging to diagnose outside of specialty settings.

  • Particularly with the autoimmune encephalopathies, responsiveness to therapeutic interventions requires timely detection and recognition in the earliest stages by primary care practitioners and general neurologists.

  • Algorithms and detection protocols based on a combination of clinical, imaging, and fluid biomarker assessments should be developed for deployment in primary care and general neurology settings. (See Recommendation 1 above for validation of these algorithms and detection protocols).

Focus Area 2 - Epidemiology

Recommendation 1. Conduct population-based studies of dementia prevalence and incidence in diverse ethnic groups and age ranges using imaging and fluid biomarkers (1-3 yr).

  • Many of the non-AD dementias occur in people under 70 years old, and there is considerable uncertainty about the accuracy of current estimates of the prevalence or incidence of behavioral variant FTD, primary progressive aphasia, Lewy body diseases, normal pressure hydrocephalus, and the rapidly progressive dementias.

  • Almost all of the currently available estimates of incidence and prevalence of diseases that cause dementia have utilized the single diagnosis model for reporting results. Future studies should develop the capability of reporting prevalence and incidence in terms of multiple etiology.

  • The next generation of population-based studies should utilize currently available imaging and fluid biomarker assessments to allow more refined and complete assessments of etiology(ies), and also serve as test-beds for identification and validation of new biomarkers.

  • The next generation of population-based studies must involve diverse ethnic groups, due to potential differences in risk factors for dementia and in response to therapies.

Recommendation 2. Develop registries for enumerating and characterizing less common dementias, dementias in younger persons, rapidly progressive dementias, and potentially treatable dementias (1-3 yr).

  • Use electronic medical records within large regional health systems to screen populations and develop registries of people with cognitive impairment. This approach complements traditionally designed epidemiological studies by reflecting the actual stress that cognitive disorders place on the healthcare system and expands research opportunities in community settings.

  • Efficient data acquisition, supplemented by technologies described in Recommendation 1 in the Differential Diagnosis Focus Area, is a critical design requirement to avoid over- burdening primary care providers.

  • Registries should link clinical diagnoses to later neuropathologic findings.

Recommendation 3. Expand and broaden the accessibility of neuropathology services to cases of cognitive impairment and dementia outside of research centers. Link neuropathologic findings to development of clinical algorithms and biomarkers (1-3 yr).

  • Until imaging and fluid biomarkers are "qualified" as valid for the diagnosis of specific dementia etiologies, post-mortem neuropathologic examinations remain essential for verifying underlying disease processes when testing imaging and fluid biomarkers and clinical algorithms.

  • Because anatomic pathology is grossly underfunded in modern health care systems, neuropathology as a subspecialty is under great stress. Neuropathology is an absolutely essential core infrastructure for research in neurodegenerative and late-life cerebrovascular diseases, and is the foundation for improving clinical diagnoses and aiding in better understanding the prevalence of the non-AD dementias.

Topic 2 - Health Disparities

Focus Area 1 – Recruitment

Recommendation 1. Initiate and leverage ongoing longitudinal community-based cohort studies of incident dementia in diverse populations incorporating imaging, fluid biomarkers, and autopsy (3-5 yr).

  • Enroll people without known dementia at baseline in order to provide data on the full spectrum of cognition and to examine the transition from no cognitive impairment to dementia, or leverage prior data collection efforts by building on existing community- based cohort studies by adding careful ADRD assessments and biobanking initiatives.

  • Use recruitment strategies that are community- rather than clinic-based to reduce bias, including recruiting persons with a range of co-morbidities.

  • Include individuals representing demographic diversity with respect to race/ethnicity, rurality, socioeconomic status, and life experiences in order to make cohorts as representative as possible.

  • Assess a wide range of risk factors and incorporate cutting-edge imaging and fluid biomarkers (both blood and CSF) and autopsy when possible.

  • Biobank a wide range of ante- and post-mortem biospecimens for future studies.

Recommendation 2. Use mixed methodology studies to improve assessment tools for disparities populations (1-3 yr).

  • Due to language differences, varied cultural beliefs about cognitive decline and normative expectations for behavior among older people, as well as differing attitudes about discussing potentially stigmatizing illnesses with non-family members, there is great need for assessment tools developed for and validated among disparities populations.

  • Generate a repository of assessment tools (i.e., questionnaires, neuropsychological instruments and normative references, and informant-based surveys) validated for use among diverse populations.

  • Pool existing (global and item-level) data from ongoing or previously conducted studies of aging that include diverse populations for advanced psychometric analyses (e.g., Item Response Theory) and for generation of normative references.

  • Conduct studies using community-based approaches adopting both qualitative and quantitative methods to ascertain how disparities populations understand the behavioral and cognitive changes specific to ADRDs along with appropriate methods for collecting informant-based assessments of daily functioning levels.

  • Conduct validity studies of newly generated instruments among diverse patients.

  • Embed culturally- and linguistically-appropriate assessment tools within ongoing and newly generated studies of ADRDs.

Recommendation 3. Use community outreach methods to facilitate recruiting disparities populations into FTD and LBD clinical studies (5-7 yr).

  • Address many reasons for low rate of research participation, including inadequate connection with health systems, screening, and diagnosis; low knowledge; alternative health beliefs; and distrust of research.

  • Use Community Advisory Boards to involve local leadership, partner with local institutions for recognition and access, use educational programing to improve case detection, and provide practical resources (e.g., transportation) for intensive community outreach.

  • Develop simple, sensitive methods for screening for cognitive impairment and dementia in primary care settings.

  • Leverage local initiatives/agencies sponsoring collaborative, community-driven plans that are focused on health outcomes in disparities populations.

Recommendation 4. Evaluate under-diagnosis and implement surveillance for ADRDs to detect incidence and monitor trends in disparities populations (5-7 yr).

  • Identify barriers to diagnosis to understand the burden of disease for ADRDs, for example, via research on predictors of under-diagnosis, evaluate whether disparities populations have similar diagnosis rates.

  • Develop surveillance approaches using information gained from these studies.

  • Build these studies into other research approaches, provided data linkages are available and time-to-diagnosis questions are implemented.

Focus Area 2 - Advancing Treatment and Prevention Strategies

Recommendation 1. Enhance the design of all trials of vascular health interventions to improve their application to diverse populations (5-7 yr).

  • Evidence exists that vascular health is critical to delaying onset of dementia, potentially not only VCI/VaD, but also LBD and AD, and may be differential across diverse populations.

  • Intervention trials for cardiovascular and stroke outcomes could provide valuable secondary evidence on prevention of dementia, if high-quality standardized cognitive outcomes are included.

  • Adopt high-quality neurologic assessments (e.g., imaging, neuropsychological, and autopsy data) in the design of vascular health intervention trials.

  • Appropriately design proposed interventions that are culturally sensitive to ensure their application to diverse populations.

  • Prioritize diversity recruitment, with over-representation of certain populations to permit stratified or effect modification analyses.

  • Adopt standardized assessments to facilitate meta-analyses and enhance the value of the evidence across these trials.

Recommendation 2. Assess lifecourse risk factors for cognitive decline and ADRDs among disparities populations (1-3 yr).

  • Cognitive decline appears to be greater for disparities populations where there are well- established higher risk factor profiles, but much observational research does not define exposures that closely correspond with potential treatments or interventions.

  • Measure changes in risk factors (both traditional and novel) over the lifecourse and link to assessments of adult cognitive status and ADRD outcomes.

  • Assess whether interventions that change the risk factors predict reduced rates of cognitive decline or risk of dementia across dimensions of race/ethnicity, socio-economic status, and rural living.

Recommendation 3. Estimate disparities in health burden of ADRDs and risk factors among disparities populations (1-3 yr).

  • To prioritize public health interventions and campaigns, obtain estimates of incidence of ADRDs and the population-attributable fractions for specific risk factors.

  • Both the prevalence and impact of many risk factors may differ across disparities populations.

  • It is currently unknown whether vascular disease makes a larger contribution to all-cause dementia in disparities populations; however, this is likely to be the case because prevalence of several vascular risk factors and stroke differs across groups.

Recommendation 4. Identify environmental and genetic factors that modify incidence, presentation, and long-term outcomes of ADRDs in disparities populations (>10 yr).

  • Environmental contexts often differ markedly across all disparities populations.

  • Prevalence of some risk genetic alleles may differ by race/ethnicity and the impact of the same genetic locus on ADRD outcomes may differ across social context.

  • Test the intersection of social and biological mechanisms of dementias to see if mechanisms differ across populations (e.g., vascular processes may play a larger role in disparities populations because of the greater prevalence of many vascular risk factors).

  • Genetic studies should include diverse populations and incorporate measures of environmental factors that are differentially patterned across disparities populations, recognizing that "race" correlates with both genetic ancestry and countless social factors; many of these social variables are independent risk factors for some ADRD outcomes, so genetic research must account for social conditions.

  • Use this genetic research to identify opportunities to prevent or treat the dementias.

Topic 3 - Lewy Body Dementias (LBD): Dementia with Lewy Bodies (DLB) and Parkinson's Disease Dementia (PDD)

Focus Area 1 - Establish Longitudinal Cohorts with Common Measures, Culminating in Autopsy Studies

Recommendation 1. Initiate clinical trials for DLB and PDD using existing and newly developed symptomatic therapies that address key symptoms that impact patient function and the burden put on caregivers (1-3 yr).

  • While there have been many therapeutic trials focused on PD, patients with dementia (DLB and PDD) have been excluded. Consequently, there is little information about the efficacy of approved drugs, (e.g., dopamine replacement) and experimental drugs on DLB and PDD. The aim of this recommendation is to engage existing clinical networks, such as the Alzheimer's Disease Cooperative Study, Parkinson Study Group, or NeuroNEXT, and to establish new networks of clinicians, including movement disorder specialists, behavioral neurologists, psychiatrists, or sleep disorder specialists, to use well-characterized cohorts of DLB and PDD for treatment trials with current Food and Drug Administration-approved drugs.

Recommendation 2. Create longitudinal clinical, biological, and imaging resources for DLB and PDD from the earliest stages to autopsy studies to improve the accuracy of detection and diagnosis of DLB at the pre-dementia or prodromal stage and to detect PD patients with a high risk of cognitive decline leading to PDD (1-3 yr).

  • DLB is currently under-diagnosed compared with AD and the diagnosis is often made too late to allow optimal symptomatic management and prevention when suitable agents become available. The aim of this recommendation is to capitalize on existing longitudinal cohorts studying late life dementia disorders, such as the Alzheimer's Disease Neuroimaging Initiative, by enriching the population with individuals with potential early manifestations of DLB, including dream enactment behavior (also known as rapid eye movement sleep behavior disorder), hyposmia, autonomic dysfunction, and non-amnestic mild cognitive impairment.

  • Although the majority of PD patients, if followed long enough, will develop dementia, the time from the onset of motor symptoms to dementia varies markedly. Dementia in PD has a major impact on function, quality of life, and medical costs. Although some potentially predictive demographic and clinical factors are known for PDD, such as older age of onset of PD or a postural instability/gait disorder clinical subtype of PD, very few prospective biomarker studies exist. Such biomarkers may provide insight into the mechanisms leading to cognitive decline in PD and thus represent future therapeutic markers.

Focus Area 2 - Discover Disease Mechanisms through Brain Mapping and Genetics

Recommendation 3. Using well defined cohorts with DLB or PDD who have come to autopsy, systematically map disease-specific changes in the brain, spinal cord, and peripheral autonomic nervous system with state-of-the-art methods, including genomics, expression arrays, metabolomics, and proteomics to identify underlying disease mechanisms that will guide future biomarker and therapeutic approaches (1-3 yr).

  • Require that data generated in this mapping initiative be incorporated into an open- access database that links clinical, biological, and autopsy data.

Recommendation 4. Identify novel common and rare genetic variants, epigenetic changes, and environmental influences that influence the risk and clinical features of DLB and PDD (5-7 yr).

  • This goal will require genome-wide association studies of large cohorts, as well as whole exome/genome sequencing of families with multiple affected members. This recommendation also includes identification of genetic and epigenetic factors influencing the risk of developing dementia or Lewy body disease in patients with PD or other degenerative diseases. Genetic studies should lead to the development of diagnostics, such as a panel of common genetic variants or gene expression profiling, to enable the stratification of patients by diagnosis, and with respect to prognosis and response to treatment. Studies should also be developed that study gene-environment interactions.

Focus Area 3 - Develop and Validate Biological and Imaging Biomarkers

Recommendation 5. Develop imaging approaches to enhance the diagnostic accuracy of DLB and PDD, detect latent and prodromal DLB and PDD, and monitor disease progression in natural history and treatment studies by integrating established and new imaging tools (5-7 yr).

  • Evaluate role of currently available imaging tools in the diagnosis and classification of these disorders with emphasis on imaging modalities demonstrating high reproducibility across populations, scanning sites, and imaging platforms.

  • Develop parallel strategies to evaluate emerging technologies or analytical approaches for feasibility and value added in a multicenter trial environment. This approach will additionally facilitate the development of synergistic multi-modal biomarker strategies (e.g., α-synuclein binding agent) in combination with systems-level functional biomarkers of disease severity to enhance the accuracy of diagnosis and the reliability of progression measurements early in disease course.

Recommendation 6. Use existing or new longitudinal case-control studies of individuals with DLB and PDD to develop biomarkers for Lewy-related pathologic changes, disease progression, and the relative amount of concurrent AD. As new markers of molecular disease mechanisms are discovered, incorporate them into biomarker studies for diagnosis of latent or prodromal disease and for monitoring molecular processes and their response to therapies (5-7 yr).

This recommendation proposes to capitalize on existing longitudinal case-control cohorts to encourage standardization of protocols and core data elements. Clinical data should be linked to biobanks of fluids, tissues, and other biomaterials collected on the cohort through an open access database to foster biomarker development. Biomarkers are needed not only to detect PD but also PD pathologic changes, markers of neurodegeneration, and markers of disease risk

Focus Area 4 - Model Disease Processes to Develop Potential Symptomatic and Disease Modifying Therapies

Recommendation 7. Recognizing the importance of α-synuclein and AD pathophysiologic processes in DLB and PDD, new animal, cellular, and in vitro models are needed that recapitulate key features of these disorders with the ultimate goal of identifying strategies that can be carried forward into clinical trials (3-7 yr).

  • This recommendation recognizes the need to develop models that fit not only what is known about the molecular pathology of DLB and PDD based upon current evidence, but also what can be learned from proposed systematic mapping and biomarker studies. New models will enhance understanding of selective vulnerability; mechanisms of neurotoxicity; factors that determine disease progression, transmission or propagation; and how to design and test therapeutic interventions.

  • Ideally, new animal, cellular and in vitro models will incorporate new research discoveries and may include the use of human materials, such as induced pluripotent stem cells (iPS cells) from subjects enrolled in clinical, genetic, or biomarkers studies.

Recommendation 8. Develop disease-modifying interventions based upon research discoveries (7-10 yr).

  • This recommendation builds upon the knowledge base that is gained from genetic studies and from systematic profiling of well-characterized patient samples that identify underlying disease mechanisms. The long-range goal is to use therapeutic approaches that prevent or alter the disease processes using pharmaceutical approaches, gene therapy, regenerative medicine, or surgical interventions.

Topic 4 - FTD and Related Tauopathies

Focus Area 1 - Basic Science: Pathogenesis and Toxicity

Recommendation 1. Clarify the mechanism of tau pathogenesis and associated neurodegeneration (3-7 yr)

  • The mechanism of tau driven neurotoxicity and its relationship to the formation and spreading of tau pathological inclusions needs to be determined in order to identify optimal therapeutic approaches. In particular, which pathophysiological events (post- translational tau modifications, aggregation, microtubule dysfunction, interneuronal spread, or other tau (dys)functions) represent the most human-relevant, deleterious, and targetable processes?

  • Innovative cell-based, animal model, and human post-mortem studies are the recommended approaches to determine pathogenic events that promote tau toxicity and spread. Genetic models should be complemented with other methods that may simulate aspects of sporadic disease (inoculation studies, iPSCs, etc.).

Recommendation 2. Develop better FTD in vivo and cell-based model systems (1-3 yr)

  • There is a need to improve the tools for disease mechanism and target identification, validation, and drug development. Do existing FTD models reproduce the formation of pathological lesions, associated neurodegeneration, and behavioral impairment?

  • The recommended approach is to prioritize development of robust models to study TDP- 43/FUS, GRN haploinsufficiency, and C9ORF72 expansion disease, using emerging behavioral and pathological features of human disease as the standard for comparison once those features are systematically defined. In addition, continue to evaluate transgenic models of tauopathy and revisit genomic tau transgenes and knock-in models, emphasize use of FTD-relevant behavioral and motor assays and models with mild clinical phenotypes (e.g., GRN mutation heterozygous mice), and develop human iPSC models for genetic and sporadic disease to enable molecular dissection of pathogenesis.

Recommendation 3. Determine the molecular basis for C9ORF72 expansion- and GRN-related neurodegeneration (3-7 yr)

  • There is need to identify the predominant mechanism(s) of C9ORF72 FTD/ALS pathogenesis: loss of gene function, RNA toxicity, dipeptide repeat toxicity, TDP-43 proteinopathy, or other factors, and to determine the mechanisms of neurodegeneration in GRN-related FTD: TDP-43 proteinopathy, neuroinflammation, or other mechanisms.

  • The recommended approach is to expand the scope and precision of human neuropathologic studies of C9ORF72 and GRN mutation carriers to address which pathologic features correlate best with neurodegeneration. In addition, compare human findings with those derived from animal and cell-based models and test treatments for different aspects of mutation-related pathogenesis in model systems, for example, by exploring RNA lowering strategies for C9ORF72-related disease or anti-inflammatory approaches to GRN-related disease. Finally, determine the normal function of progranulin, especially during the response to brain injury, how haploinsufficiency leads to neurodegeneration, and identify therapeutic approaches designed to replace/increase GRN.

Recommendation 4. Determine the mechanism of TDP-43 and FUS pathogenesis and toxicity (3-7 yr).

  • There is need to clarify fundamental disease mechanisms associated with the TDP-43 and FUS proteinopathies. Do TDP-43/FUS represent toxic, spreading disease proteins? Does loss of protein function play a significant role? Is intraneuronal progression unified across TDP-43 pathologies and what is the sequence of events?
    Our recommended approach is to expand the scope and precision of human neuropathologic studies, focusing on early-stage disease, define the sequence of molecular changes associated with pathogenesis from loss of nuclear localization to the formation of assemblies, and continue to study and define the normal cellular functions of TDP-43 and FUS.

Focus Area 2 - Clinical Science: FTD Clinical Discovery, Tools, and Cohorts

Recommendation 1. Expand efforts to genotype patients with FTD and identify new genes (1-3 yr).

  • There is need to accelerate discovery of new familial FTD genes and provide genotyping support for research on patients with known genetic profiles, whether or not a disease- causing mutation is present.

  • Our recommended approach is to provide increased clinical resources to identify and collect FTD families with a range of phenotypes, create core service for FTD genotyping and banking DNA where any researcher can send samples, receive genotype information, or request data/samples from large cohorts. Improve access and cost of screening for FTD genes, and support GWAS with deep sequencing around subthreshold peaks. These efforts should include amyotrophic lateral sclerosis (ALS) kindreds in gene discovery studies.

Recommendation 2. Develop FTD biomarkers for diagnosis and disease progression (3-7 yr).

  • There is need for better tools to detect early stage disease, establishing molecular diagnosis, monitoring disease progression, and measuring therapeutic efficacy.

  • Our recommended approach is to develop molecular biomarkers (PET/CSF/blood measures) for molecular diagnosis of FTLD-tau, -TDP, and –FUS, with a priority on tau. These efforts will segment clinical trial cohorts and ultimately enable tailored FTD therapy. These studies should be complemented by efforts to define the most sensitive systems-level surrogate outcome biomarkers (MRI/fMRI/PET/EEG/clinical) for monitoring progression during early stage disease, seeking to inform early clinical proof- of-concept studies and ultimately minimize sample size requirements in Phase III clinical trials. In addition, there is need to identify the most meaningful clinical endpoints for Phase III trials, determine whether recently identified tau PET tracers will detect tau pathology in FTD and related tauopathies, as well as in AD, and pursue deeper motor phenotyping to detect emergence of motor neuron disease (MND), as this will impact natural history.

Recommendation 3. Create an international FTD clinical trial network (1-3 yr).

  • There is need to facilitate orchestration of impending FTD clinical trials.

  • Our recommended approach is to establish an international network of FTD clinical experts to ascertain FTD cohorts and collect clinical, genetic, and biomarker data using a centralized database/coordinating center. These data should be used to refine disease models, clinical endpoints, and trial design.

  • We recommend prioritization of clinical studies with therapies designed to replace/increase GRN.

Recommendation 4. Understand phenotypic heterogeneity and natural history (>10 yr).

  • There is need to understand how genetic background, brain development, and environment are linked to the patient's clinico-pathologic syndrome and what factors influence onset age and pace of progression. Understanding these factors may enhance trial design by accounting for variations in anatomical and temporal progression across cohorts and will aid interpretation of trial outcomes.

  • Our recommended approach is to conduct natural history studies of preclinical inherited FTD (especially MAPT, GRN, and C9ORF72-related FTD) by following individuals from health to disease. In addition, we recommend pursuing parallel longitudinal studies of patients with sporadic FTD, starting from early symptomatic FTD and prioritizing clinical syndromes for which the clinico-pathologic correlation is high (e.g., progressive supranuclear palsy and tau, semantic variant primary progressive aphasia and TDP-43 Type C, FTD with MND and TDP-43 Type B). We recommend seeking genetic, anatomic, and environmental disease modifiers that influence clinico-pathologic heterogeneity across inherited and sporadic cohorts. Finally, we recommend using cohorts to support longitudinal biomarker discovery and identify optimal clinical trial endpoints, considering the Dominantly Inherited Alzheimer's disease Network (DIAN) as a model.

Topic 5 - Vascular Contributions to ADRD: Focus on Small Vessel Disease and AD/Vascular Interactions

Focus Area 1 - Basic Mechanisms and Experimental Models

Recommendation 1. Develop next-generation experimental models of VCI and VaD (3-7y).

  • Animal model and human studies (clinical, genetic, pathological, imaging, etc.) should be designed to inform each other from the cellular to the systems level.

  • Because of the pathogenic diversity of VCI/VaD syndromes, multiple models, each recapitulating key features of a specific human disease process, are needed.

  • In particular, establish animal models that reproduce small vessel disease and other key pathogenic processes thought to result in cognitive impairment, e.g., models of chronic blood-brain barrier breakdown such as those caused by disrupted endothelial-pericyte or endothelial-astrocyte signaling and models of hypoperfusion.

  • Such rodent models should also easily be applied to AD research, so VCI/VaD and AD can be studied individually and in combination, e.g., models with deletion of genes from vascular cells such as endothelial cells, pericytes, and vascular smooth muscle cells.

  • Use such animal models to increase our knowledge of lifestyle risk factors.

  • Develop new tools for cell- (endothelial, smooth muscle, pericyte, etc.) and region- (gray vs. white matter, cortex vs. striatum, etc.) specific genotyping and phenotyping of the cerebrovascular tree and neurovascular unit (glia, immune cells, etc.).

  • Test the effect of pathogenic factors on cerebral blood vessels and how these impact brain function at the synaptic, neuronal, network, systems, and behavioral levels, and in gray or white matter.

Recommendation 2. Encourage basic science research that investigates the impact of AD risk factors on cerebrovascular function (3-7 y).

  • Encourage basic research that intentionally investigates interactions among risk factors for dementia and cerebrovascular function, so as to generate preclinical data with increased translational potential. The largest risk factors for AD remain age and apolipoprotein E genotype (APOE), yet they are not consistently modeled in many preclinical studies focused solely on Aβ-mediated effects in young to middle-aged mice fed a far healthier diet than most North Americans consume. Key areas for further research include:
    • Investigate Aβ-mediated effects on cerebrovascular function, including all cells involved in the neurovascular unit.
    • Investigate Aβ-mediated effects on hemostasis, including blood clotting and fibrinolysis.
    • Investigate the contributions of additional risk factors for AD, including diabetes, lipid metabolism, hypertension, diet, exercise, head injury, and aging, on cerebrovascular function.
    • Develop models of small vessel disease and a platform of informative outcome measures to understand how small vessel disease contributes to both white and grey matter lesions, neurodegeneration, and cognitive function.
    • Determine additive or synergistic effects among risk factors.
    • Strategically mine GWAS studies and clinical trials focused on vascular applications for additional pathways and targets that further increase the translatability of animal model studies.
    • Small vessel disease animal models can be used to study the influence of AD genetic risk factors such as APOE.

Recommendation 3. Encourage basic science research that investigates the impact of cerebrovascular risk factors on AD-related neurodegeneration (3-7 y).

  • The high co-morbidity of cerebrovascular disease with AD necessitates the study of these two processes together.

  • Studies should be encouraged that will examine common cerebrovascular disease risk factors in AD animal models. These studies should cover both Aβ- and tau-related disease processes, both separately and together.

  • The development of animal models should move beyond stroke models and into more chronic models of cerebrovascular disease that are commonly co-morbid with AD. Models of cerebrovascular disease should, when possible, distinguish between white matter and gray matter damage and determine how each type contributes to AD progression.

  • Pursue studies to understand shared cellular and molecular mechanisms within the small vessel neurovascular unit leading to secondary neurodegeneration in Aβ- independent and tau-independent pathways, and within the Aβ pathway and the tau pathway (e.g., receptor for advanced glycation end products (RAGE), lipoprotein receptors, endothelial and pericyte cell-specific gene deletion and expression).

  • Cognitive and behavioral tests should, when modeling VCI/VaD, include functional testing of brain regions impacted by cerebrovascular disease.

Focus Area 2 - Human-Based Studies

Recommendation 1. Develop (1-3 y) and validate (3-7 y) noninvasive markers of key vascular processes related to cognitive and neurologic impairment.

  • Identify biomarkers of key microvascular processes related to cognitive and neurologic impairment, including biomarkers of tissue injury (e.g., microinfarcts, ischemic white matter damage); vessel disease (e.g., cerebral amyloid angiopathy, arteriosclerosis); and other vascular alterations such as blood brain barrier dysfunction, vascular reactivity, and hypoperfusion. Modalities may include but are not limited to neuroimaging, systemic (blood/urine) and central nervous system (CNS) fluids.

  • Pursue cross-directional interdisciplinary studies to validate and explore the links between vascular biomarkers and the key microvascular processes.

  • Incorporate the above pathologically validated vascular biomarkers in clinical studies to determine their association with risk factors and cognitive/neurologic impairment and decline in human subjects.

Recommendation 2. Determine interrelationships among cerebrovascular disease and risk factors, Aβ, and neurodegeneration (3-7 y).

  • Characterize the interrelationships among vascular risk factors, cerebrovascular disease, and AD in order to identify and target specific vascular risk factors to reduce the risk of AD, VCI, and multiple etiology dementia.

  • Determine relationships of vascular risk factors and AD biomarkers to biomarkers of cerebrovascular disease, such as endothelial cell function, blood brain barrier permeability, vascular stiffness, and other measures of vascular physiology.

  • Encourage studies that address the complex pathways leading from vascular risk factors and cerebrovascular disease to changes in cognition, brain structure, Aβ, tauopathy, and neurodegeneration. Such studies may include systems-based approaches incorporating multi-modal imaging, biochemical, genetic and clinical markers to help determine whether risk conditions common to both AD and cerebrovascular disease reflect convergent pathways versus additive effects of independent pathways.

  • Investigate correlation of systemic vs. CNS biomarkers. Vascular risk factors are often measured systemically and we have limited knowledge about how they correspond with CNS metabolism.

  • Encourage studies of how diet, exercise, lifestyle, and systemic vascular risk factors affect Aβ, tauopathy, metabolism, inflammation, and oxidative stress.

Recommendation 3. Identify next generation vascular interventions to treat or prevent VCI and VaD (7-10 y).

  • Establish clinical trials to develop surrogate markers for severity of VCI and VaD. Such trials could be those relating the burden of VCI to imaging markers such as the frequency or distribution of lacunar strokes, neurophysiological markers such as cerebrovascular reserve or functional imaging, or molecular biomarkers obtainable from the subjects such as genetic or proteomic measures.

  • Currently, there are no known interventions that are specifically geared to VCI and VaD. However, there are several interventions that are known to impact general vascular risk factors, including management of hypertension, statins, control of diabetes, diet, exercise, and other lifestyle interventions. In particular, if we are successful in developing clinical or surrogate markers for diagnosing and quantifying VCI and VaD with some specificity, it would be relevant to determine whether or not and to what degree existing vascular interventions may beneficially impact VCI burden. By necessity, these would have to be long-term, longitudinal cohort studies.

  • Develop clinical trials using outcome markers developed in parallel with animal models. This will allow direct ties to be drawn between the results of animal- and human-based interventions. Human-based clinical trials also should seek to develop and validate standardized cognitive test batteries for VCI as a potential step towards improving clinical diagnosis and measurement of clinically meaningful trial outcomes.

Memorandum from the NINDS Director Dr. Story Landis

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National Institutes of Health
National Institute of Neurological
Disorders and Stroke

Office of the Director
Building 31, Room 8A52
31 Center Drive MSC 2540
Bethesda, Maryland 20892-2540
Office: (301) 496-9746
Fax: (301) 496-0296

DATE: September 23, 2013

TO: NAPA Council

FROM: Director, NINDS

SUBJECT: Alzheimer's Disease-Related Dementias (ADRD) Conference Recommendations to the NINDS Council

The Chair of the recent Alzheimer's Disease-Related Dementias (ADRD) Conference presented the recommendations of that meeting to the NINDS Council, which is a FACA committee. The NINDS Council discussed and approved the ADRD Conference 2013 Report on September 12, 2013. The recommendations emerged from a year-long iterative process involving more than 80 national and international expert scientists, including a steering committee with 2 NINDS Council members (David Holtzman, Sharon Hesterlee), the Chair of the NAPA Council (Ron Petersen), and representation from the NIA (Neil Buckholtz). Additional input from scientists as well as the public, including patients and their advocate, was provided at the Conference.

NINDS Council members recognized that the ADRD 2013 Report represents a consensus document and that setting priorities is very difficult, given the lack of understanding of the underlying mechanisms responsible for these diseases and the lack of treatments. Nonetheless, during discussion that resulted in approval, several NINDS Council members considered the Lewy body dementia (LBD) and frontotemporal dementia (FTD) sections of the Report, and provided comments that are summarized as follows:

  1. Biomarker and mechanistic discoveries for synucleinopathy, tauopathy, TDP-43opathy, etc., are critically important for FTD and LBD, as they are for vascular contributions to dementia, since advances in these areas are necessary to inform the design of cohort studies and clinical trials.

  2. For FTD, efforts designed to increase understanding of the mechanisms underlying TDP- 43opathy, FUS and C9orl72-related neurodegeneration are as important as efforts to increase understanding of mechanisms underlying tauopathy.

The signature of Story C. Landis, Ph. D.
Story C. Landis

Abbreviated Agenda

Links & Resources

May 1, 2013

7:00 a.m.
8:00 a.m.
Story Landis, PhD, NINDS, Director
Ron Petersen, MD, PhD, Mayo Clinic
Thomas Montine, MD, PhD, University of Washington
8:30 a.m.
Session 1: Alzheimer's Disease Related Dementias (ADRD) and Multiple Etiology Dementias: the Public Health Problem and Improving Recognition across the Spectrum
Session Chairs:
Bruce Miller, MD, University of California, San Francisco
David Knopman, MD, Mayo Clinic
9:30 a.m.
Session 2: Lewy Body Dementias
Session Chairs:
Dennis Dickson, MD, Mayo Clinic
Karen Marder, MD, MPH, Columbia University
12:15 p.m.
1:15 p.m.
Session 3: Frontotemporal Dementia (FTD) and AD-Related Tauopathies
Session Chairs:
Michael Hutton, PhD, Eli Lilly
William Seeley, MD, University of California, San Francisco
5:00 p.m.
End of day 1

May 2, 2013

7:30 a.m.
8:30 a.m.
Session 4: Vascular Contributions to ADRD
Session Chairs:
Steven Greenberg, MD, PhD, Harvard University
Berislav Zlokovic, MD, PhD, University of Southern California
11:30 a.m.
12:30 p.m.
Session 5: Health Disparities in ADRD
Session Chairs:
Jennifer Manly, PhD, Columbia University
Maria Glymour, ScD, Harvard University
3:15 p.m.
Open Discussion and Concluding Remarks
4:00 p.m.
End of day 2


Scientific Workshop Chair

Thomas Montine MD, PhD is an expert on the structural and molecular bases of cognitive impairment that occur with advancing age, and how these processes merge with Alzheimer's disease and Parkinson's disease. The goal is to define key pathogenic steps through fundamental and clinical research, and thereby identify new potential therapeutic targets to protect cognitive function. Dr. Montine's laboratory addresses these prevalent medical problems through a combination of epidemiology-neuropathology, genomics-neuropathology, biomarkers for clinical investigation and clinical trials, and experimental studies that test hypotheses concerning neuroprotection from free radical injury and innate immune activation in specific regions of the brain.

NIH Lead

Roderick Corriveau, PhD is the NINDS Program Director overseeing research on Alzheimer's disease, vascular dementias, and CADASIL. For Alzheimer's disease research, his portfolio is focused on molecular mechanisms of disease pathophysiology with areas of emphasis including but not limited to: (1) APP, beta-amyloid, presenilins, tau, neurotrophins and synaptic proteins; (2) animal models; (3) neuroinflammation; (4) post-translational protein modifications; and (5) protein trafficking and clearance.

Chair of the Advisory Council on Alzheimer's Research, Care, and Services

Ronald C. Petersen, MD, PhD is Professor of Neurology, the Cora Kanow Professor in Alzheimer's Disease Research, and a Mayo Clinic Distinguished Investigator. He is on the National Advisory Council on Aging, and is the chair of the Advisory Council on Research, Care and Services for the National Alzheimer's Project Act appointed by the Secretary of the Department of Health and Human Services. Dr. Petersen is a recipient of the 2004 MetLife Foundation Award for Medical Research in Alzheimer's Disease, and the 2005 Potamkin Prize for Research in Pick's, Alzheimer's and Related Disorders.

Session Chairs

Dennis W. Dickson, MD concentrates his research on the neuropathologic characterization of brains from prospective and longitudinal research studies sponsored by the National Institute on Aging. Brains come from the Mayo Clinic Alzheimer's Disease Research Center, the Mayo Clinic Study of Aging, and the Einstein Aging Study at Albert Einstein College of Medicine. Dr. Dickson's research areas include genetic studies, non-Alzheimer's degenerative diseases, disorders in tau pathology, and ALS and frontotemporal degeneration with TDP-43 pathology. These studies aim to understand the molecular pathology of neurodegenerative disorders that will lead to better diagnosis, treatment and eventually prevention of these devastating disorders. Dr. Dickson's professional highlights include the 2011 Potamkin Prize for Research in Pick's, Alzheimer's and Related Diseases, American Academy of Neurology; MetLife Foundation 2001 Award for Medical Research; and Past President, American Association of Neuropathologists.

Maria Glymour, ScD is an associate professor at the University of California, San Francisco. She is a social epidemiologist trained at the Harvard School of Public Health and Columbia University Mailman School of Public Health. Her research focuses on social inequalities in old age health, including cognitive function, dementia, and stroke. She is interested in overcoming such methodological problems encountered in neuroepidemiology and social epidemiology as statistical biases in common longitudinal analyses, selective attrition in dementia studies, and accounting for time-varying confounding to identify causal determinants of dementia and cognitive losses. She currently focuses on longitudinal trajectories of functioning and determinants of resilience in the context of stroke and dementia; genetic instrumental variables analyses to assess the intersection of vascular disease and cognitive outcomes; and lifecourse social determinants of stroke and cognitive aging.

Steven Greenberg, MD, PhD is Professor of Neurology at Harvard Medical School. He holds the John J. Conway Endowed Chair in Neurology, and is Director of the Hemorrhagic Stroke Research Program at the Massachusetts General Hospital (MGH). Initiated in 1994, the Hemorrhagic Stroke Research Program has become internationally recognized as a leading authority on the causes, diagnosis, and treatment of cerebral amyloid angiopathy. Dr. Greenberg has authored over 190 research articles, chapters, reviews, and editorials in the areas of hemorrhagic stroke and small vessel brain disease. He has served as principal investigator on multiple national research grants, and in leadership positions at national and international conferences on hemorrhagic stroke and vascular cognitive impairment. He currently serves as Chair of the American Heart Association International Stroke Conference Program Committee and Director of Faculty Development and Promotions for the MGH Department of Neurology. Dr. Greenberg received his undergraduate degree in Biochemistry from Harvard University and MD and PhD degrees from Columbia University.

Michael Hutton, PhD is the Chief Scientific Officer for Neurodegenerative Disease at Eli Lilly, a position he has held since joining the company in 2009. He was appointed UK Site Scientific Leader in 2012 and leads drug discovery for Alzheimer's disease, Parkinson's disease, and frontotemporal dementia. Eli Lilly's Alzheimer's program has delivered multiple drug candidates to clinical development, including an anti-amyloid antibody (solanezumab) that was recently reported to slow cognitive decline in mild AD in Phase 3 and a BACE1 inhibitor. Prior to joining Lilly, Dr. Hutton worked at Merck and at the Mayo Clinic Jacksonville. During his time at Mayo, his team played a major role in determining the causes of frontotemporal dementia with the discovery of mutations in tau and progranulin and the mechanism by which these lead to neurodegeneration. He was awarded the Potamkin Prize and MetLife Foundation Award in 2000 and 2001, respectively for his work on frontotemporal dementia.

David Knopman, MD is a 1972 graduate of Dartmouth College, a 1973 graduate of Dartmouth Medical School, and a 1975 graduate of the University of Minnesota Medical School. He did his internship at Hennepin County Medical Center, Minneapolis, a neurology residency at the University of Minnesota, and a fellowship in Behavioral Neurology at Hennepin County Medical Center and the University of Minnesota. He was a faculty member at the University of Minnesota from 1980 to 2000. He joined the Department of Neurology at the Mayo Clinic Rochester, MN in 2000, where he is currently Professor of Neurology, Mayo Clinic College of Medicine. He also is a Consultant in Neurology at the Mayo Clinic, and a co-investigator in the Mayo Alzheimer's Disease Research Center. His research and clinical interests have been in dementing illnesses. He is an author on more than 350 research articles on various topics in dementia, including aspects of vascular dementia, frontotemporal dementia,and Alzheimer's. disease. Dr. Knopman is Deputy Editor of Neurology and was the senior author on the 2001 AAN Practice Parameter on the Diagnosis of Dementia. He co-chaired the NIA-AA committee that drafted the revised criteria for Alzheimer's disease dementia. In 2012, he became a member of the Medical and Scientific Advisory Council of the Alzheimer's Association.

Jennifer Manly, PhD is an Associate Professor of Neuropsychology and Neurology at the G.H. Sergievsky Center and the Taub Institute for Research in Aging and Alzheimer's disease at Columbia University. She completed her graduate training in neuropsychology at the San Diego State University/University of California at San Diego Joint Doctoral Program in Clinical Psychology. After a clinical internship at Brown University, she completed a postdoctoral fellowship at Columbia University. Her research on cognitive and genetic aspects of aging and Alzheimer's disease among African Americans and Hispanics has been funded by the National Institute on Aging and the Alzheimer's Association. She has authored over 90 peer-reviewed publications and eight chapters. She is an associate editor of the Journal of the International Neuropsychological Society. She was recently selected to serve on the US Department of Health and Human Services Advisory Council on Alzheimer's Research, Care and Services, and joined the Alzheimer's Association Medical & Scientific Research Board in 2012.

Karen S. Marder, MD, MPH is the Sally Kerlin Professor of Neurology at Columbia University Medical Center. She has served as the Chief of the Division of Aging and Dementia since 1991 and has directed the United Council for Neurologic Subspecialties fellowship in Behavioral Neurology and Neuropsychiatry since its inception. Her research and clinical care have focused on the epidemiology and treatment of cognitive, behavioral and motor impairments in a range of neurodegenerative diseases, including Parkinson's disease (PD), Huntington's disease, HIV dementia, and Alzheimer's disease and related disorders. Since 1998 she has focused on characterizing the earliest motor and non-motor signs associated with genetic forms of PD. She served as Co-Chair and then Chair of the executive committee of the Parkinson's Study Group (2006-2012), a consortium of North American investigators at 120 sites who participate in collaborative PD research. She is Associate Director of the Irving Institute for Clinical and Translational research (CTSA) and Co-PI of the Columbia-Weill Cornell NeuroNEXT site, whose goal is to conduct five to seven Phase II biomarker informed neurological clinical trials over a 7- year period.

Bruce Miller, MD is Professor of Neurology at the University of California, San Francisco (UCSF) where he holds the A.W. & Mary Margaret Clausen Distinguished Chair. He also directs the UCSF dementia center, with a goal of delivering model care to all patients who enter the clinical and research programs at the MAC. Dr. Miller is a behavioral neurologist focused in dementia with special interests in brain and behavior relationships, as well as the genetic and molecular underpinnings of disease. His work in frontotemporal dementia (FTD) emphasizes both the behavioral and emotional deficits that characterize these patients, while simultaneously noting the visual creativity that can emerge in the setting of FTD. He is the principal investigator of the NIH- sponsored Alzheimer's Disease Research Center and an NIH-funded program project called Frontotemporal Dementia: Genes, Imaging and Emotions. He helps lead two philanthropy-funded research consortia, the Tau Consortium and Consortium for Frontotemporal Research, focused around developing treatments for tau and progranulin disorders respectively. For nearly three decades, Dr. Miller has been the scientific director for the philanthropic organization The John Douglas French Alzheimer's Foundation. He has worked with the National Football League to help with player education and assessment related to brain health. Dr. Miller has received many awards, including the Potamkin Award, the Raymond Adams Lecture at the American Neurological Association, the UCSF Academic Senate Distinction in Mentoring Award, and the Gene D. Cohen Research Award in Creativity and Aging from the National Center for Creative Aging. He has authored The Human Frontal Lobe, The Behavioral Neurology of Dementia and extensive publications regarding dementia.

William Seeley, MD graduated from Brown University in 1994 with a degree in Psychology. He attended medical school at the University of California, San Francisco (UCSF), where he first encountered patients with frontotemporal dementia—which became his primary research focus. He completed a neurology residency at Harvard Medical School and training at the Massachusetts General and Brigham & Women's Hospitals, before returning to UCSF for a Behavioral Neurology fellowship with Bruce Miller. Dr. Seeley's clinical practice focuses on patients with neurodegenerative disease, especially those suffering from dementia. His research goals are to clarify mechanisms of selective vulnerability by blending anatomy, neuroimaging, and pathology with molecular-genetic analyses; and accelerate drug discovery by developing network-based neuroimaging biomarkers for monitoring disease progression. His work was recognized in 2011 with a MacArthur Foundation Fellowship. He is currently Associate Professor of Neurology at UCSF and Director of the UCSF Neurodegenerative Disease Brain Bank.

Berislav Zlokovic, MD, PhD is Director of the Zilkha Neurogenetic Institute and Professor and Chair of the Department of Physiology and Biophysics at the University of Southern California, Keck School of Medicine, Los Angeles. Dr. Zlokovic has a long-standing interest in understanding the role of cerebral blood vessels, CNS microcirculation and blood-brain barrier (BBB) in pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD) and ALS, and ischemic brain injury as foundations for development of new therapies for AD, related neurodegenerative disorders and stroke. Using animal models and studying human brain, his laboratory has convincingly demonstrated that damage to the BBB and brain microcirculation can accumulate before neuronal dysfunction and injury. His research team has identified the cellular and molecular mechanisms in cerebral blood vessels and neurovascular unit causing BBB disruption which leads to neuronal dysfunction and degenerative changes in models of AD, ALS, pericyte-deficient rodents and stroke. Discoveries of his research team have contributed to the development of clinical trials based on amyloid-beta clearance in AD patients, and a new therapeutic approach for stroke based on activated protein C mutant that is currently under clinical assessment as a neuroprotective agent.


Dag Aarsland, MD, PhD is Professor of Clinical Dementia Research at the Alzheimer's Disease Research Centre at Karolinska Institute in Stockholm, Sweden and Research Director at Centre for Age-Related Medicine, Stavanger University Hospital in Stavanger, Norway. He is a psychiatrist and has worked as a senior consultant in geriatric psychiatry for most of his career. His main research interest is the neuropsychiatric aspects of patients with neurodegenerative diseases, in particular translational studies on cognitive decline in Parkinson's disease.

Karen Ashe, MD, PhD has been a University of Minnesota faculty member since 1992. She received her A.B. from Harvard University in 1975, her PhD from the Massachusetts Institute of Technology in 1981, and her MD from Harvard University in 1982. She holds the Edmund Wallace and Anne Marie Tulloch Chairs in Neurology and Neuroscience, and directs the N. Bud Grossman Center for Memory Research and Care. Her contributions to the genetics of human prion diseases resolved the paradox of how prion diseases could be both infectious and inherited. Her transgenic mouse models of prion and Alzheimer's diseases have been useful for validating genetic linkage studies, for understanding disease pathogenesis, for seeking markers of early disease processes, and for testing candidate therapies. The Tg2576 model of pre-clinical Alzheimer's disease she developed and distributed freely around the world has been used to discover a pathogenic amyloid- beta oligomer that may initiate Alzheimer's disease. Her rTg4510 mouse was used to show that neurofibrillary tangles do not cause memory deficits, disproving a century-old idea. Dr. Ashe has received numerous awards and honors, including the MetLife Award in 2005, the Potamkin Prize in 2006, and induction into the Institute of Medicine in 2009.

Lisa Barnes, PhD is Professor in the departments of Neurological Sciences and Behavioral Sciences and Director of the Rush Center of Excellence on Disparities in HIV and Aging at Rush University Medical Center. She received her PhD in biopsychology from the University of Michigan and subsequently completed a postdoctoral fellowship at UC Davis Center for Neuroscience. Her research has focused on risk factors for cognitive decline and Alzheimer's disease in African Americans. She has expertise designing, conducting, and analyzing longitudinal studies of racial disparities, aging, and Alzheimer's disease, including clinical-pathologic studies. She is Principal Investigator of the NIA-funded Minority Aging Research Study, a longitudinal epidemiologic study of over 500 older African Americans designed to examine the neuropathologic basis of cognitive impairment. She is the Co-Leader for the Clinical Core of the Rush Alzheimer's Disease Core Center. She has published extensively on racial disparities in aging-related conditions. Dr. Barnes is a Fellow of the Leadership Institute for Women in Psychology of APA and the Institute of Medicine of Chicago.

David Bennett, MD is the Robert C. Borwell Professor of Neurological Sciences and director of the Rush Alzheimer's Disease Center. Dr. Bennett received a bachelors degree in physiology from the University of Michigan, Ann Arbor, in 1979. He earned his doctorate in medicine from Rush Medical College in Chicago, IL in 1984. Following his medical internship, Dr. Bennett returned to Rush for residency training in neurology and a research fellowship in dementia. He is internationally known for his research regarding the causes, treatment, and prevention of Alzheimer's disease and other common neurologic conditions of aging. Dr. Bennett's primary research interest is understanding the neurobiologic pathways linking genetic and environmental risk factors to loss of cognition, and understanding why many older persons are able to live with severe Alzheimer's disease changes in the brain without suffering from memory loss (cognitive or neural reserve). He is principal investigator of several studies funded by the National Institute on Aging, including the Rush Alzheimer's Disease Core Center, the Religious Orders Study, and Rush Memory and Aging Project. He also directs the Regional Alzheimer's Disease Assistance Center for Northern Illinois. He serves on numerous state, national, and international advisory and editorial boards, and has more than 300 manuscript publications.

Geert Jan Biessels, MD, PhD is a professor of neurology at the University Medical Centre Utrecht, the Netherlands, with a chair on cerebrovascular disease and cognition. He obtained his PhD in 1997 and was certified as a neurologist in 2004. His research at the Department of Neurology of the Rudolf Magnus Institute for Neuroscience focuses on the role of vascular disease in cognitive decline and dementia, particularly in people with diabetes. His group has studied the severity and course of development of cognitive decrements in diabetes and pre-diabetic stages, the relation with vascular disease, and identified brain MRI correlates of impaired cognition. Dr. Biessels is also interested in the development and application of novel imaging markers of vascular cognitive impairment. In this context, high-resolution 7T MRI of cerebral small vessel disease appears to be a very promising technique and recently his group has shown that it is possible to depict cortical microinfarcts in vivo. He is an author of over 140 papers on the impact of diabetes and other vascular risk factors on the brain and novel imaging markers of small vessel disease.

Brad Boeve, MD is a neurologist with subspecialty training in behavioral/cognitive neurology and sleep medicine. Over the past 15 years he has been focused on the clinical, sleep, neuropsychological, genetic, neuroimaging, and neuropathologic aspects of the neurodegenerative disorders which manifest as cognitive impairment and/or parkinsonism. These disorders include mild cognitive impairment and/or mild parkinsonian signs, dementia with Lewy bodies/Parkinson's disease with dementia, the frontotemporal lobar degeneration (FTLD)- spectrum disorders, and the rapidly progressive dementias such as Creutzfeldt-Jakob disease and the autoimmune/inflammatory encephalopathies. The prodromal features of evolving Lewy body disease (namely REM sleep behavior disorder) and presymptomatic and early symptomatic phases of the genetically-mediated FTLD-spectrum disorders are particular interests. He has worked with many colleagues in the Mayo Alzheimer's Disease Research Center, Mayo Clinic Study of Aging, Mayo Center for Sleep Medicine, and Morris K. Udall Center of Excellence for PD Research at Mayo Clinic, as well as multiple colleagues at other academic institutions, to advance knowledge in the Alzheimer's disease-related dementias.

Adam Boxer, MD, PhD is an Associate Professor of Neurology at the University of California, San Francisco (UCSF) where he directs the Neurosciences Clinical Research Unit in the new Sandler Neurosciences Center. He also directs the Alzheimer's Disease and Frontotemporal Lobar Degeneration (FTLD) Clinical Trials Program at the UCSF Memory and Aging Center. Dr. Boxer's research is focused on developing new treatments and biomarkers for neurodegenerative diseases, particularly those involving the pathogenic proteins, tau and TDP-43. He is the principal investigator of the Four Repeat Tauopathy Neuroimaging Initiative (4RTNI), a multicenter, longitudinal biomarker study modeled after the Alzheimer's Disease Neuroimaging Initiative (ADNI), that is focused on progressive supranuclear palsy (PSP) and corticobasal degeneration, and funded by the NIH and a private foundation, the Tau Consortium. He was the principal investigator for two recently-completed, multicenter, randomized, placebo controlled clinical trials of memantine for FTLD and davunetide for PSP. He leads the FTLD Treatment Study Group, an academic-industry collaborative group working to speed the development of new therapies for FTLD. He is a recipient of the 2013 Part the Cloud Award for Translational Research from the Alzheimer's Association.

Monique Breteler, MD, PhD studies the etiology and preclinical detection of neurodegenerative, neuropsychiatric, and cerebrovascular diseases. For more than 20 years she worked at the Department of Epidemiology at Erasmus University Rotterdam, the Netherlands, which she joined to develop the neurologic component in the Rotterdam Study, a large prospective cohort study on chronic diseases in the elderly. Until 2011, she was the primary investigator for neurological diseases of the Rotterdam Study and initiated the Rotterdam Scan Study, both internationally leading population studies in the area of neurodegenerative diseases. In 2011 she accepted the position of director of Population Health Sciences of the newly founded German Center for Neurologic Diseases, as well as a professorship in Population Health Sciences at the University Bonn, Germany. In Bonn she is establishing the Rhineland Study, a prospective cohort study of 30,000 individuals that aims to identify causes and preclinical multimodal biomarker profiles of neurodegenerative and neuropsychiatric diseases, and to investigate normal and pathological brain structure and function over the adult life course.

Nigel Cairns, PhD is interested in clarifying the pathological changes in the brains of patients with frontotemporal diseases and the mechanisms by which nerve cells die and cause dementia. His multidisciplinary approach uses histological, biochemical, and cell biological methods, and a mouse model of dementia to determine the role of candidate pathological proteins in frontotemporal diseases. These experiments may throw new light on the pathogenesis of this enigmatic group of diseases and generate novel avenues for therapeutic intervention. A native of the United Kingdom, Nigel Cairns received his BA from London University and BSc from the University of Bristol. He obtained a PhD in 1995 in experimental neuropathology while working on the pathogenesis of Alzheimer's disease at the Institute of Psychiatry, King's College, University of London. In 1998, he became a member of the Royal College of Pathologists of the United Kingdom. In 2002, the American Association of Neuropathologists presented him with the Moore Award. Between 2003 and 2004, he worked at the Center for Neurodegenerative Disease Research, University of Pennsylvania. Dr. Cairns joined the Washington University School of Medicine in 2004 as Research Associate Professor, and in 2012 he was appointed Research Professor in the Departments of Neurology and Pathology & Immunology. He is the Core Leader of the Neuropathology Core of the Knight Alzheimer's Disease Research Center, the multicenter Alzheimer's Disease Neuroimaging Initiative (ADNI), and the international Dominantly Inherited Alzheimer's Network. He leads the Betty Martz Laboratory for Neurodegenerative Research.

Cynthia Carlsson, MD is a board-certified internist and geriatrician with clinical and research expertise in geriatrics, dementia, vascular biology, biomarkers, and clinical trials. Since 2003 she has served as the Medical Director of the multidisciplinary Madison VA Memory Assessment Clinic - a clinic which serves Veterans with memory disorders from throughout Wisconsin, Michigan, and Illinois. As part of a nationwide movement to improve clinical dementia care of Veterans, Dr. Carlsson served as Co-Chair of the VA National Dementia Clinical Care Treatment Subcommittee in 2007 and continues to serve locally on the Madison VA Dementia Committee to implement these national recommendations. Her research interest focuses on the relationship of vascular risk factors and their treatment to the development of dementia, integrating use of cerebrospinal fluid, neuroimaging, and cognitive biomarkers. As part of the NIA Women's Health & Aging: Clinical Scientist Development Award and an NIA Beeson Career Development Award, she received additional research training in clinical trial methodology, population health sciences, epidemiology, and biostatistics. She has served as the Principal Investigator on NIH-funded trials investigating the role of vascular risk modification in the development of Alzheimer's disease, and has also received research funding from the University of Wisconsin (UW) General Clinical Research Center, the American Federation for Aging Research, the UW Department of Medicine, and the Wisconsin Comprehensive Memory Program. As Clinical Core Co-Leader for the Wisconsin Alzheimer's Disease Research Center (ADRC), Dr. Carlsson oversees the recruitment and evaluation of participants into the Center and leads the ADRC's CSF Collection Service.

Helena Chui, MD is internationally recognized for her research in Alzheimer's disease and vascular cognitive impairment. She is the principal investigator for the NIA-funded Alzheimer Disease Research Center, as well as multi-institutional program projects on vascular dementia. Dr. Chui is the author of over 157 publications and has served on the editorial board for Stroke, Alzheimer Disease and Associated Disorders, and Archives of Neurology. At the University of Southern California, she holds the Raymond and Betty McCarron endowed Chair at the Keck School of Medicine and serves as the Chair of the Department of Neurology.

Thomas Cooper, MD did his postdoctoral training at the University of California, San Francisco and joined the faculty of Baylor College of Medicine in 1989. Since 2003 he has held the S. Donald Greenberg Endowed Chair of Pathology. The work from Dr. Cooper's lab helped identify the RNA gain of function mechanism responsible for pathogenesis of myotonic dystrophy. His laboratory currently investigates the pathogenic mechanisms of the RNA gain of function, and is also at the forefront in deciphering the role of alternative splicing in postnatal development using high throughput approaches. Dr. Cooper has served on peer review committees for the National Institutes of Health, the American Heart Association, and the Muscular Dystrophy Association, and is on the scientific advisory board of the Packard Foundation for ALS research at Johns Hopkins University School of Medicine.

Suzanne Craft, PhD received her degree specializing in Neuropsychology from the University of Texas at Austin, and then completed fellowships in Behavioral Neuroscience at Boston University and Harvard Medical School. She is Professor of Medicine at Wake Forest School of Medicine. Her research investigates the mechanisms through which peripheral and brain insulin resistance contributes to the development of Alzheimer's disease. Based on this work, her laboratory has now begun trials of intranasal insulin, exercise, and dietary intervention as possible therapeutic or preventative approaches for Alzheimer's disease. She is a recipient of an NIH MERIT award, an Alzheimer's Association Zenith Award, and a special grant from the National Alzheimer's Plan to carry out a multisite study of intranasal insulin for the treatment of early AD.

Marc Diamond, MD is recognized for his research to develop therapeutics and diagnostic tests for tauopathies. He was the first to describe fundamental cellular mechanisms of cell-cell propagation of tau protein pathology. His research now addresses the basic cellular mechanisms by which tau aggregates bind the cell surface, and their mechanism of uptake and intracellular seeding. Dr. Diamond's lab has used cellular assays that detect seeding activity in tauopathy brain lysate to identify therapeutic antibodies, one of which has been thoroughly tested in a mouse model, and has been licensed for humanization and testing in people. He has additionally developed cell-based assays that sensitively detect tau seeding activity in biological samples, and which we are developing as "biosensors" of incipient pathology in patients. In collaboration with the laboratory of David Holtzman, Dr. Diamond's lab members are continuing their efforts to develop next generation therapeutic and diagnostic antibodies for tauopathy.

Karen Duff, PhD holds appointments in the Departments of Pathology and Cell Biology, Psychiatry and the Taub institute. In the last 20 years, Dr. Duff has genetically engineered several widely used mouse models for AD, tauopathies and synucleinopathies. These mice have been used in studies ranging from MRI and PET for diagnostics development, to proof-of-concept testing of therapeutic targets. Currently, her main interests are in studying how Alzheimer's disease-related pathology and dysfunction propagates though the brain as the disease worsens, the role of aging and inheritance of the AD risk variant APOE4 as initiating factors in AD, and the role and therapeutic potential of protein clearance pathways in tauopathies. Dr. Duff received her PhD from Sydney Brenner's department at the University of Cambridge (UK) in 1991, then moved to the US and took positions at the University of South Florida, Mayo Clinic Florida, and the Nathan Kline Institute/New York University. She has received several awards, among them the Potamkin Prize in 2006.

David Eidelberg, MD is Director of the Center for Neurosciences and the NIH Morris K. Udall Center of Excellence for Parkinson's Disease Research at the Feinstein Institute for Medical Research in Manhasset, New York. Dr. Eidelberg is internationally recognized for his pioneering work using functional imaging to identify abnormal functional brain networks in neurological disorders. Dr. Eidelberg's work has led to the development of novel image-based methods for the assessment of disease progression, treatment response, and to enhance the accuracy of clinical diagnosis. He received his MD from Harvard Medical School. After completing residency training in neurology at the Harvard-Longwood Area Training Program, he pursued postdoctoral training as a Moseley Traveling Fellow at the National Hospital, Queen Square in London and at Sloan-Kettering Institute in New York. Dr. Eidelberg moved to North Shore University Hospital in Manhasset, NY in 1988 to establish the functional imaging laboratory and the clinical movement disorders program. In 2001 he became the founding director of the Center for Neurosciences at The Feinstein Institute for Medical Research, where he is currently Susan and Leonard Feinstein Professor of Neurology and Neuroscience. Dr. Eidelberg has received many grants and awards, including the Fred Springer Award (2005) and the American Academy of Neurology Movement Disorders Research Award (2010). He is author of over 350 peer-reviewed scientific articles and reviews and serves on the editorial boards of The Journal of Neuroscience, Annals of Neurology, NeuroImage, and the Journal of Nuclear Medicine. Dr. Eidelberg currently serves on the scientific advisory board of The Michael J. Fox Foundation.

Howard Feldman, MD, FRCP (C) is Professor of Neurology and Executive Associate Dean, Research at the Faculty of Medicine, University of British Columbia, Vancouver. In his research, Dr. Feldman has made seminal contributions to his field with scientific discoveries and clinical research focused on aging, mild cognitive impairment/Alzheimer's disease, frontotemporal dementia (FTD) and diagnostic/therapeutic trials. His research group contributed to the discoveries of the progranulin (Nature 2006) and C9ORF72 (Neuron 2011) genetic mutations which cause FTD and FTD with motor neuron disease as well as to the development of important novel criteria for Alzheimer's disease. His career contributions have been profiled in Lancet Neurology in 2007, and he has been appointed as Fellow of the Canadian Academy of Health Sciences and of the American Academy of Neurology. He has served as inaugural Fisher Family and Alzheimer Society of British Columbia Endowed Professorship for Research in Alzheimer's Disease. From 2009-2011, he took a leave from his academic appointment in Vancouver to take on a senior leadership role in neuroscience global clinical research at Bristol-Myers Squibb, where his research focused on developing novel pharmaceutical therapies for neurodegenerative and other neurological/psychiatric disorders.

James E. Galvin, MD, MPH is Professor of Neurology, Psychiatry, Nursing, Nutrition and Population Health at New York University Langone School of Medicine. He serves as Director of the Pearl I. Barlow Center for Memory Evaluation and Treatment; Lewy Body Dementia Program; NYU Alzheimer Disease Assistance Center; and as Associate Director of the NIA-funded Alzheimer's Disease Center. He has authored over 115 scientific publications in the area of neurodegenerative disorders, dementia and cognitive aging, and leads numerous clinical trials. Dr. Galvin's research has been funded by the National Institutes of Health, Michael J Fox Foundation, American Federation for Aging Research, Alzheimer's Association, New York State Department of Health and the Morris and Alma Schapiro Fund.

Michael Geschwind, MD, PhD is an Associate Professor of Neurology and holds the Michael J. Homer Chair in Neurology at the University of California, San Francisco (UCSF), Memory and Aging Center. Dr. Geschwind received his MD and PhD in neuroscience through the National Institutes of Health-sponsored Medical Scientist Training Program at the Albert Einstein College of Medicine in New York. He completed his internship in internal medicine at the University of California, Los Angeles Medical Center, his neurology residency at the Johns Hopkins University School of Medicine in Baltimore, and his fellowship in behavioral neurology at the UCSF Memory and Aging Center. He joined the Memory and Aging Center faculty in 2003. Dr. Geschwind's primary research interest is the assessment and treatment of rapidly progressive dementias, including prion diseases such as Creutzfeldt-Jakob disease, autoimmune antibody-mediated dementias, and encephalopathies. He also has an active interest in movement disorders and cognition, including progressive supranucelar palsy (PSP), corticobasal syndrome (CBS), and Huntington's disease (HD). He is an active member of the Huntington's Study Group. In 2011 Dr. Geschwind became a member of the Clinical Research Consortium for Spinocerebellar Ataxia – a group of international investigators interested in the research, treatment, and cure of genetic ataxias. Dr. Geschwind evaluated patients with assorted dementias, including Alzheimer's disease, frontotemporal dementia (FTD)-spectrum disorders (including PSP and CBS), HD, leukoencephalopathies (including CADASIL), and other disorders. He recently opened a new clinic for antibody-mediated autoimmune encephalopathy and related disorders.

Alison Goate, PhD is the Samuel & Mae S. Ludwig Professor of Genetics in Psychiatry and Professor of Genetics and Professor of Neurology at Washington University's School of Medicine in St. Louis. She is also Director of the Hope Center for Neurological Disorders and Associate Director of the Charles F. and Joanne Knight Alzheimer's Disease Research Center. Dr. Goate is the recipient of numerous awards for her research, including the Potamkin Prize for Alzheimer's disease research, the Alzheimer's Association Zenith Award, and the Senior Investigator Award from the MetLife Foundation. She has worked on the genetics of Alzheimer's disease for 25 years. A pioneer in Alzheimer's disease research, Dr. Goate reported the first genetic mutation that causes an inherited form of Alzheimer's disease and was part of the teams that discovered genes that cause frontotemporal dementia and ALS. Her current research is focused on understanding the genetic risk factors for late onset Alzheimer's disease using genome-wide sequencing approaches and genome-wide association studies. Dr. Goate's group has pioneered the use of endophenotypes in the study of AD genetics. In particular, she has used cerebrospinal fluid biomarkers to identify novel genes and has been a contributor to two of the large consortia that have published GWAS studies (GERAD, ADGC). She has published more than 300 papers.

John Hardy, PhD was a lecturer at Imperial College where he led the group that found the first mutation in the amyloid gene that caused Alzheimer's disease. He moved to the US in 1992 and by 1998 was part of the consortium which identified mutations in the tau gene in Pick's disease. During 2001 at NIH, he was part of the group which found triplications in the synuclein gene that caused Parkinson's disease. He returned to the Institute of Neurology (UCL) in 2007 and most recently he led the group which found TREM2 variants in Alzheimer's disease– the first high risk variant for the disorder found in 20 years. His many awards include the Anna Marie Opprecht Prize for work on Parkinson's disease, several others for Alzheimer's disease, the 2011 Khalid Iqbal Lifetime Achievement Award, and IFRAO European Grand Prize. He is an elected member of the Academy of Medical Sciences, received an Honorary MD degree from the University of Umea, an F.R.S. from the Royal Society in 2009, and O.Sc. from the University of Newcastle in 2010.

Virginia Howard, PhD, FAHA, FSCT is a stroke epidemiologist with over 20 years of experience in multicenter, multidisciplinary clinical trials, longitudinal cohort studies, and related ancillary studies with a focus on stroke, cognitive functioning, stroke risk factors and health disparities. She is Professor of Epidemiology at the School of Public Health, University of Alabama at Birmingham. Dr. Howard received her PhD in epidemiology from the Medical University of South Carolina and an MSPH in biostatistics from the University of North Carolina at Chapel Hill. She is currently PI of an NIA-funded study aimed at identifying childhood and family socioeconomic factors that shape disparities in adult vascular and cognitive health. She is also co-PI of the REasons for Geographic And Racial Differences in Stroke (REGARDS) study, a longitudinal cohort study of 30,239 African American and white community-dwelling participants from the 48 contiguous United States. The overall goals of REGARDS are to better understand the factors contributing to the racial and geographic disparities in stroke mortality and cognitive functioning. She is also serving as the principal investigator for the Statistical and Data Management Center in the North American Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) that randomized 2502 patients with high-grade carotid stenosis to the two revascularization procedures. Dr. Howard is a co-author on over 130 peer-reviewed papers. Other relevant experience includes being chairperson of the subcommittee on "Bridges to Community: Assuring Ethical Conduct of Studies and Data Integrity" for an 2002 NIH-NINDS Advisory Panel on Stroke Disparities, current member of American Heart/Stroke Association (AHA/ASA) committees such as CVD and Stroke in Older Populations and the Minority Affairs Committee (Stroke Council), and discussion leader, NINDS Roundtable Discussions for Stroke Disparities Solutions, ASA International Stroke Conference (February 2011).

Edward (Ted) Huey, MD is a geriatric psychiatrist in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain and the Departments of Psychiatry and Neurology of Columbia University in New York City. He is board certified in neuropsychiatry. Dr. Huey's research has focused on patients with frontotemporal lobar degeneration (FTLD) and related disorders. He studies the genetics of FTLD and is interested in the range of phenotypes associated with mutations that can cause FTLD. He also uses imaging in patients with FTLD and brain injury to explore the neuroanatomy of complex behavior, social cognition, psychiatric disorders, and emotion. He is also interested in the role of the dopamine and serotonin systems in the pathogenesis and treatment of the symptoms of FTLD and related disorders. He is the recipient of a NIH/NINDS Pathway to Independence Award to research novel medication treatments and imaging biomarkers for FTLD.

Costantino Iadecola, MD is the Anne Parrish Titzell Professor of Neurology and Director of the Brain and Mind Research Institute at Weill Cornell Medical College, New York, a position he has held since 2012. Dr. Iadecola received the MD degree from the University of Rome, Italy, in 1977 and completed post-doctoral training and residency training in neurology at Cornell University Medical College-New York Hospital. After spending 10 years at the University of Minnesota, Dr. Iadecola was recruited back to Cornell in 2001 as Professor and Head of the Division of Neurobiology. Dr. Iadecola's research deals with the mechanisms of normal and abnormal cerebrovascular regulation, and on the molecular pathology of ischemic brain injury and neurodegeneration. A major area of interest relates to the interactions between cardiovascular risk factors, stroke, vascular dementia and Alzheimer's disease. Dr. Iadecola has published over 200 papers in peer-reviewed journals. He is active in several national and international research organizations and funding agencies. He has served on the Research Committee and on the Stroke Council of the American Heart Association (AHA) and has chaired the Program Committee of the International Stroke Conference. He participates in focus groups and review committees at the NIH. He has been President (Chair) of the Scientific Advisory Committee of the Fondation Leducq and is an advisor to the Canadian Stroke Network, the European Stroke Network, the German Stroke Network and the Institute of Stroke and Dementia Research (Munich, Germany). He is also a Member of the Scientific Council, DHU NeuroVascular disease Sorbonne (Paris, France) and of Stroke Research Planning Workgroup at NIH/NINDS. Dr. Iadecola has served as Associate Editor (2000-2010) and is currently Consulting Editor for Stroke, the leading journal for cerebrovascular diseases, and Reviewing Editor for the Journal of Neuroscience. He has received the Laurence McHenry Award from the American Academy of Neurology, the Louis Sklarow Memorial Award, the Established Investigator Award (AHA), the Jacob Javits Award from NIH/NINDS, and the Willis Award, the highest honor in stroke research bestowed by the AHA. In 2011, Dr. Iadecola received the Zenith Fellow Award from the Alzheimer's Association in support of his efforts to elucidate the role of vascular factors in Alzheimer's dementia.

Lori L. Jervis, PhD is an Associate Professor at the University of Oklahoma Department of Anthropology and a Director of the Center for Applied Social Research. Prior to taking a position at the University of Oklahoma, she was on the faculty at the American Indian and Alaska Native Programs in the Department of Psychiatry at the University of Colorado Denver. There she served as a principal ethnographer on a major psychiatric epidemiology study. A cultural/medical anthropologist as well as gerontologist, her work focuses on the intersection of culture, aging, and health. Dr. Jervis has led federally-funded research on cognitive impairment among American Indians. She has over two decades of research experience in gerontological anthropology and 16 years devoted specifically to American Indians. She has published numerous articles in psychiatric anthropology, gerontology, and neuropsychiatry, including two articles examining the performance of the Mini Mental State Exam and the Dementia Rating Scale-2 with American Indians in the Journal of Neuropsychiatry and Clinical Neurosciences. Dr. Jervis is immediate Past President of the Association of Anthropology and Gerontology.

Carol F. Lippa, MD is a board certified neurologist and physician scientist, certified in Geriatric Neurology, and has directed the Drexel University College of Medicine's Cognitive Disorders Program for 17 years. Her expertise is in translational and clinicopathologic studies in non- Alzheimer's dementias. Dr. Lippa is a member of the Scientific Advisory Board of the UK Lewy Body Society) and the Lewy Body Dementia Association (Chair 2004-2008). She participated in the first Dementia with Lewy Body workshop, and was on the organizing committee for the International Multidisciplinary Meeting for Dementia with Lewy Bodies and Parkinson's Disease Dementia: World Parkinson Congress Satellite (2006), and the Lewy Body Disease: Biomarker Symposium. (Washington, DC, 2010) as well as being Co-Chair for the 4th International Workshop on DLB and PDD (Japan, 2006). She has published widely on DLB and had an NIA grant entitled "Dementia with Parkinsonism: What are we diagnosing?"

Eng H. Lo, PhD uses in vitro and in vivo models to investigate the molecular mechanisms that underlie cell death after stroke and trauma, and to assess novel strategies for neuroprotection. The tools used comprise a combination of in vivo imaging, pharmacology, and molecular cell biology. Dr. Lo seeks to understand how perturbations in cell-cell and cell-matrix signaling mediate neurovascular dysfunction in brain injury and neurodegeneration.

Eliezer Masliah, MD received his MD from the National Autonomous University of Mexico, Mexico City in 1982. He completed his training in pathology in 1986 and in neuropathology and neurodegenerative disorders at the University of California, San Diego (UCSD) in 1989. Dr. Masliah is currently Professor at the Departments on Neurosciences and Pathology at UCSD, Director of the Laboratory of Experimental Neuropathology, and Director of the Autopsy Service at the UCSD- Medical Center. His work is focused on understanding the mechanisms of synaptic degeneration and propagation in Alzheimer's disease and Parkinson's disease, and at developing new therapeutics for these neurological disorders. He has published over 500 original research articles, 50 books chapters, and holds 10 patents.

Ian McKeith, MD is Professor of Old Age Psychiatry at the Institute for Ageing and Health at Newcastle University, UK. He is an NIHR Senior Investigator, a Director of the UK National Dementias and Neurodegenerative Diseases Research Network (DeNDRoN) and Clinical Theme Lead for the Newcastle BRU in Lewy Body dementias. His dementia research includes clinic- pathological brain banking studies, population based epidemiology, and clinical trials. He established the Consortium on Dementia with Lewy Bodies which developed consensus guidelines for diagnosis and treatment which are now used globally. He has published over 400 peer reviewed articles and in 2008 he received a lifetime achievement award from the UK Royal College of Psychiatrists.

Pamela J. McLean, PhD graduated from the University of Glasgow in 1990 with a BSc in Biochemistry and received her PhD in Pharmacology and Experimental Therapeutics from Boston University School of Medicine in 1998. Following a postdoctoral fellowship in the lab of Dr. Bradley Hyman at Massachusetts General Hospital/Harvard Medical School, Dr. McLean went on to become an Instructor and then Assistant Professor at Harvard Medical School. Dr. McLean's lab moved to the Mayo Clinic in Jacksonville, Florida in April of 2012 and she is now an Associate Professor in the Department of Neuroscience. Research in Dr. McLean's lab focuses on understanding the cellular and molecular mechanisms underlying neurodegeneration in Parkinson's disease, dementia with Lewy bodies, and related disorders. In particular, her research group studies the role of alpha- synuclein, a protein that is thought to be intimately involved in these diseases. Dr. McLean has published over 50 peer-reviewed original articles and reviews and her research is currently supported by two NIH grants.

Tom Mosley, PhD is the Guyton Distinguished Professor of Medicine (Geriatrics) and Neurology and Director of the Memory Impairment and Neurodegenerative Dementia (MIND) Center at the University of Mississippi Medical Center. His training includes a doctorate in clinical neuropsychology and behavioral neurology. Dr. Mosley's research efforts have been largely devoted to cardiovascular and population-based neuroepidemiologic studies seeking to identify the determinants of brain aging, neurocognitive decline, and racial disparities in dementia. He has designed the neurocognitive assessments and served as the principal investigator for several NIH- funded projects, including the Atherosclerosis Risk in Communities (ARIC) Study, ARIC Brain MRI study, ARIC Neurocognitive Study, Hispanic Community Health Study/Study of Latinos, and the Genetic Epidemiology Network of Arteriopathy (GENOA) study. Dr. Mosley currently chairs the neurocognitive working group for the international Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, and chairs the steering committee for the ARIC Neurocognitive Study, examining mid-life vascular risk factors for MCI/dementia in the ARIC cohort. In 2010, Dr. Mosley received the Bud Orgel Award for Distinguished Achievement in Research in Academic Health Centers by the American Psychological Association.

Richard O'Brien, MD, PhD received his undergraduate and medical degrees at Harvard University. He trained in medicine at the Massachusetts General Hospital and neurology at Johns Hopkins. His current work involves the effect of neurodegenerative disorders and stroke on synaptic plasticity in animal models of Alzheimer's disease and in humans at risk for Alzheimer's disease. He is a member of the leadership teams of the Baltimore Longitudinal Study of Aging and the BIOCARD study. Dr. O'Brien is the Chair of Neurology at the Bayview Campus of The Johns Hopkins Department of Neurology and is a Professor of Neurology, Neuroscience and Medicine. He is also the Associate Dean for Research at Johns Hopkins.

Sid O'Bryant, PhD is an Associate Professor in the Department of Internal Medicine at the University of North Texas Health Science Center. Dr. O'Bryant's primary area of research is the search for blood-based biomarkers of Alzheimer's disease. He leads this line of research through the Texas Alzheimer's Research & Care Consortium (TARCC), which has created and cross-validated a blood-based screener for AD analyzing data from both TARCC and Alzheimer's Disease Neuroimaging Initiative. His ongoing NIH research is further refining this algorithm, comparing assay results across serum and plasma as well as comparing results across multiple assay platforms. His overarching goal for this line of research is the generation of a cost-effective method for determining which patients and potential research participants receive follow-up neuroimaging or CSF biomarker analysis for confirmatory diagnosis of AD or other neurological diseases. Research focuses on investigating factors related to cognitive aging, including biomarkers, among Mexican Americans; his recent work has demonstrated that blood-biomarkers related to AD may vary according to ethnicity. His group is also studying how vascular and metabolic markers are related to cognitive dysfunction, AD and non-AD dementias among Mexican Americans. As a result of this work, he and others from across the globe initiated a working group designed to begin the process for establishing standards or best practices for the field of blood-based AD biomarkers, entitled STAR-B. Dr. O'Bryant completed his PhD in clinical psychology with a neuropsychology emphasis from the University at Albany. He then completed his neuropsychology internship at the University of Mississippi/Jackson VA consortium and his fellowship at the New Orleans VA Medical Center. His work has been funded by the National Institute on Aging, Environmental Protection Agency, the State of Texas as well as numerous private foundations. He has published over 100 research articles. He is a fellow of the National Academy of Neuropsychology and received the Early Career Award from that organization. He worked extensively with the Alzheimer's Association to create the Blood-Based Biomarker Group Professional Interest Area (PIA).

Chiadi Onyike, MD, MHS is Assistant Professor in the Department of Psychiatry and Behavioral Sciences in the Johns Hopkins University School of Medicine. Dr. Onyike is a specialist in neuropsychiatry and focuses on the care of individuals who have mid- and late-life dementias. He is Director of the Johns Hopkins Frontotemporal Dementias and Young-Onset Dementias Program. His research focuses on the epidemiology and neuropsychiatry of the frontotemporal dementias, practical dementia care, and treatment trials for Alzheimer's disease, frontotemporal dementias and related disorders. He serves on the Medical Advisory Council of the Association for Frontotemporal Dementias and the Board of Directors of the Alzheimer's Association in Maryland. He also served on the State of Maryland's Virginia I. Jones Commission on Alzheimer's Disease and Related Disorders that developed the Maryland Plan for Alzheimer's Disease and Related Disorders. After receiving his medical degree from the University of Nigeria, Dr. Onyike completed internships at the University of Nigeria Teaching Hospital and the St. Elizabeth's/CMHS in Washington DC, a fellowship in Neurochemistry/Cell Signaling at the University of Maryland at Baltimore, residency in Psychiatry at Johns Hopkins, and fellowships in Clinical Psychiatry and Psychiatric Epidemiology at Johns Hopkins. He also holds a graduate degree in Clinical Epidemiology.

Leonard Petrucelli, PhD is involved with translational research geared toward identifying and developing therapies for treatment and prevention of neurodegenerative diseases. Dr. Petrucelli has been on the forefront of research investigating the cellular mechanisms that cause neurodegeneration in diseases characterized by abnormal protein aggregation, such as Alzheimer's disease, frontotemporal lobar degeneration, and amyotrophic lateral sclerosis. His lab recently discovered that inhibition of the enzyme HDAC6 may be an effective strategy to effectively arrest the accumulation of tau in disease. Moreover, his team also discovered that a novel protein pathology, termed C9RANT (C9ORF72 dipeptide repeat), is generated as a result of repeat expansions in the C9ORF72 gene, which are the most common cause of ALS and FTD. In so doing, they uncovered a potential new therapeutic target and biomarker that may improve diagnosis of and prognosis for patients suffering from the two disorders. Dr. Petrucelli earned his PhD in molecular and cellular biochemistry at Loyola University and Stritch School of Medicine, Chicago. He is the principal investigator for several grants funded by the National Institutes of Health. His team's efforts to elucidate the role of TDP-43, tau and progranulin in neurodegeneration have significantly impacted the field as evidenced by the publication of dozens of articles, editorials, and book chapters in peer-reviewed journals such as Nature Medicine, The Proceedings of the National Academy of Sciences, Journal of Clinical Investigation, Journal of Neuroscience, and Neuron. Dr. Petrucelli has received the prestigious National Research Service Award from NIH; serves on numerous editorial boards, including Journal of Neuroscience; and is an invited member of the NIH Cellular and Molecular Biology of Neurodegeneration Study Section.

Bernard M. Ravina, MD is Medical Director, Translational Neurology, at Biogen Idec in Cambridge, MA. Dr. Ravina's research focuses on the development of biomarkers and therapeutics for neurodegenerative disorders. Dr. Ravina obtained his MD from Johns Hopkins University, completed residency training in Neurology and a Fellowship in Parkinson's disease and Movement Disorders at the University of Pennsylvania. Dr. Ravina received a Masters in Clinical Epidemiology and Biostatistics from the University of Pennsylvania Center for Clinical Epidemiology and Biostatistics. After completing training, he moved to the National Institute for Neurological Disorders and Stroke, where he developed a program of Phase II clinical trials in Parkinson's disease, and had oversight of clinical trials in stroke and ALS. Prior to joining Biogen Idec, Dr. Ravina was Associate Professor of Neurology, Director of the Movement and Inherited Neurological Disorders Unit, and Associate Chair of Neurology for Clinical Research at the University of Rochester School of Medicine and Dentistry.

Erik Roberson, MD, PhD is an Associate Professor of Neurology and Neurobiology and the Virginia B. Spencer Professor of Neuroscience at the University of Alabama at Birmingham, where he also serves as Associate Director of the Alzheimer's Disease Center. He received his A.B. with highest honors from Princeton University. He then earned his MD and PhD in neuroscience at Baylor College of Medicine in Houston. He completed a residency in neurology at the University of California San Francisco (UCSF), where he also served as Chief Resident in Neurology. After residency, he completed a clinical fellowship in behavioral neurology with Dr. Bruce Miller at UCSF and resumed basic research in the laboratory of Dr. Lennart Mucke at the Gladstone Institute of Neurological Disease, where he was responsible for studies showing the beneficial effects of tau reduction in mouse models of AD. In addition to continuing work on tau reduction, Dr. Roberson's laboratory is investigating mechanisms of social, emotional, and behavioral abnormalities in tau and progranulin models of FTD. Dr. Roberson also cares for patients in the Memory Disorders Clinic and conducts clinical trials for tauopathies.

Ralph L. Sacco, MD is the Chairman of Neurology, Olemberg Family Chair in Neurological Disorders, Miller Professor of Neurology, Epidemiology and Public Health, Human Genetics, and Neurosurgery, Executive Director of the Evelyn McKnight Brain Institute at the Miller School of Medicine, University of Miami, and Chief of the Neurology Service at Jackson Memorial Hospital. A graduate of Cornell University and a cum laude graduate of Boston University School of Medicine, he also holds a masters in epidemiology from Columbia University, School of Public Health. Dr. Sacco completed his neurology residency and postdoctoral training in Stroke and Epidemiology at Columbia Presbyterian in New York. He was previously Professor of Neurology, Chief of Stroke and Critical Care Division, and Associate Chairman at Columbia University before taking his current position as Chairman of Neurology at the University of Miami. He is the Principal Investigator of the Northern Manhattan Study and the Florida Puerto Rico Collaboration to Reduce Stroke Disparities as well as co-investigator of multiple other NIH grants. Dr. Sacco has published extensively with over 300 peer-reviewed articles in the areas of stroke prevention, treatment, epidemiology, risk factors, vascular cognitive impairment, human genetics, and stroke recurrence. His research has also addressed stroke and vascular disparities. Dr. Sacco has been the recipient of numerous awards, including the Feinberg Award of Excellence in Clinical Stroke, the Chairman's Award from the American Heart Association, and the NINDS Javits Award in neuroscience. Dr. Sacco is a fellow of both the Stroke and Epidemiology Councils of the American Heart Association and currently serves as Vice President of the American Academy of Neurology. He is a member of the American Association of Physicians and the American Neurological Association. He was the first neurologist to serve as the President of the American Heart Association, 2010-2011.

Clemens Scherzer, MD applies genomics approaches to identify causes, diagnostics, and therapeutics of Parkinson's disease and other neurodegenerative diseases. A neurologist at Brigham and Women's Hospital, he leads the Laboratory for Neurogenomics, co-directs the Harvard NeuroDiscovery Center Biomarker Study, and is Assistant Professor of Neurology at Harvard Medical School. A new path for developing treatments of Parkinson's disease may result from this team's finding of a molecular switch - the GATA-2 transcription factor - for the PD gene α- synuclein. Because too much -synuclein can lead to PD, Dr. Scherzer and his colleagues are now searching both for genetic variants that activate, and for therapeutic strategies that deactivate the molecular GATA-2- -synuclein switch. He uncovered a first candidate biomarker for PD based on gene expression in blood and originally associated abnormally low levels of the neuronal sorting receptor SORL1/LR11 with Alzheimer's disease, which led to its characterization as a "trafficking cop" in Amyloid- processing and important AD susceptibility gene. His lab is a one-stop-shop specialized in translational genomics applications to Parkinson's. The lab has an integrated workflow linking the longitudinal Harvard NeuroDiscovery Center Biomarker Study and its 2,000 patients biobank and the Global PD Gene Expression database, to genomics technologies, advanced in-lab bioinformatics and in-house high throughput validation by ABI 7900HT Real-Time PCR and Genotyping System.

Julie A. Schneider, MD is an Associate Professor of Pathology (Neuropathology) and Neurology at Rush University Medical Center and Rush Alzheimer's Disease Center in Chicago, IL. She completed her Neurology training at the University of Chicago and Neuropathology training at Emory University in Atlanta and is board certified in both specialties. Dr. Schneider has fellowship training in the neuropathology of dementia, is certified in Geriatric Neurology, and has a Master's Degree in Clinical Research with a focus in Epidemiology. She is the Associate Director and Neuropathology Core Leader of the Rush Alzheimer's Disease Center and the senior neuropathologist for the Religious Orders Study, the Rush Memory and Aging Project, and the Minority Aging Research Study. Dr. Schneider has extensive experience with clinical-pathologic epidemiologic studies of aging and dementia and has over 145 peer-reviewed publications and four book chapters. Dr. Schneider's research focuses on degenerative, vascular, and mixed brain pathologies and their role in age-related cognitive and motor decline. She is currently exploring risk factors, mechanisms, and the clinical expression of disease in persons with TDP-43 pathology and microvascular disease.

Ellen Sidransky, MD is Chief of the Section of Molecular Neurogenetics, and a pediatrician and clinical geneticist in the Medical Genetics Branch of the National Human Genome Research Institute at the NIH in Bethesda, MD. Dr. Sidransky received her B.A. in Biology from Brandeis University, Waltham, MA and MD from Tulane University, New Orleans, LA. She then trained in pediatrics at Children's Memorial Hospital/Northwestern University, and received her fellowship training in clinical genetics at the NIH Genetics Training Program. Dr. Sidransky has been a tenured investigator at NIH and a section chief since 2000. Her research includes both clinical and basic research aspects of Gaucher disease and Parkinson's disease, and she has spearheaded two large international collaborative studies regarding the genetics of Parkinson's disease and dementia with Lewy bodies. Her current work also focuses on understanding the complexity encountered in "simple" Mendelian disorders, the association between Gaucher disease and parkinsonism and the development of small molecule chaperone therapeutics. The author of over 150 publications, Dr. Sidransky directs two NIH clinical protocols, one evaluating patients with lysososmal storage disorders and the second prospectively studying patients and relatives with parkinsonism harboring GBA mutations.

David K. Simon, MD, PhD graduated from Johns Hopkins in 1986 and then obtained his MD and neuroscience PhD degrees from Washington University in St. Louis in 1993. He subsequently completed the Harvard Longwood Neurology Residency Program followed by a movement disorders fellowship at Massachusetts General Hospital. He now is on the faculty at Beth Israel Deaconess Medical Center and Harvard Medical School. Dr. Simon's laboratory studies mitochondrial dysfunction and neurodegeneration, with a focus on aging and on Parkinson's disease, including potential neuroprotective strategies. His lab conducts both basic and translational research, including behavioral, biochemical, histological, and molecular biological investigations of the impact of acquired (somatic) mitochondrial DNA mutations in the brain. His work includes studies of transgenic and toxin mouse models of PD and the POLG "mutator" mouse model of premature aging. Dr. Simon's laboratory also has investigated PGC-1α, a master regulator of mitochondrial biogenesis and antioxidant activities, as a neuroprotective target in aging and in PD, including gene therapy approaches to modulating PGC-1α activity. Dr. Simon is Co-Chair of the Scientific Review Committee of the Parkinson Study Group (PSG), and Co-Chair of the PSG Genetics and Environment Working Group. He also is on the Steering Committee of the NET-PD multicenter Phase II futility study of pioglitazone as a potential neuroprotective agent in PD, and is heading a biomarker substudy in association with this clinical study. He frequently reviews grants for the Michael J. Fox Foundation and is serving a 4-year term as a member of the NIH Molecular Neurogenetics study section.

Sidney Strickland, PhD received his BS in chemistry from Rhodes College in Memphis, and his PhD in biochemistry from the University of Michigan. He was a postdoctoral fellow at The Rockefeller University with Edward Reich. He was on the faculty of Rockefeller as an Assistant Professor and then Associate Professor. In 1983, he became Leading Professor at Stony Brook University. He returned to Rockefeller University in 2000 as Dean and Head of the Laboratory of Neurobiology and Genetics. His lab studies mechanisms of neurological disease.

Stephen Strittmatter, MD, PhD is a graduate of Harvard College and Johns Hopkins School of Medicine, and completed Neurology residency at Massachusetts General Hospital before joining the faculty of Yale School of Medicine. His laboratory research has focused on the molecular basis of cell surface receptors, initially focusing on factors regulating axonal guidance and neural repair, including Semaphorin/Plexin and Nogo/Nogo Receptor. His recent work in neurodegeneration has included the identification of Cellular Prion Protein as a high affinity receptor for Amyloid Beta oligomers in Alzheimer's disease, and the identification of Sortilin as a high affinity receptor for Progranulin in Frontotemporal Lobar Degeneration.

Bryan Traynor, MD, PhD is an Irish neurologist currently working in the US. He is an Investigator at the National Institute on Aging, and is also adjunct faculty at Johns Hopkins University. Dr. Traynor is best known for his work aimed at understanding the genetic etiology of amyotrophic lateral sclerosis (ALS) and related neurodegenerative diseases, such as frontotemporal dementia (FTD). He led the international consortium that identified pathogenic hexanucleotide repeat expansions in the C9ORF72 gene as a common cause of ALS and FTD. He has over a hundred publications in professional journals, and is a member of the Scientific Review Committee of The ALS Association, and of the Integration Panels for the Department of Defense ALS Research Program and the Department of Defense Alzheimer's Research Program. He has received numerous accolades throughout his career, including the NIH Director's Award, the Derek Denny- Brown Award, and the Sheila Essey Award for ALS Research.

Michael Tymianski, MD, PhD is a neurosurgeon specializing in the treatment of patients with brain vascular disorders, including surgery for stroke (carotid endarterectomy), brain aneurysms, arteriovenous malformations, cavernous malformations, and EC-IC bypass. He is Head of the Division of Neurosurgery at the Toronto Western Hospital, and is the Medical Director of the Neurovascular Therapeutics program at the University Health Network. He obtained his clinical specialty training first at the University of Toronto and then at the Barrow Neurological Institute, in Phoenix, AZ under Prof. Robert F. Spetzler. He is a professor of surgery at the University of Toronto. He teaches and supervises medical students, residents and clinical fellows. Dr. Tymianski studies the cellular and molecular mechanisms that cause brain cells to die during a stroke, and new drug treatments for protecting the brain from being damaged by stroke and other injuries.

John Van Swieten, MD, PhD has been involved in genetic, epidemiological, and pathological research on neurodegenerative diseases (FTLD, AD, Parkinson's disease, cerebellar ataxia) for the past 15 years. He has been the initiator and principal investigator of frontotemporal dementia research in the Netherlands over the last 20 years, with research focusing on four main areas: 1) genetic-epidemiological and clinical aspects of FTLD; 2) identification of genetic factors in hereditary forms of FTLD and their pathophysiological effects; 3) genotype-phenotype studies in hereditary forms of FTLD, and 4) functional MRI studies in presymptomatic carriers of PGRN and MAPT gene mutations. The first avenue of research has resulted in prevalence estimates of FTLD and the identification of several pathological forms. The second avenue has resulted in the identification of missense and splice-donor site mutations in the microtubule-associated protein tau (MAPT) and Progranulin (GRN) gene, and C9orf72 repeat expansions in several large families. He was involved in large genome wide association studies on FTD and progressive supranuclear palsy. Functional studies of specific MAPT missense mutations have been carried out, which have shown differential reduction of microtubule binding. The third avenue of his research has focused on the clinical and pathological phenotypes, resulting in a long list of genotype-phenotype publications, including those of MAPT, GRN, and C9orf72 gene mutations, and TDP-43 accumulation in hereditary FTLD with unknown gene defect. The fourth avenue is the functional network studies in patients with frontotemporal dementia, presymptomatic carriers, and Alzheimer's disease. Dr. Van Swieten is involved in the research on AD in a genetically isolated population which has led to significant linkage to chomosome 3 for familial AD, and to the association of several genetic factors with cognitive decline and hippocampal volume. Dr. Van Swieten is currently principal investigator of several whole exome sequencing projects in familial Alzheimer's disease in the Netherlands.

Cheryl Wellington, PhD obtained her PhD in Microbiology at the University of British Columbia in 1991 and did postdoctoral training at Harvard Medical School, the University of Calgary, and the University of British Columbia. She joined the Department of Pathology and Laboratory Medicine at the University of British Columbia in 2000 and was promoted to Professor in 2011. Dr. Wellington's research interests encompass lipid and lipoprotein metabolism in the brain and how this relates to chronic and acute neurological disorders. Dr. Wellington's group has made key contributions to the understanding of the role of apolipoprotein E (apoE) in Alzheimer's disease. Dr. Wellington's laboratory has shown that the amount of lipids carried on apoE affects the metabolism of Aβ peptides, which are toxic species that accumulate as amyloid plaques in the brains of patients with Alzheimer's disease and also accumulate in individuals who have suffered traumatic brain injury. Specifically, Dr. Wellington has identified the cholesterol transporter ABCA1 as the physiological transporter of lipids onto brain apoE. Her group has shown that mice deficient in ABCA1 have poorly-lipidated apoE in the brain and develop more amyloid, whereas transgenic mice that overexpress ABCA1 have lipid-rich apoE and have virtually no amyloid deposits. Her current research projects are aimed at developing methods to increase apoE lipidation in the brain for application to both Alzheimer's disease and traumatic brain injury.

Lon White, MD, MPH is a pediatrician and neuroepidemiologist at the Pacific Health Research and Education Institute in Honolulu. He established and directed the Honolulu-Asia Aging Study through its two decade data collection life, and now works to harvest the fruits of that effort through continuing analyses of the study's accrued data in collaboration with researchers at the National Institute on Aging, the University of Washington, and the University of Minnesota.

Keith Whitfield, PhD is the Vice Provost for Academic Affairs at Duke University. He holds appointments as Professor in the Department of Psychology and Neuroscience and Research Professor in the Department of Geriatric Medicine at Duke University Medical Center. He is also the co-Director of the Center on Biobehavioral Health Disparities Research. He has published more than 150 articles, books, and book chapters on cognition, health, and individual development and aging with a focus on African Americans. Dr. Whitfield's research examines the etiology of individual variation in health and individual differences in cognition due to health conditions. He has completed a study that involves examining health and psychosocial factors related to health among adult African American twins. His research on individuals has come from several data sets but mostly from his 14-year study called the Baltimore Study of Black Aging.

Donna Wilcock, PhD is an Assistant Professor in the Sanders-Brown Center on Aging and the Department of Physiology at the University of Kentucky in Lexington. Dr. Wilcock has an active research program focusing on the role of inflammation in Alzheimer's disease and vascular dementia. In particular, she is developing models to study the co-morbidity of Alzheimer's pathologies and cerebrovascular disease. Her ultimate goal is to enhance our understanding of inflammation in vascular dementia and Alzheimer's disease so that we can develop better, more personalized therapeutic interventions. Her research is currently funded by the National Institute of Neurological Disorders and Stroke, University of Kentucky Alzheimer's Disease Center and University of Kentucky Clinical and Translational Sciences Center.


SessionPresenters/Committee members
IntroductionStory Landis, Ron Petersen, Thomas Montine
Session 1:Alzheimer's Disease Related Dementias (ADRD) and Multiple Etiology Dementias: the Public Health Problem and Improving Recognition Across the SpectrumDavid Knopman, Bruce Miller, David Bennett, Brad Boeve, Cynthia Carlsson, Michael Geschwind, Ted Huey, Richard O'Brien
Session 2:Lewy Body DementiasDennis Dickson, Karen Marder, Dag Aarsland, Bradley Boeve, David Eidelberg, James Galvin, John Hardy, Carol Lippa, Eliezer Masliah, Ian McKeith, Pamela McLean, Bernard Ravina, Clemens Scherzer, Ellen Sidransky, David Simon
Session 3:Frontotemporal Dementia (FTD) and AD-Related TauopathiesMichael Hutton, William Seeley, Karen Ashe, Bradley Boeve, Adam Boxer, Nigel Cairns, Thomas Cooper, Marc Diamond, Karen Duff, Howard Feldman, Alison Goate, John Hardy, David Knopman, Leonard Petrucelli, Erik Roberson, Stephen Strittmatter, Bryan Traynor, John Van Swieten
Session 4:Vascular Contributions to ADRDSteven Greenberg, Berislav Zlokovic, Geert Jan Biessels, Monique Breteler, Helena C. Chui, Suzanne Craft, Costantino Iadecola, Eng H. Lo, Julie A. Schneider, Sidney Strickland, Michael Tymianski, Cheryl Wellington, Donna Wilcock
Session 5:Health Disparities in ADRDM. Maria Glymour, Jennifer Manly, Lisa Barnes, David Bennett, James Galvin, Virginia J. Howard, Lori L. Jervis, Thomas Mosley, Sid O'Bryant, Chiadi Onyike, Ralph Lewis Sacco, Lon White, Keith Whitfield
Concluding RemarksThomas Montine
Presentation of the Scientific Chair at the NINDS Advisory CouncilThomas Montine


Alzheimer's Disease-Related Dementias: Research Challenges and Opportunities (Day 1)

Alzheimer's Disease-Related Dementias: Research Challenges and Opportunities (Day 1)

Alzheimer's Disease-Related Dementias: Research Challenges and Opportunities (Day 2)

Alzheimer's Disease-Related Dementias: Research Challenges and Opportunities (Day 2)


This workshop is supported by:

The National Institute of Neurological Disorders and Stroke - logo

with contributions from:

The National Institute on Aging - logo
The Foundation for the National Institutes of Health - logo

and with generous sponsorship from:

The Alzheimer's Association - logo
Accelerate Cure/Treatments for Alzheimer's Disease - logo

The Association for Frontotemporal Degeneration - logo
US Against Alzheimer's Network - logo

Organizers and Roles in ADRD 2013

Roderick Corriveau, PhD, NINDS Program Director, NIH Conference Lead, Vascular Contributions to ADRD, Health Disparities

Debra Babcock, MD, PhD, NINDS Program Director, Lewy Body Dementias

Marian Emr, Director of the NINDS Office of Communications and Public Liaison

Wendy Galpern, MD, PhD, NINDS Program Director, Multiple Etiology Dementias

Richard Hodes, MD, NIA Director

Walter Koroshetz, MD, NINDS Deputy Director, Multiple Etiology Dementias, Vascular Contributions to ADRD

Andrey Kuzmichev, PhD, NINDS Program Analyst

Story Landis, PhD, NINDS Director

Creighton Phelps, PhD, NIA Program Director, Frontotemporal Dementia and Other Tauopathies

Beth‐Anne Sieber, PhD, NINDS Program Director, Lewy Body Dementias

Nina Silverberg, PhD, NIA Program Director, Health Disparities

Margaret Sutherland, PhD, NINDS Program Director, Frontotemporal Dementia and Other Tauopathies

Christine Torborg, PhD, NINDS Program Analyst

Salina Waddy, MD, NINDS Program Director, Health Disparities

Funding Announcements

RFA-AG-15-010: Interdisciplinary Research to Understand the Vascular Contributions to Alzheimer's Disease (R01)

Funding Opportunity Purpose: The goal of this funding opportunity announcement is to support interdisciplinary research that will lead to a greater understanding of the mechanisms by which vascular factors contribute to the complex etiology of Alzheimer's disease. Biomarker discovery for vascular contributions to Alzheimer’s dementia is also a key goal. [NB: The use of animal models is encouraged but not required. Applications relying solely on cell and animal models will be considered non-responsive and will not proceed to review.


Last Modified December 9, 2014