Document text
Principal Investigator: Fanny M Elahi
Organization: JAMES J PETERS VA MEDICAL CENTER
Fiscal Year: 2024
Funding agency: Veterans Affairs
Dr. Elahi is an early career physician-scientist with specialty training in neurodegenerative disease and
experience in biomarker development, who seeks to develop her career at the VA. By combining her clinical
and molecular biology training, Dr. Elahi's long-term goal is to contribute to a better understanding of
vascular pathways in neurodegenerative disorders in order to improve early diagnoses and
development of disease-modifying treatments that will alter the cognitive trajectory of so many
individuals affected with vascular disease and at risk of dementia. In order to achieve this goal, Dr. Elahi
seeks additional training to develop her knowledge and skills in two major domains: (1) leadership in medicine,
by starting a specialized clinic at the VA and UCSF, to evaluate veterans with VCID from a variety of causes,
high systemic vascular disease / risk, strokes, TBI, auto-immune disease, and neurodegenerative disease and
to undertake their enrollment into research, (2) advancement of her scientific skills in multi-modal data-driven
analytical approaches for unbiased biomarker discovery.
To better understand VCID, we need novel tools that can handle both the complexity of human disease
as well as the noisy nature of human-based biological and clinical data. Thus, novel approaches and methods
are needed. As a physician-scientist, Dr. Elahi is uniquely suited to pursue cutting-edge approaches to
advancement of diagnostics in VCID. However, with clinical training and responsibilities, she has not had the
opportunity to acquire adequate knowledge of unbiased biomarker discovery projects, nor the important
opportunity to develop her skills in advanced data-driven analytics.
In this application, Dr. Elahi proposes to use her clinical expertise in neurodegenerative disease and
technical expertise in exosomal technologies to undertake hypothesis-driven modelling of contributions of
endothelial inflammation and pathogenic angiogenesis to adverse clinical and radiographic brain outcomes in
VCID (Aims 1 and 2). While in Aim 3, in collaboration with her VA mentor, Dr. Ferguson, she will for the first
time undertake the analysis of multi-dimensional data, including exosomal proteomics, brain imaging, retinal
imaging, clinical variables and cognitive scores. The scope of the work proposed is aligned with Dr. Elahi’s
goal of becoming a leader in translational VCID research. The hypothesis and data-driven aims will provide
complimentary approaches to cutting-edge research in the field of neurodegenerative disease. This Aim will
provide the opportunity to undertake data-driven discovery of discrete clinical-biomarker endophenotypes
within a heterogenous cohort of subjects.
This research is expected to advance understanding of VCID with diagnostic and therapeutic relevance
and prepare Dr. Elahi for leadership in precision medicine approaches in VCID research. To ensure success of
the scientific and training goals of this work, Dr. Elahi has assembled a world-class team of leaders in vascular
neurology and neuroscience (Swanson), neurodegenerative disease (Miller), data science in neurological
disease (Ferguson), and advisors/collaborators in: epidemiology of vulnerable populations and causal
inference (Glymour), mutli-modal neuroimaging (Rosen), and cognition in VCID (Kramer). Dr. Elahi’s training
will involve a combination of individual tutorials with her mentors and scientific advisors, hands-on experience,
and formal coursework. The proposed research will provide Dr. Elahi with data for a larger prospective study of
microvascular disease in the veteran population with heterogenous etiologies: chronic and acute CVD related
to systemic vascular risk, TBI, and auto-immune/inflammatory disorders. She will propose a Merit Review
application submitted before the end of the CDA period. Dr. Elahi is enthusiastically committed to improving the
cognitive and mental health of Veterans through research, and with her proposed project and training, she will
develop a thriving research program in VCID at the VA.
Terms: <65 and older><65 or older><65 years of age and older><65 years of age or more><65 years of age or older><65+ years><65+ years old><> 65 years><AD dementia><AI system><Acute><Affect><Aged 65 and Over><Aging><Alzheimer Type Dementia><Alzheimer disease dementia><Alzheimer sclerosis><Alzheimer syndrome><Alzheimer's><Alzheimer's Disease><Alzheimers Dementia><Amentia><Apoplexy><Area><Armed Forces Personnel><Arteriosclerotic Dementia><Artificial Intelligence><Astrocytes><Astrocytus><Astroglia><Autoimmune><Autoimmune Diseases><Autoregulation><Behavior><Big Data><BigData><Biological><Biological Markers><Blood><Blood Reticuloendothelial System><Blood Vessels><Brain><Brain Nervous System><Brain Trauma><Brain Vascular Accident><Brain imaging><Causality><Cell Body><Cells><Cerebral Stroke><Cerebrovascular Apoplexy><Cerebrovascular Stroke><Chronic><Clinic><Clinical><Clinical Data><Cognition><Cognitive><Cognitive Disturbance><Cognitive Impairment><Cognitive decline><Cognitive function abnormal><Collaborations><Computer Reasoning><DNA Molecular Biology><Data><Data Analytics><Data Collection><Data Science><Degenerative Disorder><Degenerative Neurologic Disorders><Dementia><Development><Diagnostic><Disease><Disease Progression><Disorder><Dissection><Disturbance in cognition><Dysfunction><Early Diagnosis><Emotional><Encephalon><Endothelium><Enrollment><Ensure><Epidemic><Epidemiology><Etiology><Face><Failure><Fibrosis><Functional disorder><Funding><General Population><General Public><Glia><Glial Cells><Goals><Homeostasis><Human Characteristics><Human Nature><Image><Impaired cognition><Impairment><Individual><Inflammation><Inflammatory><Injury><Intervention><Intervention Strategies><Investigators><Knowledge><Kolliker's reticulum><Leadership><MT-bound tau><Machine Intelligence><Machine Learning><Mediating><Mediation><Medicine><Mental Health><Mental Hygiene><Mentors><Mentorship><Metabolic Diseases><Metabolic Disorder><Methods><Microvascular Dysfunction><Military><Military Personnel><Modality><Modeling><Molecular><Molecular Biology><NINDS><National Institute of Neurological Diseases and Stroke><National Institute of Neurological Disorders and Stroke><Natural regeneration><Negotiating><Negotiation><Nerve Cells><Nerve Degeneration><Nerve Unit><Nervous System Degenerative Diseases><Nervous System Diseases><Nervous System Disorder><Neural Cell><Neural Degenerative Diseases><Neural degenerative Disorders><Neurocyte><Neurodegenerative Diseases><Neurodegenerative Disorders><Neuroglia><Neuroglial Cells><Neurologic Degenerative Conditions><Neurologic Disorders><Neurological Disorders><Neurology><Neuron Degeneration><Neurons><Neurosciences><Non-neuronal cell><Nonneuronal cell><Outcome><Pathogenicity><Pathologic Angiogenesis><Pathologic Neovascularization><Pathological Angiogenesis><Pathological Neovascularization><Pathology><Pathway interactions><Patients><Pattern><Perfusion><Phase><Phenotype><Physicians><Physiological Homeostasis><Physiopathology><Play><Primary Senile Degenerative Dementia><Prospective Studies><Proteomics><Psychological Health><Radiography><Regeneration><Research><Research Personnel><Researchers><Risk><Roentgenography><Role><Scientific Advances and Accomplishments><Scientist><Services><Site><Specialty><Stroke><Synapses><Synaptic><System><Technical Expertise><Techniques><Technology><Testing><Therapeutic><Thesaurismosis><Time><Toxicant exposure><Training><Traumatic Brain Injury><Vascular Cognitive Impairment><Vascular Dementia><Vascular Diseases><Vascular Disorder><Veterans><Vulnerable Populations><Work><abnormal protein homeostasis><abnormal proteostasis><above age 65><accurate diagnostics><after age 65><age 65 and greater><age 65 and older><age 65 or older><age > 65><age of 65 years onward><aged 65 and greater><aged 65+><aged group><aged groups><aged individual><aged individuals><aged people><aged person><aged persons><aged population><aged populations><aged ≥65><aging population><angiogenesis><astrocytic glia><autoimmune condition><autoimmune disorder><autoimmunity disease><bio-markers><biologic><biologic marker><biomarker><biomarker development><biomarker discovery><biomarker identification><biomed informatics><biomedical informatics><blood vessel disorder><brain attack><brain visualization><cardiac disease induced cognitive impairment><career><causation><cerebral vascular accident><cerebral vascular biology><cerebrovascular accident><cerebrovascular biology><clinical biomarkers><clinical phenotype><clinical training><clinically useful biomarkers><cognitive assessment><cognitive dysfunction><cognitive loss><cognitive testing><cohort><defective proteostasis><degenerative condition><degenerative disease><degenerative diseases of motor and sensory neurons><degenerative neurological diseases><dementia risk><developmental><diagnostic biomarker><diagnostic marker><disease causation><disease subgroups><disease subtype><disorder subtype><drug development><early detection><endophenotype><enroll><epidemiologic><epidemiological><exosome><experience><faces><facial><high dimensional data><human disease><human old age (65+)><hypoperfusion><identification of biomarkers><identification of new biomarkers><imaging><improved><injuries><interventional strategy><machine based learning><marker identification><medical specialties><metabolism disorder><microtubule bound tau><microtubule-bound tau><microvascular complications><microvascular disease><military population><military veteran><molecular biomarker><molecular marker><multi-modal data><multi-modal datasets><multidimensional data><multidimensional datasets><multimodal data><multimodal datasets><nerve cement><neural degeneration><neural imaging><neural inflammation><neuro-imaging><neuro-vascular><neurodegeneration><neurodegenerative><neurodegenerative illness><neuroimaging><neuroinflammation><neuroinflammatory><neurological degeneration><neurological disease><neurological imaging><neuronal><neuronal degeneration><neurovascular><new approaches><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutics><new therapy><next generation therapeutics><novel><novel approaches><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel strategies><novel strategy><novel therapeutics><novel therapy><old age><over 65 years><p-tau><p-τ><pathophysiology><pathway><phenotypic biomarker><phenotypic marker><phospho-tau><phospho-τ><phosphorylated tau><population aging><post-translational modification of tau><post-trauma stress><post-traumatic stress><posttranslational modification of tau><posttrauma stress><posttraumatic stress><precision medicine><precision-based medicine><predictive signature><primary degenerative dementia><programs><prospective><protein homeostasis decline><protein homeostasis deficiency><protein homeostasis dysfunction><protein homeostasis failure><protein homeostasis loss><proteostasis decline><proteostasis defect><proteostasis deficiency><proteostasis dysfunction><proteostasis dysregulation><proteostasis failure><proteostasis impairment><proteostasis loss><radiologic imaging><radiological imaging><regenerate><resilience><resilient><retina imaging><retinal imaging><risk factor for dementia><risk for dementia><scientific accomplishments><scientific advances><senile dementia of the Alzheimer type><skills><small vessel disease><social role><stroked><strokes><success><synapse><tau><tau Proteins><tau factor><tau phosphorylation><tau posttranslational modification><tau-1><technical skills><therapeutic agent development><therapeutic development><tool><toxic exposure><traumatic brain damage><unsupervised learning><unsupervised machine learning><vascular><vascular and cognitive impairment><vascular cognition impairment><vascular cognitive decline><vascular cognitive disease><vascular cognitive dysfunction><vascular cognitive impairment and dementia><vascular contributions to cognition/dementia><vascular contributions to cognitive impairment><vascular contributions to cognitive impairment and dementia><vascular contributions to dementia><vascular dysfunction><vascular related cognitive decline><vascular related cognitive impairment><vasculopathy><veteran population><vulnerable group><vulnerable individual><vulnerable people><τ Proteins><τ phosphorylation><≥65 years>