Project Grant R21NS137281
- This $1,120,805 Project Grant award from the National Institute of Neurological Disorders and Stroke (NINDS), under the Extramural Research Programs in the Neurosciences and Neurological Disorders federal grant program (CFDA 93.853), will support research to investigate how prior SARS-CoV-2 infection may increase the risk of vascular contributions to cognitive impairment and dementia (VCID). The research aims to: Determine how prior SARS-CoV-2 infection influences blood-brain barrier...
- This Project Grant award of $5,949,022, provided by the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) program, will fund research to identify novel therapeutic targets for treating cerebral amyloid angiopathy (CAA) and vascular contributions to cognitive impairment and dementia (VCID). The research, led by the Jackson Laboratory with sub-awards to Emory University, Rush...
- This Project Grant award for $2,398,590.00, provided by the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) program, will support research to investigate the role of brain microcirculation and capillary endothelial cell energetics in the development of vascular cognitive impairment and dementia (VCID) observed in Alzheimer's disease (AD) and AD-related dementias. The...
- This Project Grant award, funded by the National Institute on Aging (NIA) under the Aging Research federal grant program (CFDA 93.866), aims to investigate the impact of SARS-CoV-2 infection on the cerebrovascular system and its role in increasing the risk of Vascular Contributions to Cognitive Impairment and Dementia (VCID). The $2,549,080 award to the University of Illinois will support research over a 4-year period to determine how prior SARS-CoV-2 infection influences blood-brain barrier...
- This federal Project Grant award, issued by the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) program, provides $4,693,249 to the University of California, Los Angeles (UCLA) to conduct research on defining the molecular spectrum of white matter vascular lesions that drive vascular cognitive impairment and dementia (VCID). The project aims to develop a better understanding of...
- This Project Grant award from the National Institute of Neurological Disorders and Stroke (NINDS), under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853), provides $776,503 to The General Hospital Corporation (Massachusetts General Hospital) to investigate the role of perivascular inflammation and vascular remodeling in cerebral small vessel diseases (CSVD), which can lead to intracerebral hemorrhage. The project will leverage autopsy cases and mouse...
- The University of Wisconsin System has been awarded a $640,906 Project Grant by the National Institute on Aging (CFDA 93.866 - Aging Research) for the project "Elucidating Cerebrovascular Disease Pathways to Cognitive Decline with Vascular Neuroimaging." The project aims to address the knowledge gap in accurately diagnosing and effectively treating the vascular contributions to cognitive impairment and dementia (VCID), as well as Alzheimer's disease with comorbid cerebrovascular...
- This federal Project Grant award for $633,146 from the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) program supports research to determine modifiable factors for post-stroke vascular cognitive impairment and dementia (VCID). The key objectives are to: 1) quantify the association between performance of cognitively stimulating activities after stroke and post-stroke cognitive...
- This Project Grant award of $149,264 from the National Institute of Neurological Disorders and Stroke (NINDS) Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) will support research investigating the contributions and impact of neutrophil activity in a comorbid model of Alzheimer's disease (AD) and vascular contributions to cognitive impairment and dementia (VCID). The research aims to examine the mechanisms by which neutrophils contribute to worsened...
- The National Institute on Aging (NIA) awarded a $2,244,471 Project Grant under CFDA 93.866 (Aging Research) to Oregon Health & Science University (OHSU) to develop a first-in-class, CNS-penetrant small molecule agonist for G protein-coupled receptor 39 (GPR39) as a potential treatment for vascular cognitive impairment and dementia (VCID). The 3-year project from September 2023 to August 2026 will use in vitro and in vivo assays to identify lead compounds, determine their safety and...
NEUROVASCULAR CALCIFICATION: CONSEQUENCES AND TREATMENT - PATHOPHYSIOLOGY OF VASCULAR CONTRIBUTIONS TO COGNITIVE IMPAIRMENT AND DEMENTIA (VCID), INCLUDING VASCULAR COGNITIVE IMPAIRMENT, REMAINS ENIGMATIC, AND THIS PROJECT WILL TAKE A NOVEL FOCUS BY ADDRESSING THE POSSIBLE ROLE OF CALCIFICATION OF THE INTRACRANIAL VASCULATURE. WE WILL ANALYZE THE CONSEQUENCES OF NEUROVASCULAR CALCIFICATION (NVC) ON BRAIN PARENCHYMA AND SUBSEQUENT IMPACT ON COGNITION IN A HIGH-RISK POPULATION OF AGING AND CHRONIC KIDNEY DISEASE (CKD) SUBJECTS/PATIENTS. WE WILL DELINEATE THE SPECIFIC PATTERN OF CALCIFICATION (INTIMAL VS MEDIAL ARTERIAL/ARTERIOLAR AND CAPILLARY) AND ANALYZE ISCHEMIC AND HEMORRHAGIC INJURY IN AUTOPSY HUMAN BRAIN. WE WILL ALSO EXAMINE THE PROCESS OF NVC IN MOUSE BRAIN, ITS IMPACT ON PARENCHYMAL INJURY AND COGNITIVE IMPAIRMENT, AND DETERMINE HOW IT MAY BE TREATED OR PREVENTED. VASCULAR CALCIFICATION IS AGE-DEPENDENT, AND WE WILL FOCUS ON AGING IN OUR STUDIES. BECAUSE CKD IS KNOWN TO PROFOUNDLY ADVANCE CALCIFICATION OF VASCULATURE, WE WILL ALSO FOCUS ON CKD IN OUR STUDIES. THE PROJECT TEAM HAS EXPERTISE IN STROKE NEUROLOGY, VASCULAR NEUROBIOLOGY, NEPHROLOGY, NEUROPATHOLOGY, AND BIOSTATISTICS, ALL RELEVANT TO THE PROPOSAL: SPECIFIC AIM 1: TO DETERMINE THE RELATIONSHIP BETWEEN NVC AND MICROVASCULAR DISEASE IN CKD OF AGING. HYPOTHESIS 1A: NVC (MEDIAL VS INTIMAL/CAPILLARY) PREDICTS MICROVASCULAR ISCHEMIC INJURY IN AUTOPSY BRAIN OF AGED CKD SUBJECTS. HYPOTHESIS 1B: NVC (MEDIAL VS INTIMAL/CAPILLARY) PREDICTS MICROVASCULAR HEMORRHAGIC INJURY IN AUTOPSY BRAIN OF AGED CKD SUBJECTS. SPECIFIC AIM 2: TO DETERMINE A) THE EFFECTS OF NVC ON BRAIN PARENCHYMA AND COGNITIVE PERFORMANCE, AND B) THE MECHANISTIC TREATMENT OF NVC, IN AGED CKD MICE. HYPOTHESIS 2A: NVC WORSENS MICROVASCULAR PARENCHYMAL INJURY AND VCID WITH COGNITIVE DECLINE IN AGED CKD MICE. HYPOTHESIS 2B: ANTI-CALCIFICATION THERAPIES DECREASE NVC AND PARENCHYMAL INJURY AND IMPROVE COGNITIVE PERFORMANCE IN AGED CKD MICE. OUR PROPOSED PROJECT COMBINES HUMAN AUTOPSY INVESTIGATION WITH A RELEVANT MOUSE MODEL, DESIGNED TO PRODUCE PROJECT SYNERGY IN WHICH OBSERVATIONS FROM THE HUMAN STUDY INFORM THE MOUSE INVESTIGATION AND MOUSE STUDIES SUGGEST TARGETABLE MECHANISMS OF NVC IN HUMAN BRAIN. INCORPORATION OF THE MOUSE MODEL PROVIDES THE ADVANTAGE OF A TRIAL OF TARGETED THERAPY FOR NVC, WHICH IS TO THE BEST OF OUR KNOWLEDGE THE FIRST SUCH ATTEMPT. OUR HUMAN AUTOPSY STUDY WILL COMPARE CKD VS NON-CKD SUBJECTS, AND THUS INSIGHTS WILL BE GENERATED FOR BOTH THE CKD AND NON-CKD POPULATION. COMPLETION OF THIS PROJECT BY OUR UNIQUE MUTLI- DISCIPLINARY TEAM SHOULD PAVE THE WAY FOR MORE COMPREHENSIVE STUDIES OF NVC AND ITS TREATMENT, PROVIDING NEW DIRECTIONS IN THE SCIENTIFIC APPROACH TO AMELIORATING VCID, INCLUDING VASCULAR COGNITIVE IMPAIRMENT.
Mod # | Description | ReasonForModification | Federal Obligation | Date |
|---|---|---|---|---|
| Not listed | $217.2k | 5/9/25 | ||
| Not listed | $181.0k | 5/15/24 | ||
| Not listed | $181.0k | 5/15/24 |