UNDERSTANDING THE MECHANISMS LINKING SMALL VESSEL CEREBROVASCULAR DISEASE AND ALZHEIMER'S DISEASE PATHOPHYS…
Federal financial assistance recorded from USAspending. This is not a procurement contract.
Assistance award details
- Assistance award identifier
- ASST_NON_R00AG065506_075
- FAIN
- R00AG065506
- Recipient
- THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK
- Awarding agency
- Department of Health and Human Services
- Funding agency
- Department of Health and Human Services
- Assistance listing (CFDA)
- 93.866
- Total obligated
- $742,017
- Period
- Jul 1, 2021 – Feb 28, 2026
- Fiscal year
- 2023
- Place of performance state
- NY
- Source file
- FY2023_All_Assistance_Full_20261006.zip
Description
UNDERSTANDING THE MECHANISMS LINKING SMALL VESSEL CEREBROVASCULAR DISEASE AND ALZHEIMER'S DISEASE PATHOPHYSIOLOGY WITH NEURODEGENERATION AND COGNITION DURING MIDLIFE - PROJECT SUMMARY THE OVERALL GOAL OF THIS K99/R00 PROPOSAL IS TO ELUCIDATE THE EXTENT TO WHICH SMALL VESSEL CEREBROVASCULAR DISEASE (SVCBVD) AND ALZHEIMERâS DISEASE (AD) PATHOPHYSIOLOGY ARE ADDITIVE OR SYNERGISTIC IN THEIR EFFECTS ON NEURODEGENERATION AND COGNITION IN MIDLIFE, AND TO DETERMINE IF THAT DIFFERS ACROSS RACIAL/ETHNIC GROUPS. COMORBID SVCBVD AND AD PATHOLOGY IS OBSERVED IN MOST DEMENTIA CASES AT AUTOPSY, AND IS MORE PREVALENT IN RACIAL/ETHNIC MINORITIES. EVIDENCE IS BUILDING THAT SVCBVD HAS DETRIMENTAL EFFECTS ON AMYLOID CLEARANCE AND TAU PHOSPHORYLATION, WHICH EXACERBATES NEURODEGENERATION AND COGNITIVE IMPAIRMENT IN AD. IT IS CRUCIAL TO INCLUDE SVCBVD, AMYLOID, AND TAU WHEN CONSIDERING PRIMARY DRIVERS OF DISEASE, AND NEURODEGENERATION AND COGNITION WHEN CONSIDERING THE CONSEQUENCES OF THOSE PRIMARY DRIVERS. WHILE INITIAL COGNITIVE IMPAIRMENTS IN SVCBVD ARE IN EXECUTIVE FUNCTION AND THOSE IN AD ARE IN MEMORY, THE CONSEQUENCES OF THE TWO BECOME LESS DISTINCT WHEN THEY CO-OCCUR. EQUALLY AS IMPORTANT, STUDIES IN MIDLIFE ARE NECESSARY TO ELUCIDATE HOW SVCBVD AND AD PATHOPHYSIOLOGY INITIALLY DEVELOP, AND HOW A PARTICULAR MIXTURE OF AD AND SVCBVD INFLUENCES DISEASE PROGRESSION. AIM 1 (K99) DETERMINES THE BIOLOGICAL CONSEQUENCE THAT SVCBVD AND AMYLOID HAVE ON TAU- RELATED NEURODEGENERATION, AND EXPLORES RACIAL/ETHNIC DIFFERENCES IN THESE ASSOCIATIONS. AIM 2 (K99) DETERMINES THE COGNITIVE CONSEQUENCE THAT SVCBVD AND AMYLOID HAVE ON TAU-RELATED MEMORY DYSFUNCTION, AND EXPLORES RACIAL/ETHNIC DIFFERENCES IN THESE ASSOCIATIONS. THE CENTRAL HYPOTHESIS IS THAT, IN MIDDLE AGE, INDIVIDUALS WITH SVCBVD DEMONSTRATE MORE AD-RELATED NEURODEGENERATION AND SUBSEQUENTLY MORE COGNITIVE IMPAIRMENT, AND THAT THIS EFFECT WILL BE STRONGER IN RACIAL/ETHNIC MINORITIES DUE TO THE HIGHER PREVALENCE OF SVCBVD. TO ACHIEV