TOWARDS A COMPREHENSIVE NEUROMETABOLIC PROFILE IN PATIENTS WITH MILD COGNITIVE IMPAIRMENT. - PROJECT SUMMAR…

Assistance award details

Assistance award identifier

ASST_NON_R00AG062230_075

FAIN

R00AG062230

Recipient

THE JOHNS HOPKINS UNIVERSITY

Awarding agency

Department of Health and Human Services

Funding agency

Department of Health and Human Services

Assistance listing (CFDA)

93.866

Total obligated

$722,056

Period

Apr 15, 2021 – Mar 31, 2024

Fiscal year

2021

Place of performance state

MD

Source file

FY2021_All_Assistance_Full_20261006.zip

Description

TOWARDS A COMPREHENSIVE NEUROMETABOLIC PROFILE IN PATIENTS WITH MILD COGNITIVE IMPAIRMENT. - PROJECT SUMMARY AS GLOBAL LIFE EXPECTANCY CONTINUES TO GROW, THE PREVALENCE OF ALZHEIMER’S DISEASE (AD) IS EXPECTED TO DOUBLE EVERY 20 YEARS UNTIL 2040. THE COGNITIVE DECLINE ASSOCIATED WITH AD HAS DEVASTATING IMPACT ON THE QUALITY OF LIFE AND LIFESPAN OF AFFECTED INDIVIDUALS, AND THE ENORMOUS SOCIETAL AND ECONOMIC CONSEQUENCES – CURRENTLY AROUND $100B PER YEAR IN THE UNITED STATES ALONE – ARE ONE OF THE MAJOR CHALLENGES OF THE 21ST CENTURY. THE PREVENTIVE TREATMENT NECESSARY TO MITIGATE THE IMPACT OF AD REQUIRES EARLY IDENTIFICATION OF SUBJECTS AT RISK AND RELIABLE PREDICTORS OF DISEASE PROGRESSION. DEVELOPING SUCH EARLY-INTERVENTION STRATEGIES REQUIRES A THOROUGH UNDERSTANDING OF THE NEUROBIOLOGICAL BASIS OF AD AND ITS PRECLINICAL STAGES, SUCH AS MILD COGNITIVE IMPAIRMENT (MCI). BASIC AND CLINICAL RESEARCH HAS ESTABLISHED KEY PATHOPHYSIOLOGICAL PROCESSES IN MCI/AD DEVELOPMENT, INCLUDING DEPOSITION OF AMYLOID-B AND TAU PROTEINS, MITOCHONDRIAL DYSFUNCTION, OXIDATIVE STRESS, AND DISTURBED NEUROTRANSMISSION. FEW STUDIES HAVE ELUCIDATED THE INTERACTIONS BETWEEN THESE PROCESSES, AND THEIR INTERACTIONS AND RELATIONSHIPS ULTIMATELY LEADING TO COGNITIVE DECLINE REMAIN POORLY UNDERSTOOD. RECENT ADVANCES IN EDITED MAGNETIC RESONANCE SPECTROSCOPY (MRS) TECHNIQUES HAVE OPENED A NEW AVENUE TO STUDY THE ROLES OF MULTIPLE LOW-CONCENTRATION BRAIN METABOLITES IN VIVO WITH GREATLY REDUCED EXAMINATION TIMES. IT IS NOW POSSIBLE TO SIMULTANEOUSLY DETERMINE LEVELS OF NEUROTRANSMITTERS AND NEUROMODULATORS (GABA, GLUTAMATE, N-ACETYLASPARTYLGLUTAMATE, ASPARTATE), REDOX COMPOUNDS (GLUTATHIONE, ASCORBATE), AND INDICATORS OF MITOCHONDRIAL DYSFUNCTION (LACTATE) AND NEURONAL INTEGRITY (N-ACETYLASPARTATE). THE INITIAL GOAL OF THIS PROPOSAL IS TO EXTEND THE SPATIAL COVERAGE OF THESE MULTI-METABOLITE METHODS, WHICH ARE CURRENTLY RESTRICTED TO SINGLE-VOXEL MEASUREMENTS, BY ADVANCING THEM INTO MULTI-VO