Project Grant K01DA060092

BRAIN AGE OF PEOPLE WITH HIV AND HISTORY OF METHAMPHETAMINE USE - PROJECT SUMMARY NEUROIMAGING STUDIES SHOW A RELATIONSHIP BETWEEN ACCELERATED BIOLOGICAL AGING AND ACCELERATED BRAIN ATROPHY EVEN IN HEALTHY POPULATIONS. RECENT MACHINE LEARNING APPROACHES HAVE USED NEUROIMAGING VARIABLES, SUCH AS CORTICAL THICKNESS AND SUBCORTICAL VOLUME, TO CALCULATE AN ESTIMATED "BRAIN AGE" AS A MEASURE OF BIOLOGICAL AGING. ESTIMATED BRAIN AGE GREATER THAN AN INDIVIDUAL'S CHRONOLOGICAL AGE IS THOUGHT TO REFLECT AN ACCELERATED RATE OF AGE-RELATED CHANGES TO THE BRAIN AND MAY PREDICT FUTURE IMPAIRMENTS IN COGNITIVE FUNCTIONING. ACCELERATED BIOLOGICAL BRAIN AGING MAY OCCUR AMONG PEOPLE WITH HIV (PWH), AS CENTRAL NERVOUS SYSTEM COMPLICATIONS FROM HIV INFECTION MAY OCCUR EVEN IN INDIVIDUALS TAKING ANTIRETROVIRAL THERAPY (ART). METHAMPHETAMINE (METH) USE, WHICH IS COMMON AMONG PWH, MAY ALSO BE DETRIMENTAL TO BRAIN HEALTH. IT IS HYPOTHESIZED THAT METH'S EFFECTS ON THE CENTRAL NERVOUS SYSTEM MAY HAVE A SYNERGISTIC EFFECT ON THE LONG-TERM IMPACT OF HIV INFECTION. THIS K01 APPLICATION WILL USE STRUCTURAL AND FUNCTIONAL NEUROIMAGING MEASURES TO DEVELOP A NORMATIVE MODEL OF BRAIN AGE USING DATA FROM THE HUMAN CONNECTOME PROJECT TO LEVERAGE HYPOTHESIS TESTING IN A LOCALLY COLLECTED DATASET BY THE UC SAN DIEGO TRANSLATIONAL METHAMPHETAMINE AIDS RESEARCH CENTER (TMARC) THAT INCLUDES ADULTS STRATIFIED BY HIV INFECTION AND METHAMPHETAMINE USE. SPECIFIC AIM 1 WILL ESTIMATE BRAIN AGE IN THE TMARC COHORT USING A COMPOSITE MEASURE OF CORTICAL THICKNESS AND SUBCORTICAL VOLUME DERIVED FROM T1-WEIGHTED STRUCTURAL SCANS AND COMPARE IT TO CHRONOLOGICAL AGE AND COGNITIVE MEASURES. WE HYPOTHESIZE THAT HIV INFECTION AND METH USE WILL INDIVIDUALLY ACCELERATE BRAIN AGE, BUT THAT THEIR COMBINED EFFECTS WILL BE ASSOCIATED WITH GREATER ACCELERATED AGING. SPECIFIC AIM 2 WILL INTEGRATE T1-WEIGHTED AND RESTING-STATE FUNCTIONAL NEUROIMAGING SCANS TO DEVELOP A BRAIN-AGE MODEL BASED ON MULTI-MODAL NEUROIMAGING DATA WHICH IS HYPOTHESIZED TO BE MORE SENSITIVE TO THE EFFECTS OF METH USE AND HIV STATUS ON BRAIN AGE AND COGNITIVE MEASURES. SPECIFIC AIM 3 WILL INVESTIGATE WHETHER INFLAMMATION INDEXED BY CRP, MCP-1 AND NFL FROM CEREBROSPINAL FLUID HAS AN INDIRECT EFFECT ON THE ASSOCIATION BETWEEN BRAIN AGE AND HISTORY OF METH USE OR BETWEEN BRAIN AGE AND HIV STATUS. DISENTANGLING THE BIOLOGICAL EFFECTS OF HIV IN OLDER ADULTS AND ITS RELATION TO HISTORY OF METH USE WILL ADVANCE THE HIV FIELD THROUGH INFORMING OUR UNDERSTANDING OF HOW BIOMARKERS OF NEURAL INTEGRITY AND INFLAMMATION RELATED TO COGNITION, WHICH MAY INFORM FUTURE HEALTH INTERVENTIONS. THIS K01 APPLICATION HAS BROAD, LONG-TERM OBJECTIVES THAT INCLUDE OBTAINING EXPERIENCE IN DATA-SCIENCE METHODOLOGIES USING NEUROIMAGING DATA IN ORDER TO GENERATE MODELS THAT WILL PUSH NEUROIMAGING RESEARCH TOWARDS MORE CLINICAL APPLICATIONS IN SUBSTANCE USE AND HIV INFECTION. THIS PROPOSED K01 PROJECT WILL PROVIDE THE APPLICANT WITH CRITICAL TRAINING IN DATA SCIENCE USING NEUROIMAGING DATA, WHICH WILL BROADEN HER RESEARCH SKILL-SET AND PROVIDE PRELIMINARY FINDINGS FOR THE PREPARATION OF AN R-LEVEL APPLICATION.