Project Grant F31AG099641

BRAIN HEALTH IN MIDLIFE AND LATER ADULTHOOD: RISK AND PROTECTIVE FACTORS FOR HEALTH, COGNITION, AND ALZHEIMER'S DISEASE - CARDIOVASCULAR DISEASE (CVD) AND ALZHEIMER'S DISEASE AND RELATED DEMENTIAS (ADRD) ARE TWO OF THE LEADING CAUSES OF DEATH IN THE UNITED STATES. SIMILAR RISK FACTORS ACCOUNT FOR AN ESTIMATED 70% OF CVD AND 45% OF ADRD CASES. WHILE MUCH OF PAST WORK HAS EXAMINED RISK FACTORS INDEPENDENTLY, THERE IS INTEREST IN DETERMINING HOW COMBINATIONS OF MULTIPLE MODIFIABLE RISK FACTORS RELATE TO CVD AND ADRD USING RISK SCORES AND RISK PROFILES. THE MASSACHUSETTS GENERAL HOSPITAL MCCANCE BRAIN CARE SCORE (BCS) IS A RISK SCORE THAT WAS DEVELOPED IN 2022, AND INCLUDES 12 MODIFIABLE RISK FACTORS FOR CVD AND ADRD. THE MCCANCE BCS WAS SHOWN TO PREDICT THE RISK OF DEMENTIA, STROKE, DEPRESSION, AND NEUROIMAGING MARKERS OF BRAIN HEALTH IN THE UK BIOBANK. HOWEVER, IT IS UNCLEAR WHETHER THE MCCANCE BCS PREDICTS A BROADER RANGE OF INDIVIDUAL DIFFERENCES IN AGE-RELATED CHANGES IN COGNITION AND HEALTH IN MIDDLE AGE AND LATER ADULTHOOD. OF INTEREST IS WHETHER A MODIFIED VERSION OF THE BCS DERIVED FROM TWO LARGE LONGITUDINAL DATASETS, THE MIDLIFE IN THE UNITED STATES (MIDUS) STUDY AND HEALTH AND RETIREMENT STUDY (HRS), WILL PREDICT CHANGES IN COGNITION AND HEALTH, AND CVD, COGNITIVE IMPAIRMENT AND ADRD. ALSO OF INTEREST IS WHETHER INFLAMMATION IS A MEDIATOR OF THE RELATIONSHIPS BETWEEN THE BCS AND HEALTH AND COGNITIVE OUTCOMES, AND WHETHER THERE ARE MEANINGFUL PROFILES OF THE BCS ITEMS IN RELATION TO INDIVIDUAL DIFFERENCES IN CHANGES IN COGNITION AND HEALTH, AND CVD, COGNITIVE IMPAIRMENT AND ADRD. THIS PROPOSAL FOR A TRAINING PROGRAM SEEKS TO ADAPT THE MCCANCE BCS USING COMPARABLE VARIABLES FROM MIDUS AND HRS TO: (AIM 1) EXAMINE WHETHER THE BCS PREDICTS CHANGES IN COGNITION AND PHYSICAL HEALTH AND CVD, COGNITIVE IMPAIRMENT AND ADRD AND TO CONSIDER SOCIODEMOGRAPHIC MODERATORS, (AIM 2) TEST INFLAMMATION AS A MEDIATOR OF THESE RELATIONSHIPS, AND (AIM 3) IDENTIFY RISK PROFILES MOST ASSOCIATED WITH DIFFERENTIAL CHANGES IN HEALTH AND COGNITION AND CVD, COGNITIVE IMPAIRMENT AND ADRD. (AIM 3) WILL ALSO TEST WHETHER RISK PROFILES AND THEIR RELATIONSHIPS WITH HEALTH OUTCOMES DIFFER BY AGE, SEX, AND EDUCATION. COMPLETION OF THIS WORK WILL HELP THE APPLICANT PURSUE A CAREER IN AGING RESEARCH BY PROVIDING TRAINING TO LEARN: (1) HOW TO USE LONGITUDINAL DATA FROM HRS, (2) HOW TO HARMONIZE THREE DATASETS (HRS AND MIDUS MAIN AND REFRESHER SAMPLES), (3) ANALYTIC METHODS (MPLUS), STATISTICAL TECHNIQUES (SURVIVAL ANALYSIS AND LATENT CLASS AND LATENT PROFILE ANALYSIS), AND DATA VISUALIZATIONS, AND (4) TO DEVELOP SKILLS IN SCIENCE COMMUNICATION. DR. LACHMAN WHOSE EXPERTISE IS IN LONGITUDINAL RESEARCH ON HEALTH AND COGNITION IS WELL-SUITED TO SERVE AS THE SUPERVISOR TO HELP THE APPLICANT ACHIEVE HER RESEARCH AND TRAINING GOALS. IMPORTANTLY, THIS WORK HAS THE POTENTIAL TO INFORM LIFESTYLE INTERVENTIONS TARGETING MULTIPLE MODIFIABLE BEHAVIORS TO REDUCE RISK OF DISEASE AND PROMOTE GOOD COGNITIVE AND PHYSICAL HEALTH IN MIDLIFE AND LATER LIFE.