INTRODUCTION: The projected growth of Alzheimer's disease (AD) and AD-related dementia (ADRD) cases by midcentury has expanded the research field and impelled new lines of inquiry into structural and social determinants of health (S/SDOH) as fundamental drivers of disparities in AD/ADRD. METHODS: In this review, we employ Bronfenbrenner's ecological systems theory as a framework to posit how S/SDOH impact AD/ADRD risk and outcomes. RESULTS: Bronfenbrenner defined the "macrosystem" as the realm of power (structural) systems that drive S/SDOH and that are the root cause of health disparities. These root causes have been discussed little to date in relation to AD/ADRD, and thus, macrosystem influences, such as racism, classism, sexism, and homophobia, are the emphasis in this paper. DISCUSSION: Under Bronfenbrenner's macrosystem framework, we highlight key quantitative and qualitative studies linking S/SDOH with AD/ADRD, identify scientific gaps in the literature, and propose guidance for future research. HIGHLIGHTS: Ecological systems theory links structural/social determinants to AD/ADRD. Structural/social determinants accrue and interact over the life course to impact AD/ADRD. Macrosystem is made up of societal norms, beliefs, values, and practices (e.g., laws). Most macro-level determinants have been understudied in the AD/ADRD literature.

2nd Faculty of Medicine Charles University Prague Czech Republic

Applied Health Economics and Outcomes Research and Health Policy Jefferson College of Population Health Thomas Jefferson University Philadelphia Pennsylvania USA

Bethesda Maryland USA

Center for Innovation in Healthy and Resilient Aging Arizona State University Phoenix Arizona USA

Center for Optimal Aging Marymount University Arlington Virginia USA

Clinical Research and Leadership Neurology The George Washington University Washington D C USA

Comprehensive Center for Brain Health University of Miami Miller School of Medicine Miami Florida USA

Department of Clinical Research and Leadership School of Medicine and Health Sciences The George Washington University Washington D C USA

Department of Neurology Columbia University New York New York USA

Department of Neurology Memory and Aging Center University of California San Francisco California USA

Department of Neurology Memory and Aging Center University of California San Francisco Global Brain Health Institute University of California San Francisco and Trinity College Dublin San Francisco California USA

Department of Neurology Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University Medical Center New York New York USA

Department of Neurology Washington University School of Medicine St Louis Missouri USA

Department of Psychology Faculty of Humanities University of Johannesburg South Africa

Department of Public Health Sciences University of California Davis School of Medicine Davis California USA

Department of Social and Behavioral Health School of Public Health University of Nevada Las Vegas Nevada USA

Departments of Epidemiology and Sociomedical Sciences Mailman School of Public Health Columbia University New York New York USA

Departments of Psychiatry Population Health and Neurology New York University Grossman School of Medicine New York New York USA

Edson College of Nursing and Health Innovation Arizona State University Phoenix Arizona USA

Institute of Public Health Washington University in St Louis St Louis Missouri USA

MA Department of Psychiatry Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USA

MPH Department of Epidemiology and Biostatistics Temple University Philadelphia Pennsylvania USA

Nell Hodgson Woodruff School of Nursing Emory University Atlanta Georgia USA

NIA Funded Network on Life Course and Health Dynamics and Disparities University of Southern California Los Angeles California USA

Rush Alzheimer's Disease Center and the Department of Psychiatry and Behavioral Sciences Rush University Medical Center Chicago Illinois USA

School of Nursing Alzheimer's Disease Research Center and School of Medicine and Public Health University of Wisconsin Madison Madison Wisconsin USA

School of Nursing Johns Hopkins University Baltimore Maryland USA

School of Public and Community Health Sciences University of Montana Missoula Montana USA

The Saul R Korey Department of Neurology Albert Einstein College of Medicine Bronx New York New York USA

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