Integrating population neuroscience and syndemics frameworks to better understand global sex and gender‐based risk in Alzheimer’s disease and related dementias

Abstract

AbstractAging populations in low‐ and middle‐income countries (LMICs) are growing more rapidly than those in high income countries (HICs). Thus, globally, the burden of Alzheimer’s disease and related dementias (ADRD) profoundly impacts LMICs, with greater burden and risk for late‐life women than men. LMICs are unable to meet diagnostic challenges with underfunded healthcare infrastructure, low numbers of clinicians with training and expertise in ADRD, and a lack of culturally and linguistically sensitive screening assessments. Emerging social and societal factors that are important risk and protective factors for later life ADRD and are differentially experienced by gender/sex are relatively understudied, yet essential in LMICs. Typical samples in neuroscience studies have been small and highly selected. They have been biased toward Western, Educated, Industrialized, Rich, and Democratic (WEIRD) samples and do not apply well to target populations in LMICs. In addition, levels‐of‐analysis across social/societal and biological determinants of disease are not typically integrated, and social/societal factors such as sociocultural (e.g., culture, religion, gender norms, access to education, discrimination, social aspects of pandemics, disability), political (e.g., governments and policies; migrants and displaced persons; war and conflict; reproductive health, justice, and agency), environmental (e.g., climate change and pollution), and economic factors (e.g., poverty), and their co‐occurrence, have been minimally considered for their role and impact on ADRD. To better understand gender/sex differences in ADRD in LMICs, we review how these social and societal factors may be important to ADRD using an integrated Population Neuroscience and Syndemics framework. Population neuroscience considers the brain in context using multiple levels of analyses, a life course perspective, and tools to enhance internal and external validity, while Syndemics suggest that diseases and social conditions may cluster and interact in populations with syndemic risk factors—sociocultural, political, economic, and environmental factors which promote stress pathways. We lay out a model in which syndemic risk and protective factors contribute to or protect from stress and biological aging and ultimately ADRD risk, both directly and indirectly through physical and mental health conditions. We close with recommendations for future aging and ADRD research based on this integrated Population Neuroscience‐Syndemics of ADRD framework.