We are only beginning to clarify the ways the COVID-19 pandemic has resulted in substantial changes to American neighborhoods. There has been an excess of permanent business closures, particularly among small neighborhood businesses most vulnerable to social distancing, such as local barbershops and nail salons. COVID-19 outbreaks in late September 2021 caused 2,000 neighborhood schools to close for an average of six days in 39 states.

A burgeoning body of research has tried to understand the forces driving these trends, focusing on infectious disease transmission at the individual level or economic models at the business level. What is not considered is the context in which these changes are taking place. By context, we mean the neighborhood community environment that holds the opportunities, restrictions, risks, and flexibility for post-pandemic growth. The community environment includes:

1. Job opportunities in business sectors robust to social distancing;
2. Comprehensive broadband internet access to facilitate telemedicine, online schooling, remote work, and online grocery shopping;
3. Parks and walkable streets to facilitate socially distanced physical activity and social interaction to mitigate social isolation brought on by the pandemic; and
4. The provision of medical care through the availability of alternate health care providers and pharmacies.

Access to these neighborhood resources is not equally distributed across America, reinforcing risk for vulnerable populations, including older adults, children and adolescents, racial/ethnic minorities, and those in rural areas. However, a lack of national, standardized, longitudinal metrics of the local neighborhood environment has hindered the ability to identify which communities are most vulnerable to the immediate and longer-term consequences of the pandemic for a host of behavioral, psychological, social, and economic outcomes.

To address this limitation in the nation’s data infrastructure, we will augment, curate and disseminate data from our National Neighborhood Data Archive (NaNDA). This dataset includes a wealth of physical, social and economic characteristics of the local neighborhood across the United States (e.g., racial segregation, business density, environmental hazards, broadband internet access, and healthcare availability), in the years both before and since the pandemic. We will participate with the Consortium on Social, Behavioral, and Economic Research on COVID-19 to integrate, share, and analyze spatially referenced neighborhood data that can be readily linked to existing survey data, cohort studies, or electronic health records at various levels of geography. We will work with the COVID-19 Consortium Coordination Center to identify and create key neighborhood metrics that are priorities for research teams in the Consortium, including a set of common data elements (CDEs) on the social, behavioral and economic indicators of the COVID-19 pandemic at the neighborhood level. We will also develop new metrics of longitudinal neighborhood change in the decades preceding the pandemic, which can inform community risk and resilience since the pandemic.

The process of aging often leads to increased disability, loss of physical functioning, cognitive decline, and development of multiple chronic diseases. One critical driver of this process is senescence of the immune system, or immunosenescence, which is known to be associated with chronic inflammation. However, emerging evidence also points to immune dysfunction resulting from continual assault on the immune system by multiple persistent infections. Together, these infections and resulting immune dysfunction set in motion a cascade of events leading to accelerated immunosenescence. Accelerated immunosenescence may then be a driver of health disparities later in life. New research suggests disparities in immune dysfunction across the life course can be linked to social disadvantage extending back to childhood. A critical knowledge gap is how early-life social disadvantage accelerates immunosenescence through immune dysfunction. The objective of the proposed research is to explore pathogen burden as a critical mediator in the pathway from childhood social disadvantage to accelerated aging, as measured by inflammation and immune dysfunction.

The first objective of this project is to define the association between childhood social disadvantage and pathogen burden across the life course. Childhood social disadvantage is defined by both low socioeconomic status and experiences of stressors, such as parental death or physical abuse, before 18 years of age. Individuals experiencing higher levels of social disadvantage in childhood should have increased levels of pathogen burden throughout the life course.

Defining the association between pathogen burden and immune system dysfunction and inflammationis the second objective of this project. Grace Noppert will do this first by testing the association between pathogen burden and inflammation in existing cohort studies and then test the association between pathogen burden and immune dysfunction longitudinally.

The third objective is to examine the degree to which the association between childhood social disadvantage and inflammation/immune dysfunction is mediated by pathogen burden .

At its conclusion, this project will extend our knowledge of the aging process early in the life course, specifically how childhood social disadvantage can induce accelerated aging through the mechanism of pathogen burden and amplify disparities in aging. Ultimately, this will work will inform our understanding of modifiable processes that cause disease, disability, and mortality across the life course.

While risk factors for cognitive decline and Alzheimer ’s disease and related dementias (ADRD) have been widely studied, there is still much unknown about the biological pathways that lead to ADRD. This project seeks to improve our understanding of the pathophysiology of cognitive decline and ADRD by examining the role of peripheral immunosenescence in these processes. A major gap in existing research is a lack of longitudinal studies that can establish an etiologic link between peripheral immunosenescence and development of incident ADRD. In addition, there are few population-based studies examining these processes in U.S. representative samples. Population-based studies can evaluate whether clinical findings among ADRD patients are generalizable to the broader population as well as examine the role of social determinants in these processes. Despite consistently observed social inequalities in ADRD, including based on race/ethnicity, sex/gender, and socioeconomic status, we do not yet understand the pathways by which social disadvantage lead to ADRD, limiting population-wide ADRD prevention strategies. Our long-term goal is to elucidate the role of population immunity in predicting ADRD. Our objective for this research is to evaluate the relationship between peripheral immunosenescence and domain-specific cognitive function, decline, and ADRD diagnoses in a nationally representative sample of older US adults, and, to examine the extent to which immunosenescence explains social inequalities in cognitive function, decline, and ADRD. Our central hypothesis is that immunosenescence, characterized by an increased number of senescent immune cells (e.g., CD8+CD45RA-, CD4+CD45RA-) and elevated inflammatory cytokines (C-Reactive Protein (CRP), interleukin (IL)-6, TNF-alpha) will be associated with worse cognitive outcomes, and that immunosenescence will partially explain some of the social inequalities in cognitive outcomes. Our rationale is that immunosenescence may be an important early risk factor for ADRD, potentially representing a biological mechanism explaining population heterogeneity and inequalities in ADRD risk. To investigate these relationships, we will pursue three specific aims:

1. Determine the association between peripheral immunosenescence and cognitive function and decline in the Health and Retirement Study (HRS);
2. Determine the association between peripheral immunosenescence and incident ADRD measured both by HRS cognitive assessment and linked Medicare claim data; and
3. Determine the extent to which immunosenescence explains social inequalities in cognitive function, decline, and ADRD.

This project is the first large-scale population-based study of immunity and cognition. It will yield critical insights to our understanding of the pathophysiology of cognitive decline and ADRD, and inequalities in these processes. This project is significant because the results could point to new diagnostic tools able to discern profiles of immunosenescence predictive of ADRD in the peripheral blood.

The intergenerational persistence of poor health and poverty and the quest to understand underlying processes underscore the importance of rich multigenerational data. Very few existing datasets contain comprehensive information on social, environmental, and biological factors over the life course and across generations; lack of such data has seriously limited attempts to identify the processes shaping health disparities, economic inequalities, and causal linkages between the two. The Fragile Families and Child Wellbeing Study (FF) is the longest running birth-cohort study in the U.S The study is based on a national probability sample and follows parents — both mothers and fathers — and their children who were born in 1998-2000. Based on birth statistics, the children in FF are now having children of their own. We are expanding the FF study by conducting a perinatal survey on the health of this third generation of children, early parenthood experiences of the second generation. We are examining the characteristics of households and families into which the third generation are born, as well as collecting biological specimens from the new children and their non-FF parents. The augmented data will have many unique and valuable features, including:

1. extensive data on three generations of families: children, parents, and grandparents;
2. data on siblings and half-siblings (in the third generation);
3. three generations of exposures and genetic and epigenetic data;
4. genetic data on trios (third generation children and both of their parents); and
5. comprehensive data on perinatal health (pre-pregnancy, prenatal, delivery, neonatal, and postpartum factors including breastfeeding and postpartum depression) and circumstances in the second and third generations.

The Fragile Families Third Generation study will facilitate novel and important analyses of intergenerational transmission of health, intergenerational relationships within families, and gene-environment effects on health. It will also provide an essential foundation for future third generation data collection at subsequent developmental transitions including school readiness and emerging adulthood.

By 2030, 8.5 million Americans will be diagnosed with Alzheimer’s disease and related dementias (ADRD); yet because socioeconomically disadvantaged populations are underrepresented in ADRD research, the extent of ADRD disparities by socioeconomic factors are poorly understood. Food insecurity, a condition of limited food availability due to insufficient resources, is an understudied dimension of socioeconomic disadvantage among older adults. Food insecurity has increased 128% among older adults since 2001, and has been associated with lower cognitive function in limited cross-sectional studies.

The lack of rigorous research investigating the effect of food insecurity on cognitive impairment and ADRD risk is a widely acknowledged gap in the health disparities and ADRD literature. This represents a major missed opportunity to better understand how a key social determinant of health can be influence cognitive health in later life.

The overall objective for this research is to understand the longitudinal and dynamic effects of food insecurity on cognitive impairment and ADRD risk in older adults. Food insecurity is both preventable and reversible; therefore, the rationale for this project is that establishing food insecurity as a risk factor for cognitive impairment and ADRD risk will inform public health strategies to address the dual burden of food insecurity and ADRD among older adults.

Our specific aims are: 1) evaluate the dynamic effects of food insecurity in adulthood on ADRD risk; 2) identify the longitudinal effects of food insecurity on trajectories of cognitive impairment; and 3) examine heterogeneity by sociodemographic characteristics and diet quality on the effects of food insecurity on cognitive impairment and ADRD risk. To achieve the proposed aims, this project will leverage data from two well-established cohort studies: 1) the Panel Study of Income Dynamics (PSID), the longest running nationally representative household panel survey, and 2) the Health and Retirement Study (HRS), the leading nationally representative study on aging.

This project will be the first to rigorously examine the effects of food insecurity on ADRD risk among older adults. By leveraging data from two longitudinal and nationally representative studies, this project will provide a complementary and comprehensive understanding of the effects of food insecurity on cognitive impairment and ADRD risk. These results will have significant clinical, public health, and policy implications by identifying modifiable risk factors to promote healthy cognitive aging and improve quality of life, particularly among socioeconomically disadvantaged populations.

This project will review the literature on methods for estimating racial disparities in economic outcomes with a specific focus on how controls for other factors (e.g., education) are or are not included in such analyses. These methods would be compared with those in health services research, where relative consensus on such methods reflects the recommendations of a 2003 Institute of Medicine Panel on racial disparities in health care. The resulting paper would include simple empirical examples and guidance for applied researchers.

Racial inequalities in healthy aging have been well-documented. Compared to White Americans, Black Americans experience illness and death at early ages and show steeper age-related declines in health. Our neighborhoods, as the site of where we live, learn, play, and pray, may serve as a powerful source of these racial inequalities. Racial residential segregation (which is the sorting of different racial groups into different neighborhoods through historical and current discriminatory policies and practices) has resulted in a racially unequal American neighborhood landscape. Neighborhoods with mostly Black residents experience more poverty, civic and commercial disinvestment, and more exposure to environmental hazards compared to neighborhoods with mostly White residents. While more researchers are documenting the role of neighborhoods in health inequalities, we may actually be underestimating the true impact of neighborhood context, because we often focus on specific health outcomes, such as cardiovascular disease or diabetes. However, there are likely shared biological mechanisms within the body that drive many of these diseases — and one such mechanism may be changes to our genomic structure, called epigenomics. While our genes do not change, the environment can have an impact on whether our genes are actually expressed. We will determine whether the accumulation of adulthood lived experience in racially-segregated neighborhoods is related to epigenomic patterns called DNA methylation. We will also specifically determine whether the accumulation of adulthood exposure to neighborhood industrial air pollution and disadvantage together are related to these patterns of DNA methylation. Finally, we will determine whether the DNA methylation patterns we see are related to racial inequalities in healthy aging. We hypothesize that racially-segregation Black neighborhoods, with their greater levels of industrial air pollution and social disadvantage, will be related to the types of patterns in DNA methylation that have been shown to be related to chronic diseases in molecular studies. In fact, we further hypothesize that these patterns in DNA methylation will be related to racial inequalities in cognitive function and the number of chronic diseases one has had. Clarifying the role of neighborhood context in racial inequalities in healthy aging is critical, as neighborhoods are not naturally-occurring. They develop and change through policies and are amenable to intervention. Identifying the role of DNA methylation that likely underlies many chronic diseases, will clarify the importance of neighborhoods and point to potential effective interventions.

The Panel Study of Income Dynamics (PSID) is a longitudinal survey of a nationally-representative sample of U.S. families that began in 1968. With data collected on the same families and their descendants for 39 waves over 47 years (as of 2015), the PSID can justifiably be considered a cornerstone for empirical social science research in the U.S. Through its long-term measurement of economic and social wellbeing, the study has inspired researchers to investigate the dynamics of economic, social, demographic, and health processes and their interrelationships. NICHD has co-funded the collection of the biennial Core PSID interview for all seven waves from 2003 to 2015. This project will build upon this investment in the next five-year cycle through the following specific aims: (1) screen and recruit a new immigrant refresher sample in 2016 and 2017, comprising approximately 750 immigrant households that migrated to the U.S. after 1997 (when PSID last added an immigrant refresher), and interview these families for two rounds of the Core PSID survey in 2017 and 2019; and (2) collect data from all other PSID respondents on three modules — family dynamics, fertility and newborns, and education — from two rounds of the Core PSID survey in 2017 and 2019, covering approximately 9,850 households in 2017 and 10,244 households in 2019. These data will be cleaned, documented, and distributed free of charge through the PSID Online Data Center, which provides customized extracts and codebooks. In addition, continuing outreach and support will be provided to established and new data users. This project will make several major contributions. By screening and recruiting a new immigrant refresher sample into PSID, this project will enhance the representativeness of PSID and the generalizability of results of studies using these data — now and into the future. The ongoing collection of data on family dynamics, children, and education will maintain PSID as the only long-term panel representative of the full U.S. population that can be used to study these topics over the lifecourse, across generations, and over time.