ABSTRACT The NIA has called for social science and community-based studies to clarify risk and protective factors for Alzheimer's disease and related dementias (ADRD), particularly among racial minorities who are disproportionately affected. Place, including both neighborhood of residence and region/state of birth, has consistently been correlated with ADRD, stroke, and impaired cognitive function. Yet it is unclear whether modifiable mechanisms explain this association, or whether the association is merely due to the selection of unhealthy individuals into poor regions. The goal of this study is to produce the first quasi-experimental evidence to understand the influence of neighborhood socioeconomic deprivation on ADRD and its vascular risk factors. We take advantage of a unique natural experiment, overcoming methodological challenges in the previous literature on neighborhood effects on ADRD. From 1986 to 1998, the Danish government actively dispersed roughly 76,000 incoming refugees across the country in a nearly randomized (“quasi-random”) fashion to avoid over-crowding in major cities. This cohort includes nearly 12,000 individuals who lived until at least age 60 in Denmark during the 30-year follow-up. Over 90% of families agreed to participate in the program, creating a natural experiment in which these individuals were quasi-randomly assigned to neighborhoods with different levels of deprivation. We will employ unique data spanning over 30 years from Denmark's population and clinical registers, which provide data on sociodemographics, clinical encounters, and prescriptions for all Danish residents. We identify cases of ADRD and its vascular risk factors among this racially diverse cohort via validated techniques using ICD codes and prescription data in clinical registers. We have successfully linked these registers to detailed geocoded data sources on eight measures of neighborhood socioeconomic deprivation. In Aim 1, our goal is to test the hypothesis that neighborhood deprivation increases the incidence of ADRD later in life. In Aim 2, we will examine the effects of neighborhood deprivation on vascular risk factors for ADRD, including highly prevalent conditions that occur across the life course. In Aim 3, we will identify vulnerable subgroups whose development of ADRD and vascular risk factors differs in response to neighborhood deprivation, taking advantage of the large sample size and complete register data available on all subjects. We will employ both hypothesis-driven and hypothesis-generating statistical techniques, including innovative machine learning methods that allow for more complex and robust subgroup identification. This will enable future interventions to be tailored to the most vulnerable individuals. Overall, the expected outcome of this research is to produce rigorous evidence on the effects of neighborhood characteristics on ADRD and vascular risk factors, overcoming the methodological challenges in previous work. This will directly inform the development of clinical, community, and policy strategies to address the neighborhood determinants of ADRD among vulnerable populations who are most at-risk.

PROJECT NARRATIVE The goal of this research is to examine the effects of neighborhood deprivation on Alzheimer's dementia and its vascular risk factors. We will examine the association of specific neighborhood characteristics with Alzheimer's and its risk factors, and we will assess whether specific subgroups may be more vulnerable to neighborhood deprivation. This will inform the development of interventions to address the neighborhood factors that affect Alzheimer's disease.