ABSTRACT The global burden of dementias continues to rise; by 2050, it is estimated that approximately 152 million people across the globe are going to be affected by dementias at a cost of 3 trillion US dollars. This is a particular issue in China as it has the world's largest population of people with dementia. Despite the incredible increase in Alzheimer's disease and cognitive dementias, very little progress has been made to prevent and successfully treat these devastating diseases. The primary reasons for the lack of progress are: 1) continued focus on single causes of disease rather than multifactorial etiologies; 2) lack of long-term follow-up data that captures environments, lifestyle behaviors, and individual susceptibility factors before, during, and after cognitive decline; and 3) insufficient attention to biological susceptibility along with dietary, lifestyle and environmental strategies. China has a larger aging population and longer life expectancy than ever before. Recent trends have led to a new phenomenon of older adults left behind when the younger generation migrates to find work. These demographic changes as well as other urbanization-related changes provide context and opportunity to address these issues. The China Health and Nutrition Survey (CHNS), an NIH- funded study of more than 10,000 individuals aged 45-80 followed over 35 years, provides high quality longitudinal data and captures the transition from traditional to Western lifestyles in parallel with urbanization and emergence of cognitive decline during the past three decades. We will use these data to generate insights that would not be obtainable in studies with short periods of follow-up in older populations that focus on single causes of cognitive decline. We propose to capitalize on the 30-year span of coverage and geographic scope of the CHNS, which provides substantial temporal and spatial variability, capturing extraordinarily rapid urbanization-related changes, biological susceptibility factors, and cognitive decline data as well as changes in individual, household and community environments. We propose data collection of an additional round in 2021, preserving the continuity of the CHNS, while adding aging-focused components (e.g., tooth loss, hearing, vision, and additional executive function tests, and in a subsample infectious and inflammatory markers, such as cytokines and viral and bacterial pathogens implicated in Alzheimer's disease) to inform understanding of the factors that lead to healthy aging versus physical and cognitive decline, and severe dementias. We will use a series of complex statistical models to identify trajectories of key risk factors and their combinations that predict or protect against early and severe cognitive decline. The impact of the proposed project is to generate an 11th wave of multipurpose data capturing long-term exposure to major urbanization-related and demographic changes, particularly within the recent 5 years, and...