Impact of Neuroinflammation on AD Occurrence: A Bi-Generational Population Study - Impact of Neuroinflammation on AD Occurrence: A Bi-Generational Population Study The Chicago Health and Aging Project (CHAP) has made several significant contributions to Alzheimer's disease and related dementias (ADRD) epidemiology for over three decades. These areas include racial disparities, prevalence and incidence of dementia trends, social, lifestyle, vascular, genetic risk factors, and neuroimaging and blood biomarkers in a large population-based community study of African Americans (AAs) and European Americans (EAs). Using the older CHAP parent and the ongoing midlife offspring cohorts, we will test several novel and innovative hypotheses on the impact of neuroinflammation on ADRD, MCI, cognitive decline, and structural MRI brain injury. By extending the awarded NIA NOSI Administrative Supplement, this intergenerational study provides significant advantages by investigating: (1) the effect of neuroinflammation amongst those with higher inflammatory cytokines and their influence on adverse cognitive outcomes; and (2) the changes in physical and cognitive activities, social engagement, and vascular risk factors in a shared family environment in the first (1993-2019) and second (2021-2027) phases of the study, which spans three decades in a population-based community study. To address this scientific area of research, we propose to conduct a population-based community study of 4,000 older CHAP parents with two population cognitive assessments and detailed clinical evaluations for ADRD in 1,200 participants with the following specific aims: (1) Estimate the 2020 US census demographic adjusted overall and demographic-specific (age, race/ethnicity, and gender) prevalence and incidence of ADRD, MCI, and dementia likelihood and test whether the prevalence and incidence have changed over the three decades of the study (1993-2012 & 2022-2027). Additionally, test whether the 5-year risk of ADRD among high-risk AA parents has high-risk offspring compared to EAs; (2) Examine the change in physical and cognitive activities, social engagement, BMI, and hypertension in the two phases of the study (1993-2012) and (2022-2027) and the impact of these changes on the risk of ADRD, MCI, cognitive decline, and MRI brain injury. Furthermore, test whether these associations are higher by age, sex (males vs. females), and among AA parents and offspring compared to EA parents and offspring; (3) Test whether participants with elevated concentrations of inflammatory cytokines and serology antibodies among those with higher vascular risk factors have a higher risk of ADRD, MCI, cognitive decline, and structural MRI brain injury. Finally, test whether these associations are higher among AA parents and offspring compared to EAs. This proposal has an enormous impact on prevention programs by developing strategies and therapeutic studies on understanding neuroinflammatory pathways on population health across generations from midlife to late life in socially disadvantaged populations.
