Impact of Neuroinflammation on AD Occurrence: A Bi-Generational Population Study - Modified Project Summary/Abstract Section The Chicago Health and Aging Project (CHAP) has made several significant contributions to the epidemiology of Alzheimer's disease and related dementias (ADRD) for over three decades. These contributions span population health, trends in the prevalence and incidence of dementia, social, lifestyle, vascular, and genetic risk factors, and neuroimaging and blood biomarkers in a large population-based community study of older adults. Using the older CHAP parent cohort and the ongoing midlife offspring cohorts, we will test several novel 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 among those with higher inflammatory cytokines and its influence on adverse cognitive outcomes; and (2) changes in physical and cognitive activities, social engagement, and vascular risk factors in a shared family environment across the first (1993-2019) and second (2021-2027) phases of the study, which spans three decades in a community setting. To address this scientific area of research, we propose to evaluate 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 (e.g., age and other key demographic factors) 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 parents translates to high-risk offspring across pre-specified demographic strata, consistent with NIH inclusion policy and available sample size; (2) Examine changes 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 vary across pre-specified demographic strata as supported by sample size; (3) Test whether participants with elevated concentrations of inflammatory cytokines and serologic 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 differ across pre-specified demographic strata, as supported by sample size. This proposal has an enormous impact on prevention programs by informing prevention strategies and future therapeutic studies to understand neuroinflammatory pathways and their effects on population health across generations from midlife to late life among participants with higher immune, vascular, or ADRD risk profiles, examined within pre-specified demographic strata.
