This project contains 3 studies. While bipolar disorder (BD) would increase substance use and worsen cognitive decline, polygenic risk score (PRS) for BP positively correlated with educational attainment and creativity, both were protective factors of cognitive decline. Study 1 aims to explore the role of PRS of BD and its pathways on midlife cognitive functions through substance use and lifestyle. Its research questions are:
-Are PRS for BD associated with cognitive decline during mid-adulthood?
-Do substance use, education attainment and creativity mediate the pathway from PRS for BD to cognitive decline during mid-adulthood?
Study 2 views midlife cognitive decline from psychosocial and behavioral factors. Quality of sleep and social life are multidimensional and modifiable, but their aspects most related to inflammation and cognitive decline are unknown. Study 2 aims to explore the dimensions of sleep quality and social engagement that are related to cognitive functions through inflammation during midlife by network analysis. Its research question is:
-What are the multivariate relationships between various dimensions of sleep quality and social engagement, PRS for Alzheimer’s disease, depressive symptoms, inflammation, and neurocognitive biomarkers in mid-adulthood, controlling for demographics?
Study 3 aims to explore gene-environment interaction. Exposure to air pollution, in particular PM2.5, is found to be linked with lower cognitive functions, but the strength of this conclusion is mixed among systematic reviews. While air pollution could reduce outdoor physical activity, walking amount could be moderated by the built environment walkability. Study 3’s research questions are:
-Do built environment in terms of walkability and air pollution affect the cognitive decline in mid-adulthood?
-Is there a moderating effect between walkability and air pollution from PRS on Alzheimer’s disease on physical activity and cognitive decline in mid-a