| Title: | A phenotype-wide and omics analyses of social and environmental exposomes, sleep-architectures, aging related multimorbidity with pre-clinical brain pathological changes and incidence of dementia |
| Lead Institution: | West China Fourth Hospital, Sichuan University |
| Principal investigator: |
Application 203528
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About
With the global rise in the elderly population, there has been a notable increase in the occurrence of diseases and mortality rates, with dementia being a major contributor. Dementia not only leads to functional impairments but also reduces life expectancy, making it a critical concern for public health. However, most existing studies on dementia primarily rely on epidemiological analyses, lacking comprehensive pre-clinical brain image features and omics-based analyses that are crucial for understanding the development of early-stage dementia. Additionally, although previous research has explored risk factors associated with dementia, such as diet, physical activity, sleep quality, metabolites, air pollution, and living in greener environments, no systematic studies have been conducted to assess the combined effect of these factors. Meanwhile, the precise mechanism by which these factors influence the risk of dementia, particularly the pre-clinical brain pathological changes, remains largely unclear, making early-stage dementia development elusive. Moreover, while incident multimorbidity, including conditions like obesity, stroke, depression, and sleep disturbances, has been reported to be associated with dementia, validating these associations requires large-scale prospective studies. Understanding the onset of dementia is of clinical significance as it can aid in prevention and delay the progression of the disease. Therefore, our project aims to (1) examine the independent and joint associations of social, dietary, behavioral, and environmental exposomes with dementia-related brain changes and incidence using prospective cohort studies; (2) uncover the underlying mechanisms of exposomes on dementia risks through omics and genetic analysis; (3) estimate the temporal patterns of multimorbidity leading to dementia transmission, highlighting the relationships and potential mechanisms among exposomes, multimorbidity, and dementia risks. To achieve these objectives, we will conduct a prospective observational analysis, genome-wide association analysis, phenome-wide association analysis, and mendelian randomization analysis. Additionally, a series of secondary analyses will be performed using data from the UK Biobank. Our plan is to begin the analyses as soon as the data become available and aim to complete the project within 36 months, including manuscript preparation for review by authors. We hope that our study will provide a comprehensive understanding of the associations between exposomes, sleep architectures, aging-related multimorbidity, and pre-clinical brain pathological changes. Additionally, we anticipate identifying novel biological pathways and potential preventive targets for improving dementia prevention. Our project's objectives align with the goals of the UK Biobank, which is dedicated to enhancing the prevention, diagnosis, and treatment of various serious and life-threatening illnesses, including dementia.1 Publication
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 15341 | How does biological age acceleration mediate the associations of obesity with cardiovascular disease? Evidence from international multi-cohort studies | Lin Hu (+9) | 2025 | Cardiovascular Diabetology |
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