As global life expectancy rises, the demographic shift toward an aging population presents challenges on a worldwide scale. The World Health Organization (WHO) emphasized in its 2015 Global Report on Ageing and Health that the objective of Healthy Ageing is to facilitate individuals in “developing and sustaining the functional capacities essential for health in old age.” And the healthy cognitive function stands as a pivotal objective within the WHO Public Health Framework for Healthy Ageing. In the context of an aging population, the impact of cognitive decline on public health is of increasing concern. Cognitive decline leads to an increasing burden on patients, carers, society and the healthcare system. Cognitive decline, characterized by the progressive degeneration of mental capacities such as memory, attention, and problem-solving skills, is inherent in the aging process. This decline can be associated with factors such as neurodegeneration, vascular issues, brain trauma, medical conditions, and gene expressions. A comprehensive understanding of the underlying causes is imperative for the development of effective interventions and treatments.
The primary objective of our research is to detect the environmental, socioeconomic, and genetic factors contributing to cognitive decline and to comprehensively understand the mechanisms through which these factors exert their impact on cognitive deterioration. Moreover, we aim to characterize precisely delineate specific threshold in the aging process above which cognitive function experiences a significant decline for a heterogeneous population.
We also aim to understand the causal relationship between cognitive decline and other related phenotypes based on UK Biobank data. To achieve this, genetic variants could be leveraged as instrumental variables to reduce the unobserved confounding in the cohort study. However, genetic variants are subject to the pleiotropic effects, making them possibly invalid instruments. We will develop new methods for causal inference, which can account for the pleiotropic effects of genotypes. These developments could contribute on weakening the untestable model assumptions and generate more reliable causal discoveries in real applications.
We request to the duration of our project for 36 months to get publications and accomplishments using the UK Biobank data. The duration includes the time for processing and preparing all imputation genotypes, phenotypes, data applications, statistical analyses, and manuscripts writing for submission to publications.