Approved Research

Gene-environment interaction of modifiable risk factors for cognitive decline and their associations with structural and functional MRI in the UK Biobank

Lay summary

Due to ageing of the global populations, chronic disorders including dementia are becoming increasingly frequent. In 2015, 47 million people world-wide were affected, a number expected to double within the next twenty years. Alzheimer's disease is the most frequent cause of dementia in older individuals, but accumulating damage of blood vessels in the brain and other causes contribute to the individual risk. Worsening of memory and thinking are among the earliest symptoms in Alzheimer's disease, and other brain functions such as orientation, language and problem solving become impaired increasingly as the disease progresses. Brain magnetic resonance imaging (MRI) is a reliable method to detect shrinkage of brain regions and disruption of brain networks related to those symptoms.

A recent analysis on the entire scientific literature on potentially modifiable risk determinants for dementia resulted in a list of twelve factors, explaining 40% of the worldwide dementia cases, including alcohol abuse, head injury, air pollution, low education, hypertension, hearing impairment, smoking, obesity, depression, physical inactivity and few social contacts. The UK Biobank includes a rich dataset of information from questionnaires, medical assessments, blood laboratory measures, with the unique opportunity to study the influence of lifestyle choices and genetic risk for dementia in a large population.

Our main objective is to explore in the UK Biobank cohort the relationship of the mentioned twelve dementia risk factors with brain structure and function as well as with known Alzheimer's disease risk genes. We will assess how the risk factors influence changes of brain volume and network function and cognitive performance over time. Furthermore, we will aim to identify interactions between genes and lifestyle factors to understand the heritability of dementia risk better.  The planned study will provide robust new data on the biological underpinning of lifestyle-related dementia risk, supporting the development of better treatment and prevention strategies.