Approved Research

Investigating the effect of APOE4 presence and non-modifiable risk factors on the benefits of physical activity for dementia incidence and brain volume

Lay summary

The risk of getting dementia is a combination of genetics and the environment. Generally, leading a more physically active lifestyle leads to a lower chance of being diagnosed with dementia. However, the benefits of physical activity may vary according to genetics, ethnicity, and sex. Variations in the APOE gene are one of the most important risk factors for dementia. Presence of the e4 variant of the APOE gene increases dementia risk. Some evidence suggests that those with the e4 variant benefit more from living healthier lifestyles, including completing more physical activity; though current findings are inconclusive, and further investigation is required. The relationship between physical activity and dementia risk is not present across all ethnicities; the amount of moderate-to-vigorous physical activity completed by black people is unrelated to their risk of dementia, but the relationship between physical activity and dementia incidence in the South Asian community, the second largest in Great Britain, is unclear using objectively measured physical activity data. In addition to this, women have a higher risk of dementia than men, but it is unclear whether the protective benefits of physical activity are equal in both sexes.

Changes in the brain can indicate a reduction in brain health; but physical activity typically prolongs reductions in brain and ventricular volume associated with aging. Differences in the relationship between physical activity and brain volume may occur across APOE e4 status, sex, and ethnicity; but this requires deeper investigation.

Therefore, the aim of this project is to better understand how ethnicity, sex, and genetic predisposition for dementia, impact the relationship between physical activity and dementia incidence and brain volume. This project is also aiming to explore potential interactions between these genetic factors; and if these interactions influence the association between physical activity and dementia risk and brain volume.

This project should take no longer than 36 months.

This project is designed with public health in mind. Ethnicity, sex, and their possible interaction with APOE gene variants, are an under-explored area of research, and may have important public health implications. Better understanding of the nuances of the relationship between environmental and genetic risk factors for dementia are important, in order to develop prevention strategies for dementia that are tailored to the individual. If environmental risk factors can be optimised, rates of dementia may also be reduced, decreasing burden on individuals and healthcare systems.

Scope extension:

Do individuals with APOE e4 benefit more from physical activity in the reduction of dementia risk?

Do individuals with APOE e4 benefit more from physical activity when examining changes in total brain volume and ventricular volume?

Do ethnicity and sex influence the relationship between physical activity and dementia incidence?

Do ethnicity and sex influence the relationship between physical activity and total brain volume and ventricular volume?

Are there interactions between APOE status, sex, and ethnicity, and physical activity and dementia risk?

The aim of this project is to explore the interaction between APOE genotype, ethnicity, sex and physical activity in the incidence of dementia and brain volume.

Do ethnicity, sex and APOE e4 influence the relationship between physical activity and cognitive ability?