Universities to explore specific genetic variant known to increase dementia risk

The researchers – from Cardiff, Bristol and Oxford Universities – are combining their expertise to study how patterns of brain structure and activity in early adulthood might be linked to increased risk of dementia in later life.

Dementia costs the UK economy an estimated £24 billion annually. If research can identify methods to delay the start of dementia by five years, this cost could be halved.

Working with Bristol University’s unique birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC), they will ask whether healthy adults with APOE-e4, a genetic variant associated with a greater risk of Alzheimer’s disease, show altered patterns of brain activity and connectivity in key brain circuits involved in spatial navigation and memory.

Using powerful new scanners recently installed at Cardiff University’s Brain Research Imaging Centre (CUBRIC) the researchers are able to assess brain structure and function in unprecedented levels of detail.

Previous research by the team has demonstrated that carriers of APOE-e4 show specific differences in brain activity (compared to non-carriers) when they have to tell apart or remember different views of a scene or spatial environment.

These changes are seen in the same brain regions affected early on in Alzheimer’s disease. By applying these sensitive cognitive tests in ALSPAC participants, the researchers will be able to ask how profiles of physical and mental activity, from birth to young adulthood, affects APOE-e4’s influence on brain activity during these tasks.

Principal Investigator of the study, Professor Kim Graham, School of Psychology, said: “Understanding how risk factors for dementia lead to later life memory loss is critical to developing new therapies and preventative approaches for dementia.

“By collaborating with Bristol and Oxford Universities, and using new state-of-the-art neuroimaging in a unique birth cohort, we hope to understand the ways in which brain activity and structure is influenced by APOE-e4.

“This information will generate sensitive cognitive tests and markers of brain function able to identify individuals at increased risk for dementia many years prior to the onset of memory difficulties.”

Co-Principal Investigator, Clare Mackay, from Oxford University, added: “We increasingly recognize that to tackle complex diseases such as dementia we must pool expertise and resources. As partners in the MRC’s Dementia’s Platform UK the Cardiff-Oxford-Bristol team now have an opportunity to develop a clearer understanding of why some people are at greater risk of developing dementia.”

Executive Director of ALSPAC, Lynn Molloy, commented: “ALSPAC is delighted to be collaborating with Professor Graham and colleagues on this exciting new study.

“This remarkable, intensely studied group of study participants are now entering their mid-twenties and this study will provide new insights into how brain changes at this age might be inked to increased dementia in later life.”