Impaired spatial navigation signals early Alzheimer’s risk

People at risk of Alzheimer’s disease have impaired spatial navigation before problems with other cognitive functions, including memory, finds a new study led by UCL researchers.

The research, published in Alzheimer & Dementia: The Journal of the Alzheimer’s Associationused virtual reality to test the spatial navigation of 100 asymptomatic middle-aged adults, aged 43–66 years, from the PREVENT-Dementia prospective cohort study.

Participants had a genetic or physiological risk for Alzheimer’s disease, either because of a gene (the APOE-ε4 allele) that puts them at risk for the condition, a family history of Alzheimer’s disease, or lifestyle risk factors such as low levels of physical activity. . Most notably, these participants were about 25 years younger than the estimated age of dementia onset.

Led by Professor Dennis Chan, the study used a test designed by Dr Andrea Castegnaro and Professor Neil Burgess (all UCL Institute of Cognitive Neuroscience), which asked participants to navigate a virtual environment wearing a VR headset.

The researchers found that people at higher risk of developing Alzheimer’s disease, regardless of the risk factor, were selectively impaired on the VR navigation task, without a corresponding impairment on other cognitive tests. The authors say their findings suggest that impairments in spatial navigation may begin to develop years, or even decades, before any other symptoms appear.

The first author, Dr. Coco Newton (UCL Institute of Cognitive Neuroscience), who carried out the work at the University of Cambridge, said: “Our results showed that this type of change in navigational behavior may represent the earliest diagnostic signal in the Alzheimer’s disease continuum. – when people move from being problem-free to developing disease.”

The researchers also found that there was a marked gender difference in how the participants performed, with impairment seen in men rather than women.

We are now taking these findings forward to develop a diagnostic clinical decision support tool for the NHS over the coming years, which is a whole new way of approaching diagnostics and will hopefully help people get a more timely and accurate diagnosis.

This is especially important with the advent of anti-amyloid therapies for Alzheimer’s disease, which are considered more effective in the early stages of the disease.

It also highlights the need for further study of the differential vulnerability of men and women to Alzheimer’s disease and the importance of considering gender in both diagnosis and future treatment.”

Dr. Coco Newton, First Author

Professor Chan said: “We are excited by these findings for two main reasons: First, they improve detection of the clinical onset of Alzheimer’s disease, which is critical for early implementation of treatments.

“Second, the VR navigation test builds on our knowledge of the spatial properties of cells in the temporal lobe of the brain, and the application of cellular neuroscience to clinical populations helps bridge the gap in understanding how disease at the neuronal level can lead to the clinic This knowledge gap currently represents one of the greatest barriers to progress in Alzheimer’s research.”

The research was carried out in collaboration with the University of Cambridge, with joint funding from the Alzheimer’s Society and an MSD research grant.

Dr Richard Oakley, Deputy Director of Research and Innovation at the Alzheimer’s Society, said: “One in three people born today will develop dementia and early and accurate diagnosis of the diseases that cause the condition is vital for people to access the right support, plan for the future and receive appropriate treatment.

“The very early symptoms of dementia can be subtle and difficult to detect, but problems with navigation are thought to be some of the first changes in Alzheimer’s disease.

“This study was funded in part by the Alzheimer’s Society and used virtual reality technology to show that a healthy person’s navigation skills are linked to dementia risk, based on genetic and environmental factors.

“This innovative technology is far from being a diagnostic test, but it provides more evidence for the role of navigation skills as an early sign of Alzheimer’s disease. More work is needed to develop this technology, but it will be exciting to see how it research may provide a way to detect disease-related changes early and help people living with dementia in the future.”