Researchers at the German Centre for Neurodegenerative Diseases (DZNE) have discovered that people at higher risk of developing Alzheimer’s disease may struggle with spatial orientation, even when their memory seems normal in standard tests. In a study of just over 100 older adults, participants were asked to find their position in a virtual environment. Those who reported subjective cognitive decline (SCD)—a condition where individuals feel their memory is worsening despite normal test results—performed worse in orientation tasks compared with healthy controls. These findings, published in Science Advances, point towards new methods that may detect the earliest changes linked to Alzheimer’s.
Subjective cognitive decline has become an essential focus in dementia research. Although conventional memory and thinking tests do not show impairment, people with SCD often go on to develop Alzheimer’s dementia later in life. Professor Thomas Wolbers, who led the study in Magdeburg, explained that SCD may represent a preclinical stage of Alzheimer’s. Because the entorhinal cortex—the brain region housing our “internal compass”—is one of the first areas affected by the disease, researchers believe spatial orientation tasks may provide a more sensitive way of spotting early warning signs.
To test this theory, scientists designed a novel experiment in virtual reality. Participants aged between 55 and 89 walked in real space while wearing VR headsets that displayed a featureless digital plain. With no visual landmarks, they had to rely entirely on their brain’s navigation system, a process called “path integration.” In each trial, they followed a moving ball along a curved path, then were asked to point back to their starting position and align themselves with their original direction. Each person completed around 70 trials, producing a large dataset of orientation performance.
The results showed that, while ageing in general led to more errors, individuals with SCD performed consistently worse than those without it. Importantly, their difficulties could not be explained by walking speed or posture; instead, the errors were linked to cognitive processing. Mathematical modelling of the data revealed that people with SCD had particular problems keeping track of their previous positions in memory—a “memory leak” that disrupted their ability to stay oriented. Researchers suspect this is tied to dysfunction in the entorhinal cortex.
This brain region contains specialised “grid cells” that act like a coordinate system, storing a sequence of past positions and allowing us to keep track of where we are. If these cells are disrupted, as often happens in the early stages of Alzheimer’s, the ability to integrate paths becomes impaired. The DZNE team believe that testing for such subtle navigation errors could be a valuable new tool for early detection. Unlike conventional memory tests, orientation tasks may be sensitive to brain changes long before dementia symptoms appear.
Looking ahead, the researchers plan to refine their virtual reality test so it can be used in clinical trials and routine medical practice. For example, path integration could provide an additional measure when assessing the impact of experimental Alzheimer’s drugs, offering a more detailed picture of how treatments affect the brain. In the future, these methods may be combined with biomarkers from blood or spinal fluid to create highly accurate early diagnostic tools. Ultimately, the hope is that identifying Alzheimer’s at its earliest stage will open the door to more effective interventions and better outcomes for patients.
More information: Thomas Wolbers et al, Path integration impairments reveal early cognitive changes in subjective cognitive decline, Science Advances. DOI: 10.1126/sciadv.adw6404
Journal information: Science Advances Provided by DZNE – German Center for Neurodegenerative Diseases
