Impaired spatial orientation found in older adults at risk for Alzheimer’s disease

Individuals with an increased risk for dementia due to Alzheimer’s disease can have impaired spatial orientation skills. DZNE researchers come to this conclusion based on a study involving around 100 older adults who were tasked with determining their position within a virtual environment. In this, participants with “subjective cognitive decline” (SCD) – a risk factor for Alzheimer’s disease – performed worse than members of the control group. In contrast, there were no significant differences in conventional tests of cognitive performance. In view of this, the current research results, published in the journal Science Advances, could pave the way for more sensitive testing methods. Potential areas of application include early diagnosis of Alzheimer’s and drug studies.

The term “subjective cognitive decline” (SCD) refers to the condition in which someone believes that their memory is deteriorating, despite standard tests showing no decline in mental performance.

This condition has been the focus of research in recent years, because people with SCD are known to be at an increased risk of developing Alzheimer’s dementia later in life. It is therefore reasonable to assume that SCD may indicate a preclinical stage of Alzheimer’s.”

Prof. Thomas Wolbers, research group leader at DZNE’s Magdeburg site and member of the Collaborative Research Centre “Neural Resources of Cognition”

Novel approach

In the current study, the team led by the Magdeburg-based neuroscientist explored an approach for detecting cognitive impairments that goes beyond conventional test methods. Experts from the US and the Czech Republic collaborated on this research. Together, they assessed what is known as path integration: This refers to the ability to determine position and navigate spatially based on body awareness and the perception of one’s movement. “For this task, we humans use special neuronal circuits. They are located in an area of the brain called the entorhinal cortex. Hence, in a sense, we carry a compass inside our heads,” says Wolbers. Alzheimer’s disease typically affects this area in its earliest stages, even before symptoms of dementia manifest. “This brings us full circle to our current study. To my knowledge, our findings are the first to show that SCD can be associated with subtle orientation problems. We hope this will lay the foundation for novel testing methods that can detect very early effects of Alzheimer’s disease,” says Wolbers.

A world without reference points

The study included 102 older women and men, aged between 55 and 89. Thirty of the participants had SCD. However, all study subjects scored within the normal range on conventional cognitive tests. For the actual experiment, they wore a virtual reality headset. Equipped with these, they walked through real space while simultaneously moving through a computer-generated environment: They saw an endlessly vast plain with no landmarks under a blue sky. However, the irregular texture of the ground enabled them to perceive their movements across the digital landscape. “Since there were no visual landmarks in this virtual world, the only way to orient oneself was with the help of the brain’s navigation system. This is precisely the ability we wanted to test,” says Dr. Vladislava Segen, first author of the current publication and a member of Wolbers’ research group.

Putting the brain’s compass to the test

The task began with the study participants following a ball that floated near the ground while moving along a curved trajectory until it finally came to a stop. Once the participants had caught up with the ball, they were asked to turn toward their original starting point and mark its presumed position. To do this, they used a virtual pointer that could be operated via a hand controller. The participants were also asked to align themselves with the direction they had been facing at the initial start of their path. “This allowed us to test how well the study subjects could remember their initial orientation,” says Segen. The ball then hovered on to the next stop, where the responses had to be repeated. With two stops per run, the total distance covered in real space was approximately six meters, and each participant completed about 70 trials. This allowed to collect extensive data on the movements of the study subjects and how accurately they performed their orientation tasks.

Less accurate with SCD

“Some found these tasks easier than others. They were certainly challenging. In general, there was a clear age-related effect with the oldest individuals showing larger errors. This applied regardless of whether SCD was existent or not,” says Segen. “However, when comparing the groups, it became obvious that participants with SCD performed worse overall. They were less accurate in path integration. Our data suggest that these orientation difficulties did not arise from movement dynamics, such as walking faster or looking at the ground more often while walking. The causes of the imprecise orientation were not related to motion, but cognitive in nature.”

Deeper insights with mathematical modeling

To identify the causes of this impairment in more detail, the research team applied complex mathematical modelling to the collected data. “The brain has to process various data to determine position. This includes correctly perceiving the speed at which you are moving and the direction in which you are going. With the help of our model, we were able to identify which sources of error had the greatest impact on position determination and which had only minor influence,” says Segen. One factor stood out, with its influence on position accuracy differing significantly between the two study groups. “To determine your position in space while moving, you have to constantly update your position in your mind. This requires you to remember previous positions. To do this, you unconsciously draw on a mental history. In people with SCD, this type of memory was particularly faulty. We therefore refer to this as memory leak. We suspect that functional disturbances in the entorhinal cortex are responsible for this”, explains Segen.

Clinical implications and future directions

The entorhinal cortex contains a special type of neurons called “grid cells”. Based on incoming sensory information, those cells generate a kind of coordinate system for the environment in which a person currently finds themselves. Studies by other research groups suggest that these neural circuits store a history of previous, successive locations in memory – similar to the sequence of images in a flipbook. “The evidence is converging that path integration is very sensitive to grid cell dysfunction and thus to preclinical stages of Alzheimer’s disease,” says Thomas Wolbers. Thus, the researchers want to further develop their experimental setup so that it can be used in clinical trials. “I am thinking, for example, about testing new drugs. When evaluating the effects of novel active substances, path integration could supplement existing assessments to provide a more detailed overall picture,” says Wolbers. “In the long term, I also see potential for use in clinical routine, specifically in the early diagnosis of Alzheimer’s disease. However, this technique first needs to be further tested and simplified. Also, we intend to relate our findings to biomarkers for Alzheimer’s disease derived from blood or cerebrospinal fluid. This should provide further insights into the capability of our approach for detecting neurodegeneration.”

This article was originally published on news-medical