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Navigational Errors Offer Clue to Early Alzheimer's Disease

A small trial using virtual reality to assess subtle variations in how people walk and navigate their way through virtual space suggested that certain navigational mistakes may represent early signs of Alzheimer's disease. 

The study, hailed as "promising" by experts, could offer the hope of earlier diagnosis of the condition, estimated to affect over 566,000 people in the UK.

Researchers from the Institute of Cognitive Neuroscience at University College London (UCL) built on their previous research, carried out in collaboration with the University of Cambridge, showing that virtual reality could be used to spot changes in how people with early Alzheimer's disease (AD) navigate. They explained that people's ability to update their estimated location and orientation using self-motion signals, including optic flow and vestibular and proprioceptive feedback, is a crucial ability for locomotion. 

Impaired Location and Orientation Assessments in MCI

This skill, called path integration (PI), is known to be disturbed early in the development of AD. "Impaired PI is a sensitive and specific behavioral marker of pre-dementia of AD, manifesting in mild cognitive impairment (MCI)," the authors explained. However this reflects multiple sub-processes that may be differentially sensitive to AD. They reasoned that being able to assess these might enable more precise cognitive tests for dementia at earlier stages, as well as with higher diagnostic sensitivity than currently available tests.

For their new study, published in Current Biology, they developed a computational model to assess which PI components were disrupted when participants undertook a triangle completion perambulation task while wearing immersive virtual reality goggles, which allowed them to make real movements. Participants were 31 healthy younger people (mean age 21.2), 36 healthy older people (mean age 68.3), and 43 patients with MCI (mean age 71.4). Among the latter, 11 had biomarkers for AD in their cerebrospinal fluid (CSF), 14 had negative CSF, and 18 unknown biomarker status. 

In the virtual reality world, participants had to walk an outbound route guided by numbered cones, consisting of two straight legs connected by a turn. They then had to return to their starting position unguided. The task was performed under three different environmental conditions aimed at increasingly stressing navigational skills: an unchanged virtual environment, one with the ground details replaced by a plain texture, and one in which all landmarks had been temporarily removed.

People With MCI Consistently Overestimated Angular Turns 

Results showed that the participants with MCI consistently overestimated the angular turns on the outbound path and showed increased variability in their inbound distances and sense of direction, compared with healthy adults. Those with MCI plus AD biomarkers could be distinguished from those without biomarkers by overestimation of outbound turns and more variable inbound directions.

The researchers said that these navigational errors therefore seemed specific to AD, rather than an extension of healthy ageing or general cognitive decline. They suggested the findings could offer a new avenue for early AD diagnosis, so improving management and treatment, while acknowledging that more confirmatory work was needed.

Joint first author Dr Andrea Castegnaro, a research fellow at UCL, said: "We aim to develop practical tests that can be easily integrated into clinical settings, considering common constraints such as limited space and time." While cognitive assessments would still be needed, these tests could offer a practical advantage over existing spatial memory tests that often rely on verbal competence affected by language and cultural background.

Study Offers Valuable Insight

Asked to comment on the study by Medscape News UK, Siân Gregory, research communications manager at the Alzheimer's Society, said that diagnosing dementia could be problematic, with very early symptoms often subtle and hard to detect. "Problems with navigation are thought to be some of the earliest noticeable changes in AD", she said, so the findings offered "valuable insight".

She pointed out that the technology was in its infancy, and work was needed to improve its accuracy. However, "it may offer a way to detect disease-specific brain changes in the early stages of dementia, potentially benefiting hundreds of thousands living with the condition in the future".

Also commenting to Medscape News UK, Dr Leah Mursaleen, head of research at Alzheimer's Research UK, said that thanks to "limitations in current methods of detection", only around 60% of the almost 1 million people with AD in the UK would ever receive a diagnosis. "It's vital that we develop new, more precise early detection techniques that can be easily used in healthcare systems like the NHS," she said. "This will be particularly important as we enter an era where dementia becomes a treatable condition."

A larger study was needed to understand the future potential of "this promising discovery", she said. "It will also be important to understand how digital technologies like this can be used in combination with other emerging techniques like blood tests, which are also showing huge promise for detecting AD."

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