Virtual reality headsets can reveal navigational issues in people at increased risk of Alzheimer’s disease before any declines in memory appear, research shows.
The headsets flagged spatial navigation problems even when there were no concerns in cognitive tests, according to the findings in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
Spatial issues specifically related to path integration, a form of navigation in which a person uses self-motion cues to estimate their position in the environment.
The findings are consistent with the idea that Alzheimer’s-related tau proteins initially deposit in the entorhinal cortex of the brain—whose grid cells are crucial to path integration—where they disrupt the spatially-related firing of neurons.
The research may improve the detection of the clinical onset of Alzheimer’s, which is critical for the prompt use of treatment.
“Our results indicated that this type of navigation behaviour change might represent the very earliest diagnostic signal in the Alzheimer’s disease continuum—when people move from being unimpaired to showing manifestation of the disease,” said Coco Newton, a cognitive neuroscientist now at the University of Cambridge, who carried out the work while at UCL.
The team tested the spatial navigation of 100 cognitively healthy, middle-aged adults, aged 43 and 66 years who had a hereditary or physiological risk of Alzheimer’s disease.
This was due to either carrying the APOE-ε4 allele or having a family history of Alzheimer’s disease, each of which is associated with a three-fold increase in risk, or alternatively having lifestyle risk factors such as low levels of physical activity, education levels or vascular health indicators.
The participants, who were recruited from the PREVENT-Dementia prospective cohort study, were approximately two decades younger than their estimated age for the onset of dementia.
Their ability on path integration in immersive virtual reality was compared with other cognitive domains, with behavioral data in some also compared with brain structure and function on 7T magnetic resonance imaging (MRI).
The team found that impaired path integration predicted both a hereditary and physiological risk of Alzheimer’s disease.
Crucially, this occurred without similar impairment in other aspects of spatial behavior or in episodic memory tests. The path-integration issues were associated with altered functional MRI signal in the posterior-medial entorhinal cortex.
There appeared to be a sex effect, with hereditary at-risk males particularly impaired on path integration and a tentative univariate observation that women who had a parental family history of Alzheimer’s disease were impaired on an egocentric virtual shopping trolley task.
The researchers say this may reflect sex differences in navigational strategy, with women tending towards landmark or route navigation, and men towards survey-based allocentric mapping. However, they add that it could also reflect sex differences in the pathological spatiotemporal progression of Alzheimer’s disease, with greater early parietal tau pathology in females.
They conclude that impaired path integration could be an initial behavioral change in Alzheimer’s disease prior to memory decline, and as such may represent the critical point transition from at-risk status to clinical disease onset.
“We are now taking these findings forward to develop a diagnostic clinical decision support tool for the NHS in the coming years, which is a completely new way of approaching diagnostics and will hopefully help people to get a more timely and accurate diagnosis,” said Newton.
“This is particularly important with the emergence of anti-amyloid treatments for Alzheimer’s, which are considered to be most effective in the earliest stages of the disease.”
