Castegnaro, Andrea; (2021) Testing Spatial Cognition in Mild Cognitive Impairment Using Immersive Virtual Reality. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The prodromal stage of dementia is known as mild cognitive impairment (MCI). Currently, cognitive tests are unable to correctly characterize the MCI type, and specifically, whether it will develop into Alzheimer's disease (AD). This means that cognitive deficits are detected long after the onset of pathological changes. More sensitive and specific tests, which can non-invasively detect the subtle, early signs of AD in MCI, would facilitate investigation of its early development and potentially permit early treatments. This thesis aims to develop a diagnostic tool to target the cognitive functions – and engage the corresponding brain regions – typically affected during the prodromal stages of AD. Pathological changes start in the hippocampal formation, a critical area for episodic memory and navigation. The tasks are developed from previous work demonstrating hippocampal dependence and make use of recent advances in immersive virtual reality, providing an ecologically valid improvement on standard tests of cognitive function. The first experimental chapter presents a test of navigation by path integration, a function specifically associated with processing by grid cells in the medial entorhinal cortex (mEC). The second experiment presents a test of object-location memory, believed to involve place cells in the hippocampus proper, combining inputs from mEC and object-identity information from the lateral entorhinal cortex (lEC). The third experiment tests object-location memory in a way that enables the contribution of self-motion to be assessed. Results show that the immersive virtual reality paradigms developed to test spatial cognition in prodromal AD are able to differentiate MCI patients from healthy age-matched older controls. Additionally, in combination with CSF biomarkers, navigation testing has proven the ability to stratify between MCI with different levels of biomarkers, identifying the patients who are most likely going to develop the disease. Finally, the last experiment, in an attempt to summarize different aspects of spatial cognition tested in the previous experiments, can detect subtle changes starting from ageing that may further decline with the onset of cognitive decline due to AD neuropathology. In conclusion within this thesis, we demonstrated the use of immersive virtual reality tests as an ecological valid tool for assessing the behavioural changes associated with the early progression of AD.

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