Spatial and Ocular Trajectories for the Early Diagnosis of Alzheimer's Disease.

Spatial navigation is a high-level cognitive function that enables humans to orientate themselves and move around in space by constructing a mental representation of the environment. It is particularly interesting because it involves numerous neural networks, linked to proprioception and vision, for example.

Despite the versatility of this cognitive function, spatial navigation is little studied clinically, although changes in spatial planning and navigation strategies have been associated with many brain disorders, including Alzheimer's disease (Coughlan et al., 2018). This may be explained in view of the neuropsychological tests currently in use, which do not effectively assess spatial navigation disorders. In addition, many non-pathological parameters - in particular socio-demographic and lifestyle - (Wolbers \& Hegarty, 2010; Coutrot et al., 2018) affect spatial navigation performance. Separating the pathological component from these non-pathological factors in spatial navigation can be challenging.

In this context, Sea Hero Quest (SHQ) has been developed (Coutrot et al., 2018; Spiers et al., 2021) as an international-scale cognitive spatial navigation task that holds great promise for assessing spatial navigation performance during normal and pathological ageing. SHQ is a video game that implements classic tasks from the spatial cognition literature, and has enabled the trajectories of 4 million players with varied socio-demographic profiles to be collected.

In addition to the direct measurement of spatial displacements, eye movements, measured by eye-tracking, provide additional information on the cognitive processes associated with visual attention. The analysis of eye movements can provide valuable information about the strategies employed by humans during spatial navigation (Zhu et al., eLife 2023).

While it is well known that normal ageing and pathological ageing (e.g. in the context of Alzheimer's disease) affect performance in simple spatial navigation or visual attention tasks, the neurocognitive mechanisms involved in this deterioration remain poorly understood. The investigators hypothesise that the joint analysis of ocular and spatial traces will provide a more detailed understanding of the cognitive strategies deployed during a spatial navigation task, and therefore of these underlying mechanisms.

The investigators therefore propose to jointly study the association between two complementary cognitive functions: spatial navigation and visual attention, and their relationship with normal and pathological ageing (confirmed Alzheimer's disease, plasma biomarkers and genetic risk factors for Alzheimer's disease). The joint analysis of these different signals has never been carried out as part of research into normal ageing and Alzheimer's disease.


Eligibility Criteria:
Inclusion Criteria:

Cognitively healthy subjects:

* Participants aged between 20 and 85 years old;
* Participant affiliated or entitled to a social security scheme;
* Participants who have been informed and have given written consent.

Patients with Alzheimer's disease:

* Participant aged between 50 to 85 years old;
* Participant undergoing memory clinic consultations for a diagnosed Alzheimer's disease, at the stage of minor neurocognitive impairment or major neurocognitive impairment, according to the NIA-AA 2011 criteria (McKahn et al., 2011, Albert et al., 2011);
* Mild to moderate cognitive impairment, Mini-Mental State Examination (MMSE ≥ 20/30, in the 6 months prior to inclusion);
* Participant affiliated or entitled to a social security scheme;
* Participants who have been informed and have given written consent.

Exclusion Criteria:

For all participants:

* Severe, progressive or unstable pathology whose nature may interfere with the assessment variables (epilepsy, acute psychiatric or psychotic disorders, visual hallucinations, acute infection);
* Consumption of toxic substances that may affect cognitive performance;
* Deafness or blindness that could compromise the participant's assessment or participation in tasks and scales;
* Participants under guardianship or legal protection;
* Pregnant women, women in labour or breastfeeding mothers;
* Persons under psychiatric care.

Cognitively healthy subjects:

- Participants diagnosed with a cognitive disorder.

Specifically for patients with Alzheimer's disease:

* Participants with a diagnosis other than Alzheimer's disease that promotes neurocognitive impairment (with the exception of cerebral microvascular involvement, i.e. mild to moderate microangiopathy);
* Severe cerebral microangiopathy (extensive and severe white matter hypersignals, Fazekas score = 3);
* Severe psycho-behavioral manifestations preventing performance of the task, at the investigator's discretion;
* Current participation in an Alzheimer's disease drug research protocol, in particular testing 'disease-modifying' treatments that may interact with the pathophysiology of the disease (after randomisation).