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

Summary

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.

Conditions

• Alzheimer Disease
• Aging

Interventions

DIAGNOSTIC_TEST

Cognitive assessment

Group 1: Cognitively healthy subject: After signing the consent form, during the only visit of the study, the investigator will administer to cognitively healthy subjects two cognitive screening tests to ensure that they meet the criteria for group 1. If performance on the cognitive scales prove to be borderline or below current standards (Montreal Cognitive Assessment ≥ 26/30 and MacNair Cognitive Difficulties Self-Rating Scale ≥15) for at least one of the 2 tests, the participant will prematurely end the study and may be offered an in-depth cognitive assessment as part of routine care. Group 2: Patients suffering from Alzheimer's disease: After signing the consent form, during the only visit of the study, the investigator will administer to patients the Montreal Cognitive Assessment to assess cognitive status.

OTHER

Questionnaires

For every participants (group 1 and 2): During the only visit of the study and after the intervention 1, the participants will answer questionnaires about: * Demographic data such as age, gender, weight, height, education level; * Lifestyle habits such as usual mode of transport, sense of direction, use of GPS device, and video game practice; * Quality of sleep over the previous month and the previous night; * Cognitive reserve questionnaire from Rami et al., 2011; * Concomitant treatment and comorbidities.

DEVICE

Spatial navigation task with eye-tracking.

For every participants (group 1 and 2): During the only visit of the study and after interventions 1 and 2, the participants will complete the spatial navigation task with eye-tracking. The participants will play the Sea Hero Quest video game and take on the role of the captain of a small boat that has to find its way through an aquatic environment. At the start of each level, the player is shown a map of the environment, with the boat's initial position and the buoys it must reach as quickly as possible in a set order. Once the map has been memorised, it disappears and the navigation begins. Participants will play 6 levels of Sea Hero Quest (two training levels and four different navigation levels). This intervention will be proposed by a trained team member and participants will play on a digital tablet connected to an eye-tracker. The total duration of the task is 30 min (training phase + assessment sequences).

BIOLOGICAL

Blood sampling

For every participants (group 1 and 2): During the only visit of the study and after interventions 1, 2 and 3, a state-qualified nurse will take venous samples from 3 tubes of 4ml each. These blood samples will be frozen and stored until the end of the study when they will be analysed: * Sample 1: plasmatic Quanterix p-tau217 assay; * Sample 2: apolipoprotein E genotyping; * Sample 3: measurement of plasmatic creatinine levels. Neither the cognitively healthy subjects, nor the patients, nor the clinicians in charge of the patients included will be informed of the results of these biological assays (absence of clinical interest established at the present time of the APOE genotype and the p-tau217 protein level, absence of modification of the care pathway, in adequacy to the bioethics law of August 02, 2021. Creatinine level is used in this study as an adjustment variable to interpret the p-tau217 protein level and will not be used for clinical interpretation.

Sponsors & Collaborators

• Hospices Civils de Lyon

  lead OTHER

Principal Investigators

• Antoine GARNIER-CRUSSARD · HCL

Study Design

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

20 Years

Max Age

85 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2024-03-01

Primary Completion

2025-09-01

Completion

2025-09-01

Countries

• France

Study Locations