The goal of this observational study is to evaluate the acceptability ofpatients with trisomy 21 (T21) to perform the full battery of ENDI neurospychological tests and each of the subsets.

In this study, three types of population will be recruted : normotypic volunteers, patients with Intellectual Disability and patients T21carriers.

This study is separated into 2 phases :

• A the preliminary phase : this phase will be used to evaluate subtest design, ergonomics and understanding of instructions, and to identify any malfunctions. The observations gathered will enable the principal investigator to refine the digital design of the battery in collaboration with the publishing company. In this phase, normotypical volunteers and patients with intellectual disabilities will be recruted to perform ENDI test battery.
• A main phase : this phase will enable to answer to the main objective. in this phase, patients with Trisomy 21 aged between 25 and 65 will be recruted to perform ENDI test battery.

Trisomy 21 is a genetic disease resulting from a chromosomal anomaly, due to a triplication, bringing the total number of chromosomes to 47. In addition to physical characteristics, adults with Trisomy 21 (T21) generally have an intelligence quotient (IQ) score suggesting mild (IQ: 50-69) to moderate (IQ: 35-49) intellectual disability (ID), and adaptive functional impairments corresponding to this level of ID severity. Progress in medical and social care has led to a significant increase in life expectancy for trisomy 21 patients. De Graaf, Buckley & Skotko (2021) estimate the number of trisomy 21 patients in France at around 35,000, 42% of whom are aged 40 or over. According to Asselin (2005), by 2030, the number of people with intellectual disabilities (ID) aged over 60 should have doubled.

This raises questions about the ageing of this population, all the more so as it is likely to occur earlier, due to reduced neuronal reserve. For example, signs of aging appear 10 years earlier in people with ID, at around age 55. Moreover, this aging process is said to be accelerated Normal cognitive aging in trisomy 21 patients is poorly characterized in the literature; similarly, there is no consensus regarding prodromal signs of Alzheimer's Disease (AD) in T21. However, the presence of the supernumerary chromosome containing the APP (Amyloid Precursor Protein) gene increases the risk of developing AD: 20% of trisomy 21 patients aged 45 and over develop a major neurocognitive disorder (MNCD), and over 50% by the age of 55. T21 is now considered a genetic form of AD, similar to an autosomal dominant form. Identifying AD in this population is therefore a real challenge, especially as AD is identified as the cause of 70% of deaths in trisomy 21 patients.

In cognitive terms, the precursor signs of AD are impairment of memory and temporo-spatial orientation, followed by impairment of praxis, language and visuo-spatial skills. Other authors suggest an early decline in executive functions. More recently, Startin et al. (2019) show that memory and attention tests are more sensitive in detecting prodromal forms. Establishing a diagnosis of neurodegenerative disease in trisomy 21 patients is important for at least 3 reasons. People with intellectual disabilities are often treated with neuroleptics, whose use is not recommended in AD. It also contributes to the adaptation of medical and social care, as ageing disabled people with AD will experience less frequent difficulties, including behavioural changes. According to the Edinburgh Principles, it is important to "ensure that appropriate diagnostic, assessment and intervention resources and services are available to meet the individual needs and promote the healthy ageing of people with intellectual disabilities and cognitive impairment". Finally, at a time when promising pharmacological treatments for AD are emerging for neurotypical subjects, it seems crucial that trisomy 21 patients, who are more at risk of AD, should be diagnosed as early as possible so that they can ultimately benefit from these new therapies. Neuropsychological assessment plays a crucial role in the diagnostic process, as brain imaging and lumbar puncture for AD biomarkers in cerebrospinal fluid are not always feasible.

However, a number of problems remain:

• Neuropsychological assessment is conditioned by the severity of the intellectual disability and the level of literacy/numeracy.
• Few adapted tests are available in French. Tests used in the general population are not transposable, and those based on child assessment batteries are infantilizing.
• Few tests incorporate the evolution of digital technologies, which make it possible to offer more playful interfaces with better temporal control.
• Few tests allow for longitudinal follow-up (no parallel versions, no longitudinal standards), whereas current recommendations call for systematic annual follow-up from the age of 30. In this context, it is essential to develop new cognitive tools integrating digital technologies and innovative approaches, which are indispensable for accurate diagnosis and monitoring of cognitive disorders in trisomy 21 patients. It was with this in mind that the ENDI (Evaluation Neuropsychologique dans la Déficience Intellectuelle) battery was designed. This neuropsychological battery comprises 15 subtests designed to assess language, memory, attention and executive skills. By analyzing changes in trisomy 21 patients performance over time, the neuropsychologist can detect early signs of AD. A pre-test of the ENDI battery is planned to evaluate subtest design, ergonomics and comprehension of instructions, and to identify any malfunctions. The observations gathered will enable the principal investigator to refine the digital design of the battery in collaboration with the publishing company.

Inclusion Criteria:

Preliminary phase:

1. The inclusion criteria for the group of people with intellectual disabilities are as follows:

   • Participant who has received full information on the organization of the research and has not objected to his or her participation and to the use of his or her data.
   • Legal guardian of the participant, if applicable, who has received full information on the organization of the research and has not objected to participation and use of his/her data.
   • Age at inclusion: ≥ 25 and ≤ 65 years
   • Notion of intellectual disability in medical records
   • Access to the oral language of the participant with an intellectual disability: the subject's speech must be comprehensible to the evaluator and the subject must be able to understand simple statements. It is not possible to use an oral comprehension test (e.g. Token test by Renzi & Vignolo, 1962), as the norms achieved in healthy subjects would exclude almost all patients with intellectual disabilities, who have more limited language skills.
   • Enrolled in or benefiting from a social security scheme.

2. The inclusion criteria for the normotypic group are as follows:

   • Participant having received full information on the organization of the research and not having objected to his or her participation and to the use of his or her data.
   • Age at inclusion: ≥ 25 and ≤ 65 years
   • Affiliation with a social security scheme or beneficiary of such a scheme

Main phase:

Inclusion criteria are as follows:

• Participant with T21 who has received full information on the organization of the research and has not objected to participation and use of his/her data
• Legal guardian of the participant with T21, where applicable, who has received full information on the organization of the research and has not objected to his or her participation and the use of his or her data.
• Person with trisomy 21
• Age at inclusion: ≥ 25 and ≤ 65 years
• Access to the oral language of the participant with T21: the subject's speech must be comprehensible to the evaluator and the subject must be able to understand simple statements. It is not possible to use an oral comprehension test (e.g. Token test by Renzi & Vignolo, 1962), as the norms achieved in healthy subjects would exclude almost all patients with intellectual disabilities, who have more limited language skills.
• Membership of a social security scheme or beneficiary of such a scheme

Exclusion Criteria for both phases of the study are as follows:

• Disabling motor and/or sensory impairments preventing completion of the tests

• Insufficient command of the French language to complete the tests

• Severe general medical condition or alcoholism (habitual consumption of 3 drinks/day or history of alcohol withdrawal)

• History of stroke, severe head trauma, or cancer

• Change in long-term medication within 8 weeks prior to evaluation

• Refusal to participate by the subject and/or legal representative

• Individuals referred to in Articles L.1121-5 to L.1121-7 of the French Public Health Code:

  • Pregnant women, women in labor, or breastfeeding mothers
  • Individuals deprived of liberty by judicial or administrative decision
  • Individuals undergoing psychiatric treatment under Article L.3213-1 of the French Public Health Code

Normotypical volunteers, patients with intellectual disability, and Trisomie 21 patients (T21) will be recruited by psychologists during a consultation in the Geriatrics Department of the University Hospital of Nancy, either through the Memory Resource and Research Center outpatient clinic or the day hospital. Volunteers and patients are generally referred by their general practitioner or another hospital department.