ICOD for you


Deficits of executive functions (working memory and memory flexibility) have a strong impact on Down syndrome (DS) individuals and largely reduce the ability of children with DS to learn even mildly complex tasks.1,2

The ICOD project focuses, for the first time, on working memory and memory flexibility deficits in DS.

There are different cognitive screening tests and tools developed that are currently used in clinics to detect cognitive impairment and assess the effect of drugs,3 but no official guidelines have been developed to assess cognitive deficits in Down syndrome subjects or their impact on quality of life of Down syndrome individuals and their families.

Developing a treatment for cognitive impairment and in particular for working memory deficits is extremely challenging. A first big issue is the lack of international consensus on validated and accepted cognitive psychometric tools able to detect the potential clinical efficacy of a new drug. Another major problem in the development of therapies for cognitive impairment is that studies in animals and in humans often study different behavioral and cognitive phenotypes.

The NIH Toolbox represents an innovative psychometric approach to investigate improvement of working memory.

Which tools are we going to use?

In the ICOD project, we will primarily use the NIH Toolbox Cognitive Battery in intellectual disability (NIHTB-CB for ID), composed of seven neuropsychological tests analyzing different cognitive abilities.

The fluid cognition composite score has been specifically developed4 to evaluate cognitive impairment in intellectual disabilities and is the primary efficacy endpoint in the ICOD project. It combines the scores of five tests assessing:

  • Attention
  • Episodic memory
  • Working memory
  • Cognitive flexibility
  • Processing speed

The NIH toolbox represent an innovative psychometric approach that should be able to demonstrate the clinical efficacy of AEF0217 in improving working memory, learning skills and in autonomy and quality of life.

1. Lanfranchi S, Jerman O, Dal Pont E, Alberti A, Vianello R (2010). Executive function in adolescents with Down syndrome. J Intel Disabil Res 54:308–319.
2. Esbensen AJ, Hooper SR, Fidler D, Hartley SL, Edgin J, d’Ardhuy XL, Capone G, Conners FA, Mervis CB, Abbeduto L, Rafii MS, Krinsky-McHale SJ, Urv T; Outcome Measures Working Group. Outcome Measures for Clinical Trials in Down Syndrome.Am J Intellect Dev Disabil. 2017 May;122(3):247-281. doi: 10.1352/1944-7558-122.3.247.
3. Hessl D, et al. The NIH Toolbox Cognitive Battery for intellectual disabilities: three preliminary studies and future directions. J Neurodev Disord. 2016 ;8(1):35;
4. Shields RH, et al. Validation of the NIH Toolbox Cognitive Battery in intellectual disability. Neurology. 2020 Feb 24. pii: 10.1212/WNL.0000000000009131.