New video game developed to help identify attention deficit disorder in children

A team of researchers has developed a platform that allows the identification and evaluation of the degree of attention deficit hyperactivity disorder (ADHD) in children and adolescents. The study was led by researchers from the Universidad Carlos III de Madrid (UC3M) and the Complutense University of Madrid (UCM, in its Spanish acronym), among other institutions.

ADHD is a neurodevelopmental disorder with an estimated prevalence of 7.2 per cent in children and adolescents, according to the latest evaluations.

It is clinically diagnosed on the basis of the judgement of healthcare professionals using the patient’s medical history, often supported by scales completed by caregivers and/or teachers. No diagnostic test has been developed for ADHD to date.

In a paper recently published in Brain Sciences, this team of researchers proposed using a video game that children are already familiar with to identify the symptoms of ADHD and evaluate the severity of the lack of attention in each case.

In this game genre, the player has a running avatar, which they have to use to avoid different obstacles on their way. “In our game, the avatar is a raccoon that has to jump in order to avoid falling into holes it encounters on its route,” explains David Delgado Gomez, the lead author and professor at the UC3M’s Department of Statistics.

“We hypothesise that children diagnosed with ADHD inattentive subtype will make more mistakes by omission and will jump closer to the hole as a result of the symptoms of inattention,” says another author Inmaculada Penuelas Calvo, a psychiatrist at Jimenez Diaz Foundation University Hospital and professor at the UCM’s Department of Personality, Evaluation and Clinical Psychology.

The main benefit of this study is that it allows symptoms of attention deficiency to be directly identified so that the severity of the patient’s inattention can be objectively assessed, say the researchers. Therefore, it could be used to supplement the initial diagnosis as well as to assess the evolution of symptoms or even the effectiveness of treatment.

There are also other important advantages such as the fact that each test would only take seven minutes to complete and does not require specific hardware, which reduces its cost significantly. In fact, conventional personal computers, tablets, or mobile devices can be used, allowing remote assessments to be done.

“Our results indicate that a shorter test may be enough to accurately assess the clinical symptoms of ADHD. This feature makes it particularly attractive in clinical settings where there is a lack of time,” the researchers note.

A rapid test that allows early diagnosis

The study was carried out in collaboration with a group of 32 children, between 8 and 16 years of age, diagnosed with ADHD by the Child and Adolescent Psychiatry Unit at the Jimenez Diaz Foundation University Hospital.

As each child was taking the test, supervised by a trained professional, the appropriate caregiver completed the inattention subscale in the attention deficit hyperactivity disorder and normal behaviour symptom classification scale (SWAN), which is an inventory of reports from parents and caregivers developed to evaluate the ADHD symptoms. In the game, the raccoon has to jump over 180 holes that are grouped into 18 blocks.

“Each block is identified by the speed of the raccoon, the length of the trunk, and the width of the hole. The length of the trunk and the speed of the avatar determine the time between stimuli, which is about 1.5, 2.5, and 3.5 seconds, while the width of the hole determines how difficult it is to jump over,” Penuelas explains.

Currently, ADHD diagnosis depends mainly on the healthcare professionals’ experience and the teacher or caregiver’s observation skills. Several studies have determined that these assessments may be altered, by affective factors for example.

Therefore, “the development of diagnostic methods such as those proposed in this paper may favour early diagnosis and thus improve these patients’ prognosis,” Gomez concludes.

 

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New design strategy marks a potential advance in the fight against Alzheimer's disease

Researchers have found a way to design an antibody that can identify the toxic particles that destroy healthy brain cells - a potential advance in the fight against Alzheimer's disease.

Their method is able to recognize these toxic particles, known as amyloid-beta oligomers, which are the hallmark of the disease, leading to hope that new diagnostic methods can be developed for Alzheimer's disease and other forms of dementia.

The team, from the University of Cambridge, University College London and Lund University, designed an antibody which is highly accurate at detecting toxic oligomers and quantifying their numbers. Their results are reported in the Proceedings of the National Academy of Sciences (PNAS).

There is an urgent unmet need for quantitative methods to recognise oligomers - which play a major role in Alzheimer's disease, but are too elusive for standard antibody discovery strategies. Through our innovative design strategy, we have now discovered antibodies to recognise these toxic particles."

Michele Vendruscolo, Study Lead Author and  Professor, Cambridge Centre for Misfolding Diseases

Dementia is one of the leading causes of death in the UK and costs more than £26 billion each year, a figure which is expected to more than double in the next 25 years. Estimates put the current cost to the global economy at nearly £1 trillion per year.

Alzheimer's disease, the most prevalent form of dementia, leads to the death of nerve cells and tissue loss throughout the brain, resulting in memory failure, personality changes and problems carrying out daily activities.

Abnormal clumps of proteins called oligomers have been identified by scientists as the most likely cause of dementia. Although proteins are normally responsible for important cell processes, according to the amyloid hypothesis, when people have Alzheimer's disease these proteins -including specifically amyloid-beta proteins - become rogue and kill healthy nerve cells.

Proteins need to be closely regulated to function properly. When this quality control process fails, the proteins misfold, starting a chain reaction that leads to the death of brain cells. Misfolded proteins form abnormal clusters called plaques which build up between brain cells, stopping them from signalling properly.

Dying brain cells also contain tangles, twisted strands of proteins that destroy a vital cell transport system, meaning nutrients and other essential supplies can no longer move through the cells.

There have been over 400 clinical trials for Alzheimer's disease, but no drug that can modify the course of the disease has been approved. In the UK, dementia is the only condition in the top 10 causes of death without a treatment to prevent, stop, or slow its progression.

"While the amyloid hypothesis is a prevalent view, it has not been fully validated in part because amyloid-beta oligomers are so difficult to detect, so there are differing opinions on what causes Alzheimer's disease," said Vendruscolo.

"The discovery of an antibody to accurately target oligomers is, therefore, an important step to monitor the progression of the disease, identify its cause, and eventually keep it under control."
The lack of methods to detect oligomers has been a major obstacle in the progress of Alzheimer's research. This has hampered the development of effective diagnostic and therapeutic interventions and led to uncertainty about the amyloid hypothesis.

"Oligomers are difficult to detect, isolate, and study," said Dr Francesco Aprile, the study's first author.

"Our method allows the generation of antibody molecules able to target oligomers despite their heterogeneity, and we hope it could be a significant step towards new diagnostic approaches."
The method is based on an approach for antibody discovery developed over the last ten years at the Centre for Misfolding Diseases.

Based on the computational assembly of antibody-antigen assemblies, the method enables the design of antibodies for antigens that are highly challenging, such as those that live only for a very short time.

By using a rational design strategy that enables to target specific regions, or epitopes, of the oligomers, and a wide range of in vitro and in vivo experiments, the researchers have designed an antibody with at least three orders of magnitude greater affinity for the oligomers over other forms of amyloid-beta.

This difference is the key feature that enables the antibody to specifically quantify oligomers in both in vitro and in vivo samples.

The team hopes that this tool will enable the discovery of better drug candidates and the design of better clinical trials for people affected by the debilitating disease.

They also co-founded Wren Therapeutics, a spin-out biotechnology company based at the Chemistry of Health Incubator, in the recently opened Chemistry of Health building, whose mission it is to take the ideas developed at the University of Cambridge and translate them into finding new drugs to treat Alzheimer's disease and other protein misfolding disorders.

The antibody has been patented by Cambridge Enterprise, the University's commercialization arm.

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