Helping Alzheimer's research through Online Gaming

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Author: Ines Barreiros Edited by: Emil Fristed

An early diagnosis is crucial to help slow down the progression of Alzheimer’s disease (AD). Unfortunately, with current diagnostic tools, AD is often diagnosed when patients are already experiencing significant cognitive impairment. We know that the disease affects people’s ability to find their way around – eventually sufferers get lost even in familiar environments. So, testing people on their navigation skills could potentially help diagnose AD. But we don’t yet understand well enough how people normally navigate. And, collecting sufficient data from a large enough sample of the population to study this can take a long time. What if everyone could help gather this data by simply playing a game on their phones?

Alzheimer’s disease

Alzheimer’s disease is the most common cause of dementia worldwide (60-70%). It develops over many years. Progressive neuronal damage results in memory loss and an increasing impairment in cognitive abilities – including language, navigation and problem-solving. At late stages, bodily functions such as walking and swallowing also deteriorate. As the disease progresses, AD sufferers lose their autonomy, becoming gradually incapable of attending to their own needs. Family and caretakers alike are emotionally distressed by the patient's deteriorating condition. Alzheimer’s disease is ultimately fatal (1).

Even though there are no effective treatments to stop the disease progression yet - let alone cure it - with early diagnosis, some drugs can help in slowing down and reducing the severity of its symptoms. Unfortunately, with the current diagnostic tools available, Alzheimer’s disease is often diagnosed much too late when patients are already experiencing substantial cognitive impairment. A diagnosis is considered late on average 6 months after the onset of marked memory loss. At this stage, symptoms become harder to slow down and treatments’ effectiveness more limited (2).

Biomarkers for AD

This has driven researchers to search for Alzheimer disease’s biomarkers – measures of biological processes which correlate with disease progression. Biomarkers can allow for an earlier diagnosis and, thus, maximize effectiveness of early medical interventions. They are not only useful in assessing the risk or presence of a disease. Their monitoring throughout time can also help keep track of the progress of the disease or how effective a medical treatment is.

Current validated biomarkers of AD include the levels of proteins involved in the pathophysiology of the disease in the cerebrospinal fluid (the liquid surrounding the brain). One of them is the pro-amyloid-β protein. When neurons’ cellular mechanisms fail to cleave and clear up the amyloid-β protein, its accumulation leads to neuronal damage and inflammation (3). The expression of genes strongly associated with Alzheimer’s disease in genome-wide association studies (GWAS) is another biomarker. Carrying certain genes has been revealed to represent a strong risk factor in the development of AD. One of those genes is APOE , which codes for a protein that transports lipids into neurons. The APOE ε4 variant of this gene has been associated with higher accumulation of the pathological amyloid-β protein aggregates (4).

These are not the only currently available biomarkers for the disease; there are others. But, so far, they all come with many caveats. Some AD’s screening tests involve difficult procedures that carry risks for the patient. Others are very expensive, limiting the frequency in which they are used to test patients. But perhaps the key problem is that the results obtained with current biomarkers are often not consistent with visible symptoms. There are patients which screen positive for the biomarkers but are free of cognitive symptoms. And there are patients with clear symptoms of the disease but no sign of abnormal protein levels (5).

Navigations skills – a potential AD biomarker?

In the face of the current AD’s diagnostic challenges, scientists are exploring different strategies in the search for alternative biomarkers of the disease. A characteristic symptom is the progressive decline of navigation abilities - getting lost even in a familiar setting has been proposed to be one of the first signs of Alzheimer’s disease. This happens because the hippocampus, a brain region involved in spatial navigation, is one of the first to be affected at the onset of AD (6).

Therefore, testing people on their navigation skills could potentially help diagnose Alzheimer’s disease. But not so fast. In order to understand how navigation gets worse with AD progression, we first need to understand how healthy people navigate and what they do when they get lost. This involves collecting data from healthy people – a lot of them!

Inviting people to physically come into the laboratory to collect this data costs researchers time and resources. Time, in such an urgent matter, is a key matter. In addition, it’s difficult to bring into the lab a large enough sample of the population to yield accurate results.

To tackle this problem, a team of scientists led by Dr Hugo Spiers  at University College London and by Professor Michael Hornberger at University of East Anglia, have turned to citizen neuroscience.

Sea Hero Quest online game – a crowdsourcing neuroscience project

Citizen science is scientific research with a substantial involvement from the public. Sometimes citizens' projects are led by amateur citizens trying to answer scientific questions on their own. Sharon Terry’s story is a famous example of an impressive amateur scientist-led project. She was a stay-at-home mom that decided to become a citizen scientist when her two children were diagnosed with a rare condition which no one seemed to know much about. More commonly, projects are designed and led by scientists with the public’s invaluable contribution in helping collect or analyse large sets of data. In Galaxy Zoo , a crowdsourced astronomy project, members of the public have helped to classify galaxies by analysing the data collected by scientists.

Citizen science projects have proved valuable  to help scientists analyse or gather vast amounts of data. The key to success of many of these projects, was to create a way through which people can help in a simple and engaging manner. As part of their endeavour to understand how people navigate, this team of neuroscientists developed Sea Hero Quest , an online game to crowdsource navigational skills data.