"Alzheimer's disease changes lives. Even though the disease is gradual no one is ever ready for the impact it has on family relationships and responsibilities," says Dr Paula Bolger, whose company, Cortex Cognition, is developing digital biomarkers to objectively monitor the progress of Alzheimer's and detect the subtle changes that can indicate its early stages.
“We know that the changes brought about by the disease occur in the brain years, if not decades, before the symptoms emerge,” Bolger says. “New therapies are increasingly focused on treating people before they develop symptoms with a view to preventing the development of dementia and hitting the disease when it may be more responsive. At the moment the lack of screening for high-risk populations in particular means that Alzheimer’s detection is occurring late and often 10-15 years from onset.”
Cortex Cognition’s patent-pending technology aims is to do two things: simplify the way in which levels of cognition are measured and accelerate the commercial availability of tests that can do this.
To cut to the chase it has “borrowed” from the gaming industry and is applying the same sort of immersive virtual reality found there to brain function testing. The tests are structured to assess an individual’s performance through a series of cognitive challenges and the results provide a picture of their current level of brain function. This can then be used as a baseline for future testing.
“The tests still widely used in hospitals today are pen and paper based, and they require the input of a neuropsychologist and there aren’t very many of them available in any country. As a result these tests are not scalable or really fit for purpose any more. There is a big need for new ways of testing and monitoring people,” Bolger says.
“Different [neurological] diseases also have different pen and paper tasks, and all the scores mean different things so we’re trying to simplify the process by creating tasks that will apply across diseases. There’s also an issue around monitoring or lack of it over time. As of now people are put on medication but there is no regular monitoring of how it is affecting their condition. This would be feasible with our testing method which is a lot more scalable than using MRIs for example.
Pre-clinical disease
"Our aim is to be the first virtual reality computerised cognitive assessment aid with regulatory approval for commercialisation in Europe and the United States, " adds Bolger, whose company currently employs five people.
“Our technology is designed to be used for a wide range of neurological conditions including multiple sclerosis and Parkinson’s but we are initially focusing on Alzheimer’s disease because the most commonly used clinical test, the mini mental state exam, does not detect pre-clinical disease. Only 10 per cent of patients with Alzheimer’s disease are currently diagnosed at the pre-clinical stage.”
Bolger says a combination of advances in virtual reality devices and discreet motion sensors as well as increases in computer power and data analysis offer real possibilities when it comes to making diagnoses more specific.
“We can combine these tools with deep analytics and ipsative scales [a type of measure used in personality and attitude assessments] to target, personalise and create a very powerful precision medicine solution. This is a game-changer for dementia risk.”
Before setting up Cortex Cognition in 2016, Bolger worked in the digital health sector, and led the development of new products for both healthcare providers and pharmaceutical companies. One aspect of her role was looking for real world evidence that drugs were working, and the main way of collecting this information was by simply asking people.
“Patients would be asked ‘how is your memory?’ They would give a response and that would be used to score whether the drugs were working or not,” Bolger says. “But people that are getting older don’t always tell the truth so it’s not a performance-based measure of how their memory really is. It’s a subjective interpretation. I believed there needed to be proper performance-based measurement, and that’s where the idea for Cortex Cognition came from.”
Initially Bolger started the process of developing Cortex Cognition with a small team, and spent a year working on the idea before deciding that the project would benefit from an academic collaboration on its neuroscience aspects. To achieve this she spun her company into Trinity College at the end of 2017, and all going well it will be spun out early next year.
Neuroscience
“I had a good relationship with Trinity because I came from there myself, so I decided to spin in to the university with the aim of being there for two years working with the institute of neuroscience,” Bolger says.
“Before we went into Trinity we had already built prototypes and done a lot of work around the technology as I wanted to see if was technically feasible to do everything I wanted to do. Virtual reality (VR) is at a great stage but there are still some technical challenges, and I wanted to see would it actually work for us. So we had already done all of that development, and the focus in Trinity has been on the neuroscience.”
Bolger knew that trying to measure performance using old fashioned methods was not going to cut the mustard. Her interest was in how people really responded when tested and not in how they thought or said they did. This led her towards gaming because so much of gaming is about behaviour and the play environments are so realistic.
“I was a nurse in a previous life, so I’m aware of the challenges of working in the health system and that’s always been at the back of my mind. It’s one thing bringing technology to the health sector, but it’s no good if it’s too difficult for people to use, and VR is much easier and more effective for our purposes than an iPad for example.”
There are six core areas of cognitive function, and the company has built a series of clinical tests around each of them. In Alzheimer’s disease spatial cognition is the first domain to be hit and Bolger says “VR is absolutely perfect for spatial tests. You can’t really do them well on an iPad or with a pen and paper. We currently have no competitor with a suite of virtual reality-based tests that cover all the domains of cognitive function.”
The Cortex Cognition system considers both performance and behaviour, and is based around a VR headset which the patient wears. It “understands” gestures so there are no controls that might distract the person and have an impact on their reactions. Everything the person does during a typical 15-minute test is monitored and this provides the clinicians with 1.25m data points which are analysed to identify impairment traits. For example, people with Parkinson’s may unconsciously roll their eyes and this behaviour is picked up by the headset camera.
Healthcare providers
Cortex Cognition is a B2B product aimed at healthcare providers, insurers, employers offering wellness programmes and pharmaceutical companies. Bolger self-funded the initial phase of the start-up before a €400,000 commercialisation grant kicked in from Enterprise Ireland.
The company’s revenue model will be a combination of licensing and pay per test, and it is now looking to raise around €1.5 million to complete development and prepare the product for regulatory approval.
“This is a software medical device so it’s not actually the VR that’s the expensive part. It’s the whole back-end platform that has to be built, including the piece around data protection in multiple countries,” Bolger says.
The market potential for the company’s Alzheimer’s test is very large as in the US alone the aim is to screen everyone over the age of 55 on an annual basis. In Europe the focus is more on high-risk groups which is a cohort of over 80 million people in the region’s five largest countries.
"I'm really keen to have local involvement in the validation process at this early stage, and to be able to do my studies in Ireland rather than having to go to the NHS, " Bolger says. "Right now we're engaging with two Dublin hospitals around Alzheimer's disease and multiple sclerosis, but another area we are interested in is oncology because when you take chemotherapy it damages your brain."
The company hopes to be market-ready in 2021, and Bolger says that when all of the clinical and B2B testing is complete it will be looking at releasing “light” versions of its products so people can do training and complete assessments on their phones at home.
Bolger’s original team is still with her, and she says that had they been motivated by money they would be long gone.
“They could have been earning plenty if they were in financial services or some other lucrative sector, but they are part of a growing group who are very passionate about working in an area where their skills can genuinely make a difference.”
