Dementia & Alzheimer’s disease
The Centre’s leadership in Alzheimer’s and dementia research is geared toward a singular focus: to create real results for patients and their families through excellent science; and different and courageous research approaches.
The need is great; the opportunity to help millions is an enormous responsibility.
Postponing onset of Alzheimer’s and dementia by 5 years would result in over 300,000 less people in Australia getting the disease. This represents a decrease of 30%.
If we could delay onset by 2 years, it would result in a 13% reduction of dementia by 2050.
Solving the mystery of Alzheimer’s disease is critical to bolstering Australia’s social and economic prosperity
There is hope. The Centre is working to deliver answers by taking an unbiased approach to the neuroscience of Alzheimer’s and dementia.
Our thought leadership
The CNRM has long advocated for different ways forward in Alzheimer’s and dementia research. Professor Bryce Vissel’s legacy in this area is substantial, and he has been leading on this issue for more than a decade. He was one of the first voices in the global scientific community calling for a new approach, because the almost-singular focus on amyloid wasn’t delivering results.
International momentum for a change in methodology has grown in line with this influential, highly cited paper published by Professor Vissel and the Centre.
The amyloid approach has had too much emphasis without enough attention focused on other ways forward. The Centre is addressing this by undertaking research to deliver new insights to this disease.
The power of the Centre’s research is its capacity to bring together UTS’ core disciplines of technology, health and science, accelerating outcomes through multidisciplinary collaboration not only locally, but internationally.
It’s this pioneering approach that the Centre’s using to tackle one of the most serious health challenges in Australia: Alzheimer’s disease and dementia
About Alzheimer’s & dementia – the state of play
Dementia, including Alzheimer’s, is an urgent health crisis. It kills 13,126 Australians a year and in 2018, is estimated to have cost Australia more than $15 billion dollars.
In Australia the number of deaths from dementia, including Alzheimer’s disease, increased by 68 per cent in the last decade – and it is the leading cause of death for women.
Without a medical breakthrough, in the next 40 years approximately 6 million of us will be diagnosed with Alzheimer’s.
Everyone over 65 is at risk. Globally, it affects almost 50 million people.
The amyloid approach?
The field has spent 40 years studying drugs that target amyloid plaque, a substance in the brain, but none of these drugs or related drug trials have worked to treat Alzheimer’s.
In recent times, it has reached a crescendo of urgency. Results were published from the APECS trial, a Phase 3 study of the BACE1 inhibitor verubecestat. The April New England Journal of Medicine reported that dementia progressed faster in patients treated once daily for 104 weeks with the 40mg dose of the drug than it did in those on placebo or the lower 12mg dose. This was despite the drug appearing to slightly decrease plaque load in the brain.
Failing global drug trials
The result represented another devastating setback after a train of high-profile failures of anti-amyloid drugs culminated in the most recent trial failure that had so much hope vested in it. We know the drug hit its target and removed amyloid, but still did not help patients, which makes many of us “very pessimistic that the amyloid approach will work clinically.”
Meanwhile, major drug-makers – including Eli Lilly and Co, AstraZeneca Plc, Roche Holding AG, Pfizer Inc, Merck & Co, and Johnson & Johnson – have abandoned Alzheimer’s drugs targeting amyloid because of lack of efficacy or safety issues. Roche is still testing an amyloid-targeting drug, gantenerumab, at a higher dose after it failed in a trial in early-stage disease.
What is the answer?
The amyloid theory may not be wrong. However, the Centre believes we need to start exploring other options, because we still have no proven way forward for slowing dementia, an insidious disease which robs people of their memories, their identities, and ultimately, their lives.
We believe science is the key to creating a world wherein devastating conditions of the brain like Alzheimer’s can be treated successfully.
The Centre is taking an unbiased approach to the neuroscience: driving plasticity and regeneration; and understanding risk factors like genetics, nutrition, lifestyle and even infection. The Centre also considers the whole-of-person in their cutting-edge research.
We’re working on three different approaches to rescue synapses. We’re:
- Targeting inflammation and promoting nerve rescue
- Directing research towards brain regeneration
- Discovering what the risk factors tell us about the causes of AD, and how we can use this information to develop approaches to slow progression more effectively.
The Centre believes in far more sophisticated ways of understanding neural networks, neural circuits and complex disease causes. Its researchers are working on developing new insights in neuroscience.
Understanding risk factors
We know that there are lifestyle factors that modify risk of dementia, perhaps as much as 35% of the risk.
The Centre is concentrating on this as a starting point, in terms of what the risk factors are telling us, both about the cause and how to stave off the disease.
It’s not controversial to state that there are risk factors for AD that include diet; lifestyle; and social factors like trauma – among others. However there have been relatively few studies assessing whether modifying these risk factors after disease onset can vary or change disease outcomes.
There are two types of risk factors we seek to understand – modifiable and unmodifiable.
Unmodifiable factors include genetics – for example, genes that control immune response; and genes that effect cholesterol.
There is anecdotal evidence for the hypothesis that altering risk factors after disease onset can modify or change disease outcomes. Crucially, the Centre is listening to new theories that are delivering results.
Modifiable risk factors
Modifiable risk factors include lifestyle; maintaining social engagement; and the management of diabetes, depression and obesity.
They also include doing all we can in our thirties and forties to tackle the many risk factors, including vascular health; weight; exercise; diet and metabolic syndrome. These interventions may have the potential to postpone or prevent a third of dementia cases.
If we actively address the various risk factors, we are going to see a major drop in the burden of Alzheimer’s, and an extraordinary change in the current direction of this massive and very tragic health crisis.
The Centre’s research will focus on understanding the risk factors, so we can make prevention and effective treatment a reality.
Synaptic dysfunction & Inflammation
We believe that the key problem in AD is the loss of synapses – connections between nerve cells that we know are important in memory and loss of nerve cells themselves. When the synapses are lost, it impairs memory, behaviour and the way we think.
We think brain inflammation drives synapse loss. The loss of connections between nerve cells in the brain = synapse loss. Question is: what's causing that damage in Alzheimer’s and dementia patients?
Our team of scientists will:
- Transform theories about how inflammatory cells and neurons interact with each other into a better understanding of how inflammation creates a unique cellular environment
- Continue to identify how this cellular environment can be altered to provide substantial therapeutic outcomes
- Provide evidence that inflammation and other processes suggested to be involved in Alzheimer’s and dementia are linked, e.g. inflammation and synapse loss
- Discover the mechanisms and links between inflammation, brain metabolism, infection, neurotrophic factors, and excitotoxicity to identify novel therapeutic approaches;
- Establish the science to study synapses and circuits that underpin cognition. If we can understand how these go wrong in Alzheimer’s and dementia patients, we may be able to leverage that knowledge to drive recovery;
- Progress plans for a clinical program and research effort, including affiliated health workers and medical professionals to provide all-of-person care;
- Involve mathematical modelling, bioengineering, medicine, and allied health (including nursing) in a new truly multidisciplinary approach to solve dementia Alzheimer’s disease; and
- Work to further develop the Centre’s evidence that regeneration can be stimulated in the brain. If proven, this will change the thinking around the possibility of recovery in Alzheimer’s and dementia patients.
The Centre is uniquely positioned to transform, modernise, and accelerate research advances due to its ability to integrate research from multiple disciplines in a way that is only possible at an innovative university of technology.
The Centre can bring together biology, medicine, computation, mathematics, chemistry, physics, cell biology, neuroscience, engineering, and bioengineering to impact knowledge in unprecedented ways.
The Centre can cultivate an environment of innovation and integration across these disciplines to produce truly innovative science.
Care for patients
With links to medical and allied health, the Centre intends to develop an integrated research and education program in all-of-person care for scientists, doctors, nurses, psychologists, physiotherapists, and others in order to help transform patient care, management, and support. It also intends to provide education and support to communities and patients.
The future of Alzheimer’s & dementia research
Professor Vissel and the CNRM are set to deliver transformational outcomes for sufferers of dementia and Alzheimer’s disease.
As the Centre grows and continues its research into dementia and Alzheimer’s disease, it will focus on the areas of slowing nerve cell death, synaptic plasticity, and regeneration, outlined below:
Nerve cell death
- Continue research into the role of kainate receptors in cell death
- Continue to screen potential therapeutic targets in animal models of Alzheimer’s disease
- Leverage the opportunities provided by interaction with departments within the Faculty of Science to make our research truly translatable such as designing and testing of drug compounds.
- Utilise findings that the brain can repair itself after injury
- Determine if this capacity can be stimulated in Alzheimer’s and dementia
Inflammation and glial cells
- It is increasingly shown that synapses play an important role in the overall health of nerve cells and can often degenerate prior to cell death
- Investigate how synapse function changes in Alzheimer’s and the subsequent effects on nerve cells and motor function
- Use high-powered and sophisticated imaging techniques to reveal effects of therapies on synapses.