Confronting Dementia
April 2013
Our search for treatments and cures for dementia is ongoing and is being conducted with a sense of urgency, given the ageing population.
Melbourne is the nation’s capital of medical research and the Parkville precinct is the epicentre of activity. The Florey Institute of Neuroscience and Mental Health is confronting dementia head-on, from fundamental lab-bench science to the use of the latest in imaging technology to observe the brain hidden behind its bony helmet.
Why is dementia an international problem?
Currently it is estimated that there are 35 million people in the world with dementia. Not only is this a staggering figure presently, but it is predicted to double every 20 years. That means 66 million in 2030 and 115 million worldwide in 2050! And even here in Australia the figures are shattering. Whilst there were an estimated 234,000 people with dementia in 2009, this will rise to one million people by 2050 if the current rate increase in dementia continues. According to the World Health Organization, dementia will also overtake both depression and HIV-related illness as the leading cause of global disease burden within the next two years.
And there’s more. These figures are for patients with dementia, which is the most severe stage with more than twice this number of people estimated to be in earlier stages of the disease.
Why is dementia prevalence increasing?
Age is by far the largest risk factor for dementia. The incidence rises from about one percent at age 60, doubling every five years. At age 85 years and older, about 45 percent of survivors will be afflicted by dementia, the majority of whom will have Alzheimer’s disease. And there is an increasing number of us who are in these older age groups, due to a “balloon of baby-boomers” born just after the Second World War. Instead of looking forward to a golden age of retirement, many are quite reasonably concerned about their risk of getting dementia.
But aren’t there treatments for dementia?
There have been incredible advances in the understanding of the molecular, genetic and cellular basis for dementias. In Alzheimer’s disease, accumulation of a brain protein called “amyloid” occurs and it forms components that are toxic to cellular membranes and synapses, and seems to lead to a cascade of cellular events that result in progressive cognitive decline over many decades. Animal models have been used to aid the development of therapies targeting the initiating events in this cascade and many have proven to be promising in preventing the development of subsequent models of disease. And when translated into human trials, therapies that facilitate chemicals used in neuronal signalling (“neurotransmitters”) have shown heartening improvements in symptoms, and are available to patients with dementia.
However, the real challenge has been to find a therapy that prevents or slows the rate of decline in patients with Alzheimer’s disease. Such therapies should work, but so far they have been disappointing or with only modest success, and it has caused a re-evaluation of what could be done to redress this.
Early detection may be the key
One of the most obvious possibilities is that therapies are most effective in animal models when given very early or even before the disease develops. In man, most trials have been in patients with established Alzheimer’s disease when it’s very unlikely any therapy is capable of reversing neuronal loss and other changes. Indeed, some therapies have removed all traces of the abnormal amyloid without practically significant improvement in the patients’ memory or thinking.
So how do we detect people harbouring this very early disease? There are technological solutions that can detect “biomarkers” or abnormalities in living people that reflect brain pathology due to specific dementias. In Alzheimer’s disease, new PET scanning imaging techniques can show the presence of amyloid and other protein accumulations in the brain, and there are also changes in the cerebrospinal fluid that reflect early disease. These biomarker studies, including those from our own Australian Imaging Biomarkers and Lifestyle (AIBL) study, have shown changes up to 30 years before dementia is diagnosed. Although there are some novel research efforts currently aiming to use these to find high risk individuals, these techniques are probably not suitable for wide scale screening, being too expensive or with significant potential risks (e.g. radiation or infection).
Cognitive screening using the internet
One of the earliest known changes in Alzheimer’s disease is declining memory. Persistent decline in memory is not healthy, but it’s also not specific for Alzheimer’s disease, and can be caused by anxiety, depression, medical, neurological or other causes. But it can be used to flag individuals who might need more detailed assessment. Hence, regular testing of memory is a possible strategy for detecting individuals who could undergo the more expensive or invasive diagnostic techniques mentioned above. In addition, individuals who are concerned about their memory as they get older (and frankly that’s almost all of us) can be reassured by regular testing if it shows no such decline.
Research done in Melbourne has shown that about 10 percent of people over the age of 50 years may show persistent decline in memory, and about half of these will show Alzheimer’s disease pathology on biomarker imaging studies. Hence, such surveillance with cognitive tests is a potentially useful initial screening process. Computerisation of these not only makes it possible to detect subtle changes in memory (often before the individual is aware themselves), but also to serve these to individuals remotely using modern web-browsers. This is the approach of our own TREAD (“Trajectory-Related Early Alzheimer’s Database”) study being conducted at The Florey utilising technology developed by a Melbourne based company, CogState Ltd.
The TREAD Study
This study is currently enrolling people aged 50 years or older who are willing to test their memory and thinking using their own computer and web-browser. They are asked to consent, register and test themselves without supervision at monthly intervals for about six months prior to three-monthly testing. They also are required to provide the contact details of their local medical practitioner and to agree to being informed if they are found to have decline in their memory or thinking. The study started recruiting in December 2012, and with minimal publicity has attracted about 600 participants who have helped us to understand the issues of such an endeavour. We will aim to recruit at least 10,000 participants over the next few months. Participants that show decline in their memory will be offered medical evaluation and if suitable, enrolled in therapeutic trials which involve performing the newer biomarker studies. In this way, we hope to cost-effectively identify individuals with very early Alzheimer’s disease pathology and more importantly offer them involvement in clinical trials of promising therapies aiming to slow the rate of decline and in future prevent progression to dementia.
So, we are currently recruiting for the TREAD study. Interested participants can learn more about the study by going to the web site at tread.florey.edu.au. It is our hope that this sort of effort will help to accelerate the discovery of truly disease-modifying therapies for Alzheimer’s and other dementias.
The Florey Institute, Melbourne
Fast facts:
• The Florey Institute of Neuroscience and Mental Health is home to 590 staff making it the largest brain and mental health research team in Australia and the fifth largest internationally.
• The scientists are answering the big questions about the brain – diseases, mental illnesses and trauma.
• Stroke is a main research area.
• Epilepsy, multiple sclerosis, depression, schizophrenia, addiction, Parkinson’s, Alzheimer’s and motor neurone disease are other major areas of research.
• The Parkville-based institute is fourth in the world for its citation record – the number of times other scientists quote their work – a great benchmark for the quality of research.
• The Victorian Brain Bank Network is based at the Florey, storing 1009 donated brains for research into Alzheimer’s motor neurone disease, schizophrenia and bipolar disorder.
• The scientists work side-by-side with clinicians from Austin Health and the Royal Melbourne Hospital as well as collaborating with 32 countries.
Donations are gratefully accepted. Please call: 03 8344 9679
or visit florey.edu.au.
Australian mental health: state of the nation
• One on five Australians has a brain disorder, highlighting the need to ease the suffering of patients and families.
• About 45 percent of Australian adults will be affected by mental illness at some time in life.
• Three percent will be seriously affected.
• Some 3.2 million Australians each year live with a mental health difficulty.
• Stroke is the second biggest killer of Australians. Some 50,000 had a stroke last year and 420,000 people are survivors of stroke but many are left with disabilities.
Associate Professor David Darby, PhD FRACP, is Principal Investigator, TREAD Study at The Florey Institute of Neuroscience and Mental Health.