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THE FLOREY INSTITUTE OF NEUROSCIENCE & MENTAL HEALTH ANNUAL REPORT 2012
Confronting dementia head-on
Why is dementia a global problem?
Confronting dementia head-on ;
Dementia is a growing problem internationally. Here, Associate Professor David Darby, the principal investigator of a major study explores the issue.
Currently it is estimated that there are 35 million people in the world with dementia. Not only is this a staggering figure, but it is predicted to double every 20 years. 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 1 million people by 2050 if the current increase in dementia continues. According to the World Health Organisation, dementia will also overtake both depression and HIV related illness as the leading cause of global disease burden within the next two years. 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?
But aren’t there treatments for dementia? There have been huge advances in the understanding of the molecular, genetic and cellular basis for dementias at the Florey and around the world. 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. Therapies using chemicals found in neuronal signalling 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
Currently there are 150 times more clinical trials focusing on treating people in the late stages of cancer than Alzheimer's disease. One in three people over the age of 65 will die with dementia. More funding for research is urgently needed if we are to defeat the condition once and for all.
British Alzheimer’s Society
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 is 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 These studies, including those detecting individuals who could undergo from our own AIBL study, have the more expensive or invasive diagnostic shown changes up to 30 years techniques mentioned above. In addition, before dementia is diagnosed individuals who are concerned about their memory as they get older can be reassured by regular testing if it shows no such decline.
Age is by far the largest risk factor for dementia. The incidence rises from about one per cent at age 60, doubling every five years. At age 85 years and older, about 45 per cent 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 babyboomers” 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.
Associate Professor David Darby
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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. 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. 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 at the Florey 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 studies, including those from our own Australian Imaging Biomarkers and Lifestyle (AIBL) study, have shown changes up
Research done in Melbourne has shown that about 10 per cent 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. Computerization 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 utilizing 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 6 months prior to 3 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 Dec 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. We are currently recruiting for the TREAD study. Interested participants can learn more about the study by going to the web site at www.tread.florey.edu.au. It is our hope that this sort of effort will help to accelerate the discovery of truly diseasemodifying therapies for Alzheimer’s and other dementias.
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