Dementia Research: A Vision for Australia

Transcription

1 Dementia Research: A Vision for Australia September 2004 The Australia Virtual Group Professor Zaven Khachaturian Professor Henry Brodaty Professor Tony Broe Professor Tony Jorm Professor Colin Masters Professor Rhonda Nay Dr Mukesh Haikerwal Glenn Rees Lee-Fay Low

2 Australia 2 Acknowledgments Australia thanks Lee-Fay Low, the Virtual Group Project Officer, for her work in supporting the Virtual Group and preparing the supporting research paper. Pfizer Pty Ltd supported the employment of the Project Officer through an unrestricted grant. Pfizer had no part in the direction of this project or the content of this statement. The photographs were provided by Lynton Crabb photography. Australia Research Ltd has been established by Australia to fund research projects and, in particular, to stimulate interest among young researchers. If you are interested in contributing to the research efforts of Australia, you can: send a cheque to Alzheimer's Australia Inc at PO Box 108, Higgins ACT 2615 or donate online at s.org.au and follow the links to our secure payment facility. You may specify in the online donation form that your donation is for research. Donations to Alzheimer's Australia are tax deductible.

3 Australia 3 FOREWORD The objective of this Statement is to promote public awareness that, through research, positive solutions will be found to the dementia epidemic. It is vital that Australians understand that progress is being made in discovering effective interventions. It is now within the grasp of science to develop strategies that will delay the onset of the condition and eventually work towards the goal of prevention. We need ways to prevent or delay the onset of dementia and hence to reduce the number of people affected by dementia, the duration of the illness and thus the human and economic cost of care. Australia is delighted that Professor Zaven Khachaturian, the eminent US dementia expert, has accepted our invitation to visit Australia during Dementia Awareness Week in September Professor Khachaturian and members of the Scientific and Medical Panel of Australia and Australia Research have developed this vision statement. In their report The Dementia Epidemic: Economic Impact and Positive Solutions for Australia, Access Economics recommended that the funding of dementia research should form an integral part of the government s response to the dementia epidemic. They recommended that urgent action should be taken to substantially boost the level of funding for dementia research, particularly given Australia s international comparative advantages in quality health research, as well as potentially enormous and cost effective returns. We need to encourage research that is collaborative and multidisciplinary, in areas such as the interaction of dementia with other conditions like diabetes and cardiovascular disease. By supporting centres of excellence and improved networking we can succeed in tackling dementia and the other major chronic diseases. Dr Robert Yeoh President, Australia September 2004

4 Australia 4 DEMENTIA RESEARCH: A VISION FOR AUSTRALIA Why commit to prevention now? Dementia has the potential to become an enormous public health problem in Australia. Interventions delaying the average onset of dementia even modestly would have a major positive public health impact. Current projections are that by 2020 and 2040 there will be, respectively, 270,000 and 500,000 people with dementia in Australia. 1 The financial and social costs of dementia are already significant. Access Economics estimates that the cost in 2004 of dementia is $6.1 billion including $3.56 billion in direct health care costs (mainly residential care costs), around $1.96 billion in family and carer costs, and the remainder in productivity losses, aids and modifications. 2 In respect of disease alone (assuming that accounts for 59% of all cases of dementia), Access Economics 3 estimates that, if from 2005 the average onset of could be delayed by: 5 months, there would be a 5% reduction in new cases each year. This would result in 3.5% fewer cases by 2020 (4,583) and 4.8% fewer cases by 2040 (18,970). 5 years, there would be a 50% reduction in new cases each year. This would result in 35.2% fewer cases by 2020 (46,568) and 48.5% fewer cases by 2040 (96,690)

5 Australia 5 In 2004, assuming that disease costs some 59% of the cost of all dementias, and allowing for increased prevalence due to demographic ageing and cost increases of 2.5% per annum between 2002 and 2004, the cost of disease in Australia is estimated by Access Economics to be $3.6 billion. On the basis of their modelling Access Economics has presented cumulative savings scenarios. If the average onset of disease was reduced by 5 months from 2005, then by 2020 cumulative savings of $1.3 billion would be realized and by 2040, $6.6 billion. If the average onset of disease was reduced by 5 years from 2005, then by 2020 cumulative savings of $13.5 billion would be realized and by 2040, $67.5 billion. The savings in terms of human suffering are immeasurable. These significant potential savings for disease alone are the result of the growth in numbers of people living with disease and the high cost of residential care. Delaying the onset of dementia reduces the number of years lived with the disease and is not likely to increase health burden. disease comprises 50-70% of dementia cases. Vascular dementia makes up another 20-30%, and prospects are even better for preventing this kind of dementia. Vascular dementia incidence has already been reduced in one trial with a high-risk population. Prevention of dementia should be a focus of public health policy and action in Australia. There is no time to lose.

6 Australia 6 Does science have the answers? In the last 15 years, there has been remarkable progress in understanding dementia and improving its management as a result of developments in neuroscience, genetics, medical technology and clinical, nursing and residential care. A review of the state of scientific endeavour and the opportunities it creates in terms of slowing or preventing dementia is attached. In summary, the time is right to launch an initiative that accelerates the needed knowledge to reduce the toll of the human suffering of dementia and the anticipated growth in health costs. What needs to happen now? Within a public health framework, there is a need for a national action plan comprising four elements to prevent or delay the average onset of dementia by 5 years. 1. An increased financial commitment to dementia research This is the critical underpinning of national action. It is proposed that the Australian Government fund a 5-year $250 million dementia research program. $50 million per annum would represent less than 1% of the annual real cost of dementia. Australia should build on its expertise base in molecular biology, neuroscience, genetics, epidemiology, diagnosis, clinical management, consumer support and residential care. There is a need for better Australian data on the actual prevalence in the older age groups for all causes of dementia.

7 Australia 7 Consistent with the existing policy of the Australian Government, there should be an exploration of new methods of research funding such as the USA model of Dementia Research Centres. The multi-factorial nature of dementia research requires multidisciplinary collaboration that is facilitated by a network of State Centres. One of the dilemmas in dementia research is the balance between biological, psycho-social and clinical practice research. There is a tension between the excitement of biomedical research and the slow pace of progress in the development of well-tested and practical strategies to reduce burden of care. With inadequate dementia research funding in Australia, funding for research directed at care is the poor cousin. Some additional research funding should be directed at researching care. 2. Public awareness of dementia Although there is now greater awareness of dementia, there is little understanding of the nature of the condition, its progression and the potential for prevention. There is a need for an ongoing public awareness campaign that sends a strong message that some individuals may be able to reduce their risk of dementia. While there is currently no cure, support for carers, evidence-based care interventions and medications can reduce the impact of the condition for some with a diagnosis of dementia.

8 Australia 8 3. Early diagnosis and intervention Early intervention is important because it enables the person with dementia and their family to plan their finances and future care and to access support and medications. If they have a concern about their memory, 94% of Australians state they would seek advice from their GP. Yet many GPs have difficulty making a diagnosis. There is an urgent need to act on the education and support needs of GPs in the diagnosis and ongoing management of dementia and to design and fund a response to those needs. There is a need to provide more specialist support to GPs by training geriatricians, nurses and other health professionals, building professional networks and using teleconferencing and other forms of e-health to increase access to specialists, streamlined care planning and communication across traditional boundaries. There is an urgent need too for greater consumer access to information and support services. 4. Best practice dementia care Best practice in dementia care is important across the health care system including community, residential, mental health and acute care. There is evidence that well structured carer support including respite, training, counselling and support groups have benefits for both people with dementia and their families.

9 Australia 9 With the shift towards entry into residential care in later stages of dementia, more dementia-specific community care and dementia-friendly day care and residential respite services are necessary. Support services through Australia should also be expanded. The welcome commitment of the Australian Government to introduce a dementia supplement in 2006 as part of new funding arrangements for residential care provides an opportunity to prepare now in determining best practice in the provision of quality dementia care in mainstream residential facilities and dementia specific care units. Training is one important strategy to promote best practice dementia care in both mainstream and dementia specific facilities. It should be compulsory that all aged care staff have minimum qualifications, including dementia-specific training. In addition, more specialist resources are required to service the acute hospital system, the community and residential facilities. Endnotes 1. Access Economics, The Dementia Epidemic: Economic Impact and Positive Solutions for Australia, Australia, Canberra, March Access Economics, Delaying the Onset of Disease: Projections and Issues, Australia, Canberra, August Access Economics (2004), op cit.

10 Australia 10 Members of the Virtual Group Professor Zaven Khachaturian, international consultant on disease and Senior Science Advisor to the Association (US). His former positions include Director of the Office of Disease Research - National Institutes of Health (NIH); Associate Director, Neuroscience and Neuropsychology of Aging Program (NNA) - National Institution on Aging (NIA)/NIH, and Director of the Ronald and Nancy Reagan Research Institute of the Association. Professor Henry Brodaty, Director of the Academic Department for Old Age Psychiatry, Prince of Wales Hospital; Professor of Psychogeriatrics, University of New South Wales; Chairman of Disease International. Professor Tony Broe, Clinical Director, Community Health and Aged Care for Prince of Wales Hospital; Professor of Geriatric Medicine, University of NSW; Scientific Director, Ageing Research Centre, South East Health; National President, Australian Association of Gerontology. Professor Tony Jorm, Director, Centre for Mental Health Research, Australian National University. Professor Colin Masters, Professor of Pathology, University of Melbourne; Chief of Neuropathology and Director of Research Laboratories, the Mental Health Research Institute of Victoria; Consultant in Pathology, Royal Melbourne Hospital. Professor Rhonda Nay, Professor of Gerontic Nursing, LaTrobe University; Director, LaTrobe University Gerontic Nursing Clinical School and the Australian Centre for Evidence Based Aged Care. Dr Mukesh Haikerwal. General practitioner, Australian Medical Association Vice-President. Mr Glenn Rees, National Executive Director, Australia. Ms Lee-Fay Low, Project Officer, Australia.

11 Australia 11 Research Developments towards Dementia Prevention What Does State of the Art Science Say? This paper has been prepared by Australia to support the Vision Statement Summary Scientists are optimistic that preventing onset and slowing progression of dementia are possible. Developments in neuroscience, epidemiology, genetics and medical technology have advanced our knowledge on cause and progression. This knowledge in turn fuels the creation of new treatments. Pathological changes in the brain underlying dementia may begin decades before symptoms manifest. Further, beta amyloid plaques and tangles (hallmarks of brain changes in disease (AD)) have been found in the brains of cognitively normal elderly people 1. Subtle symptoms may occur years before the reason is obvious. Changes in memory can be detected up to 10 years before dementia is diagnosed 2. Research has revealed some of the factors that increase the risk of dementia. Modifying these factors may prevent or delay the onset of dementia. Greater understanding of the neurodegenerative processes involved in dementia has opened avenues for the development of new treatments. Assessment and management techniques have also improved, although much more can be achieved in these areas. Investment in research in dementia needs to be greatly increased in order to reach the critical mass necessary to achieve successful treatment and prevention. Knowledge of modifiable risk factors An important discovery is that vascular disease plays a large role not only in vascular dementia, but also in disease 3. It is theorized that this is because vascular disease causes decreased blood flow to the brain 4. People with heart disease are at higher risk of developing dementia 5-7. Vascular disease appears to have an additive effect with disease pathology. People with disease pathology are more likely to show cognitive symptoms, and decline faster if they also have vascular related brain damage 8,9. Risk factors for vascular disease include high blood pressure, cholesterol and homocysteine, diabetes, smoking and obesity. These risk factors in midlife and beyond have been linked to decline in cognition and risk of dementia There is evidence that lifestyle may influence dementia development. Africans living in Ibidan in Nigeria have lower rates of dementia compared to genetically similar African Americans of similar age living in Indianapolis, Indiana 20. The rates of dementia in Japanese Americans are higher than those dwelling in Hawaii and those rates are higher than in Japanese living in Japan 21. Further, some risk factors vary between different population studies. This could be because of the interaction between different combinations of risk factors and genetic vulnerabilities 22,23. Diet influences risk of dementia. Foods or supplements containing antioxidants or omega- 3 fatty acids have been found to be protective whereas consumption of foods high in total and saturated fat and cholesterol increase risk 29. Activity levels also moderate dementia risk. Higher levels of leisure, physical and mentally stimulating activity in elderly people are associated with lower rates of dementia This is consistent with the protective effect of formal education over and above socioeconomic status 37,38.

12 Australia 12 Developments in Neuroscience It was previously thought that unlike other organs, our brains had their full complement of neurons at birth, and once neurons died they were not replaced. We now know that growth of new neurons and connections between them (neurogenesis) occur in the adult brain 39. Environmental enrichment can increase neurogenesis and improve learning in adults 40. Stem cells occur naturally in the adult human brain. Scientists are working on brain-cell repair treatments that involve introducing growth factors or regeneration support factors to encourage stem cell differentiation and/or injecting stem cells from other parts of the body (e.g. bone marrow or skin) 41. Is Prevention Feasible? We are not yet able to say with certainty if dementia is preventable. We do know there are measures that can prevent stroke and disease of the blood vessels in the brain. And we have evidence of ways to delay, if not prevent, dementia. Public health intervention for modifiable risk factors can prevent or delay dementia onset at the population level. For example, a randomized controlled study of hypertension treatment reduced the risk of dementia by 55% after 4 years 42. Relative risk is the risk of developing dementia of a person exposed to a certain condition or intervention, relative to a person not exposed to that condition. A delay in dementia onset of 5 years can be achieved by an intervention with a relative risk of 0.5 if the risk of developing dementia without intervention is To put this into context, the reported relative risks of developing dementia or disease for a selection of the modifiable factors described above are presented in Table 1. These data demonstrate the large contribution of vascular risk factors and lifestyle to the risk of developing dementia. Population based strategies to reduce heart disease (general screening, dietary interventions, education, pharmacotherapy) have resulted in reduced mortality and cardiovascular risk, and are cost effective 45,46. Unfortunately, many of those studies only included adults under 65 years of age and none examined effects on cognition. Nonetheless such strategies can, and should, be adapted towards dementia delay. New Dementia Treatments under Development There is increasing understanding and knowledge of the neuropathological processes that contribute to the evolution of cognitive decline. Currently scientists are investigating the following mechanisms as potential triggers in the development of neurodegeneration: oxidative stress: when an imbalance between free radical and antioxidant levels results in cell damage 51 mitotic signalling: when cells receive a misleading instruction to replicate, so that they begin to divide, then stall midway leading to cell death 51 inflammation: a natural immune reaction to injury that, when prolonged, can lead to cell damage 6

13 Australia 13 Table 1. Protection conferred by risk factors for disease or dementia Protected group Hypertension treatment for subjects with high BP Comparison group (Relative Risk of 1) Similar subjects receiving placebo Relative Risk Normal midlife blood pressure High midlife blood pressure Normal midlife cholesterol High midlife cholesterol Ibidanian Africans African Americans Weekly fish or seafood eaters Non fish or seafood eaters * Moderate wine drinkers (8 to 14 drinks a week) Users of both Vitamin E and Vitamin C supplements Non-drinkers * Non vitamin supplement users Highest quintile of dietary Vitamin E intake Lowest quintile of dietary Vitamin E intake High leisure activity Low leisure activity High physical activity No physical activity * Frequent cognitive activity (top 10%) More than 2 years of nonsteroidal anti-inflammatory drug users Infrequent cognitive activity (bottom 10%) Non non-steroidal antiinflammatory drug users *indicates that relative risk is for any dementia, not just AD Pharmacotherapeutics addressing these triggers are currently under development and trial in laboratory, animal and human studies. Even when neurodegenerative processes have begun, the symptoms of dementia are treatable. There are currently 4 drugs being marketed for the treatment of AD. These are also under study for the treatment for vascular and Lewy body dementia. Three of these, donepezil, rivastigmine and galantamine increase the amount of the neurotransmitter acetylcholine available in the brain Acetylcholine levels are depleted in AD. These drugs do not modify the disease but may for many individuals delay cognitive decline for a time and improve (or stall decline in) function and behaviour. They also may have long-term effects as they delay nursing home admission 55. The fourth drug, memantine, blocks NMDA receptors. An excessive activation of NMDA receptors is thought to lead to cell death 56.

14 Australia 14 New treatments currently under development extend beyond the symptoms to modifying the progress of dementia. These fall into 3 broad categories 56 : Modulation of known risk factors to prevent progression including lowering blood pressure, cholesterol and homocysteine, reducing oxidative stress, and stroke prevention Increasing growth of connections between brain cells or growing new brain cells to replace those lost, using nerve growth factors, stem cells and drugs that increase neurogenesis Prevention or removal of amyloid plaque formation (particular to the treatment of Disease) using new compounds such as beta and gamma secretase inhibitors, metal chelators and vaccination Assessment and diagnosis There has been substantial improvement in clinical diagnosis of the different dementias. Earlier diagnosis provides benefits for both the person with dementia and the person s family through treatment, support and planning. This will become more important as disease-modifying treatments become available 57,58. Advances in neuroimaging technology: magnetic resonance imaging (MRI), functional magnetic resonance imaging (FMRI), positron emission tomography (PET), and single photon computed tomography (SPECT) provide better methods of examining the condition of brain tissue, and the areas of activation and blood flow in the brain. These tools will improve discrimination between normal ageing and cognitive decline Over 95% of dementia cases result from a combination of factors, including genetics 62. One gene, apolipoprotein E (ApoE), has been consistently shown to confer increased risk of developing dementia. ApoE interacts with lifestyle and health factors such as smoking, antioxidant intake, atherosclerosis and diabetes to increase dementia risk 27, There are numerous candidate genes under investigation 66. In the future, genetic testing may help identify those with high susceptibility for developing dementia. Epidemiological research will help identify additional environmental factors that contribute to dementia. Individuals with more memory decline and cognitive changes than would be expected with ageing are classified as having mild cognitive impairment (MCI). Individuals with MCI have a 3 to 5 times increased risk of developing dementia than others their age 67,68. Studies are underway to improve definition of this preclinical stage of dementia to enable targeted treatment as preliminary evidence suggests that drug treatment can delay progression to dementia 99. General practitioners recognise only between 15% and 42% cases of dementia with better recognition in more severe cases and treat only 7.6% of cases 28,71. This is despite the availability of several screening tests suitable for use in general practice that detect undiagnosed dementia 72,73. After diagnosis, general practitioners have difficulty managing dementia 74,75. Service Delivery and Care There has been extensive development in the areas of management of behavioural symptoms, carer support, residential care provision and staff training. Unfortunately, there has only been limited research producing high level evidence on the best methods of service delivery and care.

15 Australia 15 Assessment and management of the behavioural and psychological symptoms of dementia have improved substantially 76. These symptoms include depression, hallucinations, delusions, agitation and aggression. Certain drug treatments (antidepressants and antipsychotics) and behavioural and psychological approaches (e.g. music therapy, bright light therapy and modification of the physical environment) are effective treatments for these symptoms Dementia care-giving has adverse effects on the psychological and physical health of carers. Psychosocial interventions for carers have been shown to improve psychological morbidity and immune function and delay the person with dementia s admission to nursing home Carers can also be taught to manage behavioural and psychological symptoms 84,85. Caregiver training is as effective as psychotropic medications in reducing agitation in persons with dementia 86. Respite care has become increasingly available 87 and day respite programs benefit both carers and the person with dementia There is increasing evidence that small, home-like dementia-specific units improve quality of life and decrease behavioural and psychological symptoms in residents compared to more traditional nursing home units But appropriate standards of care in such facilities need to be diligently ensured 95,96. Support, education and training for residential care staff in behavioural management techniques result in improvements in the mood and behaviour of people with dementia and decreased staff stress 97,98. References are available in the full document online at

16 Australia member organisations Australia PO Box 108 Higgins ACT 2615 Telephone: Fax: Australia NT PO Box 515 Nightcliff NT 0814 Telephone: Fax: Australia Tas GPO Box 1606 Hobart TAS 7001 Telephone: Fax: Australia ACT Box 108 Higgins ACT 2615 Telephone: Fax: Australia (Qld) PO Box 568 Biggera Waters QLD 4216 Telephone: Fax: Australia Vic Locked Bag 3001 Hawthorn VIC 3122 Telephone: Fax: Australia NSW PO Box 6042 North Ryde NSW 1670 Telephone: Fax: Australia SA 27 Conyngham Street Glenside SA 5065 Telephone: Fax: Australia WA Ltd PO Box 1509 Subiaco WA 6904 Telephone: Fax: Visit the Australia website at for comprehensive information about: dementia and care information, education and training other services offered by member organisations. For further information and advice contact: the Dementia Helpline on or the National Dementia Behaviour Advisory Service on