dementia research: a vision for australia

Dementia Research:A Vision for Australia

September 2004

The Alzheimer’s 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

Alzheimer’s Australia 2

Acknowledgments

• Alzheimer’s 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.

Alzheimer’s Australia Research Ltd has been established byAlzheimer’s Australia to fund research projects and, inparticular, to stimulate interest among young researchers.

If you are interested in contributing to the research efforts ofAlzheimer’s Australia, you can:

§ send a cheque to Alzheimer's Australia Inc at PO Box 108,Higgins ACT 2615 or

§ donate online at www.alzheimer’s.org.au and follow thelinks to our secure payment facility.

You may specify in the online donation form that your donationis for ‘research’.

Donations to Alzheimer's Australia are tax deductible.


FOREWORD

The objective of this Statement is to promote public awareness that,through research, positive solutions will be found to the dementiaepidemic. It is vital that Australians understand that progress is beingmade in discovering effective interventions. It is now within the grasp ofscience to develop strategies that will delay the onset of the condition andeventually work towards the goal of prevention.

We need ways to prevent or delay the onset of dementia and hence toreduce the number of people affected by dementia, the duration of theillness and thus the human and economic cost of care.

Alzheimer’s Australia is delighted that Professor Zaven Khachaturian, theeminent US dementia expert, has accepted our invitation to visit Australiaduring Dementia Awareness Week in September 2004. ProfessorKhachaturian and members of the Scientific and Medical Panel ofAlzheimer’s Australia and Alzheimer’s Australia Research have developedthis vision statement.

In their report The Dementia Epidemic: Economic Impact and PositiveSolutions for Australia, Access Economics recommended that the fundingof dementia research should form an integral part of the government’sresponse to the dementia epidemic. They recommended that urgentaction should be taken to substantially boost the level of funding fordementia research, particularly given Australia’s international comparativeadvantages in quality health research, as well as potentially enormous andcost–effective returns.

We need to encourage research that is collaborative and multi-disciplinary, in areas such as the interaction of dementia with otherconditions like diabetes and cardiovascular disease. By supporting centresof excellence and improved networking we can succeed in tacklingdementia and the other major chronic diseases.

Dr Robert YeohPresident, Alzheimer’s AustraliaSeptember 2004


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 Alzheimer’s disease alone (assuming that Alzheimer’s

accounts for 59% of all cases of dementia), Access Economics3 estimates

that, if from 2005 the average onset of Alzheimer’s 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)


In 2004, assuming that Alzheimer’s 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 Alzheimer’s 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 Alzheimer’s 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 Alzheimer’s 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 Alzheimer’s disease alone are the

result of the growth in numbers of people living with Alzheimer’s 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. Alzheimer’s 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.


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.


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.


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.


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 Alzheimer’s 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, Alzheimer’s Australia, Canberra, March 2003

2. Access Economics, Delaying the Onset of Alzheimer’s Disease: Projections and Issues,

Alzheimer’s Australia, Canberra, August 2004.

3. Access Economics (2004), op cit.


Members of the Virtual Group

Professor Zaven Khachaturian, international consultant on Alzheimer’sdisease and Senior Science Advisor to the Alzheimer’s Association (US).His former positions include Director of the Office of Alzheimer’s DiseaseResearch - National Institutes of Health (NIH); Associate Director,Neuroscience and Neuropsychology of Aging Program (NNA) - NationalInstitution on Aging (NIA)/NIH, and Director of the Ronald and NancyReagan Research Institute of the Alzheimer’s Association.

Professor Henry Brodaty, Director of the Academic Department for OldAge Psychiatry, Prince of Wales Hospital; Professor of Psychogeriatrics,University of New South Wales; Chairman of Alzheimer’s DiseaseInternational.

Professor Tony Broe, Clinical Director, Community Health and AgedCare for Prince of Wales Hospital; Professor of Geriatric Medicine,University of NSW; Scientific Director, Ageing Research Centre, South EastHealth; 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 ofMelbourne; Chief of Neuropathology and Director of ResearchLaboratories, the Mental Health Research Institute of Victoria; Consultantin Pathology, Royal Melbourne Hospital.

Professor Rhonda Nay, Professor of Gerontic Nursing, LaTrobeUniversity; Director, LaTrobe University Gerontic Nursing Clinical Schooland the Australian Centre for Evidence Based Aged Care.

Dr Mukesh Haikerwal. General practitioner, Australian MedicalAssociation Vice-President.

Mr Glenn Rees, National Executive Director, Alzheimer’s Australia.

Ms Lee-Fay Low, Project Officer, Alzheimer’s Australia.


Research Developments towards Dementia PreventionWhat Does ‘State of the Art’ Science Say?

This paper has been prepared by Alzheimer’s Australia to support the Vision Statement

SummaryScientists are optimistic that preventing onset and slowing progression ofdementia are possible. Developments in neuroscience, epidemiology, geneticsand medical technology have advanced our knowledge on cause andprogression. This knowledge in turn fuels the creation of new treatments.

Pathological changes in the brain underlying dementia may begin decades beforesymptoms manifest. Further, beta amyloid plaques and tangles (hallmarks of brainchanges in Alzheimer’s disease (AD)) have been found in the brains of cognitively normalelderly people1. Subtle symptoms may occur years before the reason is obvious. Changesin memory can be detected up to 10 years before dementia is diagnosed2.

Research has revealed some of the factors that increase the risk of dementia. Modifyingthese factors may prevent or delay the onset of dementia. Greater understanding of theneurodegenerative processes involved in dementia has opened avenues for thedevelopment of new treatments. Assessment and management techniques have alsoimproved, although much more can be achieved in these areas. Investment in researchin dementia needs to be greatly increased in order to reach the critical mass necessary toachieve successful treatment and prevention.

Knowledge of modifiable risk factorsAn important discovery is that vascular disease plays a large role not only in vasculardementia, but also in Alzheimer’s disease3. It is theorized that this is because vasculardisease causes decreased blood flow to the brain4. People with heart disease are athigher risk of developing dementia5-7. Vascular disease appears to have an additive effectwith Alzheimer’s disease pathology. People with Alzheimer’s disease pathology are morelikely to show cognitive symptoms, and decline faster if they also have vascular relatedbrain damage8,9.

Risk factors for vascular disease include high blood pressure, cholesterol andhomocysteine, diabetes, smoking and obesity. These risk factors in midlife and beyondhave been linked to decline in cognition and risk of dementia10-19.

There is evidence that lifestyle may influence dementia development. Africans living inIbidan in Nigeria have lower rates of dementia compared to genetically similar AfricanAmericans of similar age living in Indianapolis, Indiana20. The rates of dementia inJapanese Americans are higher than those dwelling in Hawaii and those rates are higherthan in Japanese living in Japan21. Further, some risk factors vary between differentpopulation studies. This could be because of the interaction between differentcombinations of risk factors and genetic vulnerabilities22,23.

Diet influences risk of dementia. Foods or supplements containing antioxidants or omega-3 fatty acids have been found to be protective24-28 whereas consumption of foods high intotal and saturated fat and cholesterol increase risk29.

Activity levels also moderate dementia risk. Higher levels of leisure, physical andmentally stimulating activity in elderly people are associated with lower rates ofdementia30-36. This is consistent with the protective effect of formal education over andabove socioeconomic status37,38.


Developments in NeuroscienceIt was previously thought that unlike other organs, our brains had their full complementof neurons at birth, and once neurons died they were not replaced. We now know thatgrowth of new neurons and connections between them (neurogenesis) occur in the adultbrain39. Environmental enrichment can increase neurogenesis and improve learning inadults40.

Stem cells occur naturally in the adult human brain. Scientists are working on brain-cellrepair treatments that involve introducing growth factors or regeneration support factorsto encourage stem cell differentiation and/or injecting stem cells from other parts of thebody (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 thereare measures that can prevent stroke and disease of the blood vessels in the brain. Andwe have evidence of ways to delay, if not prevent, dementia.

Public health intervention for modifiable risk factors can prevent or delay dementia onsetat the population level. For example, a randomized controlled study of hypertensiontreatment reduced the risk of dementia by 55% after 4 years42.

‘Relative risk’ is the risk of developing dementia of a person exposed to a certaincondition or intervention, relative to a person not exposed to that condition. A delay indementia onset of 5 years can be achieved by an intervention with a relative risk of 0.5 ifthe risk of developing dementia without intervention is 143. To put this into context, thereported relative risks of developing dementia or Alzheimer’s disease for a selection ofthe modifiable factors described above are presented in Table 1. These data demonstratethe large contribution of vascular risk factors and lifestyle to the risk of developingdementia.

Population based strategies to reduce heart disease (general screening, dietaryinterventions, education, pharmacotherapy) have resulted in reduced mortality andcardiovascular risk, and are cost effective45,46. Unfortunately, many of those studies onlyincluded adults under 65 years of age47-50 and none examined effects on cognition.Nonetheless such strategies can, and should, be adapted towards dementia delay.

New Dementia Treatments under DevelopmentThere is increasing understanding and knowledge of the neuropathological processes thatcontribute to the evolution of cognitive decline. Currently scientists are investigating thefollowing mechanisms as potential triggers in the development of neurodegeneration:§ oxidative stress: when an imbalance between free radical and antioxidant levels

results in cell damage51

§ mitotic signalling: when cells receive a misleading instruction to replicate, so thatthey begin to divide, then stall midway leading to cell death51

§ inflammation: a natural immune reaction to injury that, when prolonged, can lead tocell damage6


Table 1. Protection conferred by risk factors forAlzheimer’s disease or dementia

Protected group Comparison group (RelativeRisk of 1)

Relative Risk

Hypertension treatment forsubjects with high BP

Similar subjects receivingplacebo

0.46 42

Normal midlife blood pressure High midlife blood pressure 0.33 10

Normal midlife cholesterol High midlife cholesterol 0.35 10

Ibidanian Africans African Americans 0.19 20

Weekly fish or seafood eaters Non fish or seafood eaters *0.39 25

Moderate wine drinkers (8 to14 drinks a week)

Non-drinkers *0.39 24

Users of both Vitamin E andVitamin C supplements

Non vitamin supplement users 0.18 26

Highest quintile of dietaryVitamin E intake

Lowest quintile of dietaryVitamin E intake

0.30 27

High leisure activity Low leisure activity 0.62 33

High physical activity No physical activity *0.45 32

Frequent cognitive activity (top10%)

Infrequent cognitive activity(bottom 10%)

0.53 31

More than 2 years of non-steroidal anti-inflammatorydrug users

Non non-steroidal anti-inflammatory drug users

0.27 44

*indicates that relative risk is for any dementia, not just AD

Pharmacotherapeutics addressing these triggers are currently under development andtrial in laboratory, animal and human studies.

Even when neurodegenerative processes have begun, the symptoms of dementia aretreatable. There are currently 4 drugs being marketed for the treatment of AD. These arealso under study for the treatment for vascular and Lewy body dementia. Three of these,donepezil, rivastigmine and galantamine increase the amount of the neurotransmitteracetylcholine available in the brain52-54. Acetylcholine levels are depleted in AD. Thesedrugs do not modify the disease but may for many individuals delay cognitive decline fora time and improve (or stall decline in) function and behaviour. They also may havelong-term effects as they delay nursing home admission55. The fourth drug, memantine,blocks NMDA receptors. An excessive activation of NMDA receptors is thought to lead tocell death56.


New treatments currently under development extend beyond the symptoms to modifyingthe progress of dementia. These fall into 3 broad categories56:§ Modulation of known risk factors to prevent progression including lowering blood

pressure, cholesterol and homocysteine, reducing oxidative stress, and strokeprevention

§ Increasing growth of connections between brain cells or growing new brain cells toreplace those lost, using nerve growth factors, stem cells and drugs that increaseneurogenesis

§ Prevention or removal of amyloid plaque formation (particular to the treatment ofAlzheimer’s Disease) using new compounds such as beta and gamma secretaseinhibitors, metal chelators and vaccination

Assessment and diagnosisThere has been substantial improvement in clinical diagnosis of the different dementias.Earlier diagnosis provides benefits for both the person with dementia and the person’sfamily through treatment, support and planning. This will become more important asdisease-modifying treatments become available57,58.

Advances in neuroimaging technology: magnetic resonance imaging (MRI), functionalmagnetic resonance imaging (FMRI), positron emission tomography (PET), and singlephoton computed tomography (SPECT) provide better methods of examining thecondition of brain tissue, and the areas of activation and blood flow in the brain. Thesetools will improve discrimination between normal ageing and cognitive decline59-61.

Over 95% of dementia cases result from a combination of factors, including genetics62.One gene, apolipoprotein E (ApoE), has been consistently shown to confer increased riskof developing dementia. ApoE interacts with lifestyle and health factors such as smoking,antioxidant intake, atherosclerosis and diabetes to increase dementia risk27,63-65. Thereare numerous candidate genes under investigation66. In the future, genetic testing mayhelp identify those with high susceptibility for developing dementia. Epidemiologicalresearch will help identify additional environmental factors that contribute to dementia.

Individuals with more memory decline and cognitive changes than would be expectedwith ageing are classified as having mild cognitive impairment (MCI). Individuals withMCI have a 3 to 5 times increased risk of developing dementia than others their age67,68.Studies are underway to improve definition of this preclinical stage of dementia to enabletargeted treatment as preliminary evidence suggests that drug treatment can delayprogression to dementia99.

General practitioners recognise only between 15% and 42% cases of dementia withbetter recognition in more severe cases69-71 and treat only 7.6% of cases 28,71. This isdespite the availability of several screening tests suitable for use in general practice thatdetect undiagnosed dementia72,73. After diagnosis, general practitioners have difficultymanaging dementia74,75.

Service Delivery and CareThere has been extensive development in the areas of management of behaviouralsymptoms, carer support, residential care provision and staff training. Unfortunately,there has only been limited research producing high level evidence on the best methodsof service delivery and care.


Assessment and management of the behavioural and psychological symptoms ofdementia have improved substantially76. 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) areeffective treatments for these symptoms77-80.

Dementia care-giving has adverse effects on the psychological and physical health ofcarers. Psychosocial interventions for carers have been shown to improve psychologicalmorbidity and immune function and delay the person with dementia’s admission tonursing home81-83. Carers can also be taught to manage behavioural and psychologicalsymptoms84,85. Caregiver training is as effective as psychotropic medications in reducingagitation in persons with dementia86. Respite care has become increasingly available87

and day respite programs benefit both carers and the person with dementia88-90.

There is increasing evidence that small, home-like dementia-specific units improvequality of life and decrease behavioural and psychological symptoms in residentscompared to more traditional nursing home units91-94. But appropriate standards of carein such facilities need to be diligently ensured95,96. Support, education and training forresidential care staff in behavioural management techniques result in improvements inthe mood and behaviour of people with dementia and decreased staff stress97,98.

References are available in the full document online at www.alzheimers.org.au

Alzheimer’s Australia member organisations

Alzheimer’sAustralia

PO Box 108Higgins ACT 2615

Telephone: 02 6254 4233Fax: 02 6278 7225

Email:[email protected]

Alzheimer’sAustralia NT

PO Box 515Nightcliff NT 0814

Telephone: 08 8948 5228Fax: 08 8948 5229

Email: [email protected]

Alzheimer’sAustralia Tas

GPO Box 1606Hobart TAS 7001

Telephone: 03 6228 8222Fax: 03 6278 9878


Alzheimer’sAustralia ACT

Box 108Higgins ACT 2615

Telephone: 02 6254 5544Fax: 02 6254 2522


Alzheimer’sAustralia (Qld)

PO Box 568Biggera Waters QLD 4216

Telephone: 07 5594 0270Fax: 07 5571 5987


Alzheimer’sAustralia Vic

Locked Bag 3001Hawthorn VIC 3122

Telephone: 03 9815 7800Fax: 03 9815 7801


Alzheimer’sAustralia NSW

PO Box 6042North Ryde NSW 1670

Telephone: 02 9805 0100Fax: 02 9805 1665


Alzheimer’sAustralia SA

27 Conyngham StreetGlenside SA 5065

Telephone: 08 8372 2100Fax: 08 8338 3390


Alzheimer’sAustralia WA Ltd

PO Box 1509Subiaco WA 6904

Telephone: 08 9388 2800Fax: 08 9388 2739

Email:[email protected]/wa

Visit the Alzheimer’s Australia website at www.alzheimers.org.au forcomprehensive information about:Ø dementia and careØ information, education and trainingØ other services offered by member organisations.

For further information and advice contact:Ø the Dementia Helpline on 1800 639 331 orØ the National Dementia Behaviour Advisory Service on 1300 366 448.

dementia research: a vision for australia

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