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Standing Committee on Health and Ageing
Dementia: early diagnosis and intervention

COBIAC, Professor Lynne, Director, Preventative Health Flagship, Commonwealth Scientific and Industrial Research Organisation

MACAULAY, Dr Lance, Theme Leader, NeuroHealth, Commonwealth Scientific and Industrial Research Organisation

Committee met at 11:57.

CHAIR ( Mr S Georganas ): I declare open this public meeting of the House of Representatives Standing Committee on Health And Ageing for the inquiry into dementia, early diagnosis and intervention. Australia's population is ageing and with that has come increased rates of dementia in the community. Nationally it has been predicted that the prevalence of dementia will triple by 2050, making it a significant public health issue. The committee's inquiry intends to focus on how early diagnosis and intervention can play a role in improving quality of life, social and community engagement and future planning for people with dementia and their families.

I would like to take this opportunity to thank the witnesses from the Commonwealth Scientific and Industrial Research Organisation for appearing before the committee. Although the committee does not require you to speak under oath, you should understand that these hearings are a proceedings of the Commonwealth parliament. Giving false or misleading evidence is a serious matter and may be regarded as a contempt of parliament. Please make a brief introductory statement and then we will proceed to questions.

Prof. Cobiac : Thank you very much for the invitation to talk to you. We are looking forward to ongoing discussions. I would like to draw your attention to our submission that we presented to you earlier in the year. That submission relates primarily and specifically to research activity in the space that relates to two areas of your terms of reference for the committee. Those two areas are looking at research that understands early diagnosis of Alzheimer's disease and research into understanding interventions, mainly lifestyle based interventions, and how those lifestyle interventions may help to delay the onset of Alzheimer's disease. To give you bit of background, the submission that you have before you was prepared by Dr Richard Head who was the director of the flagship at that time. He has since stepped aside into another role, and I have been appointed as flagship director as of July this year. I am a bit of the newbie, hence the need for Lance to come along as he has more research details in his head.

CSIRO identified Alzheimer's research as a high priority back in the early 2000s. It set about trying to undertake translational research by developing strong clinical collaborations. With its collaborators it has developed and established the AIBL cohort, the Australian Imaging Biomarkers and Lifestyle cohort. This is a cohort of around 1,000 individuals, including a mixture of people who are normal, people who have mild cognitive impairment and people with Alzheimer's. We have been able to follow that cohort for 4½ years to date. Within that cohort we undertake a range of research. We have brought together a multidisciplinary team that incorporates clinicians, imaging, maths and stats, ICT expertise, psychometrics, lifestyle evaluation—really a multidisciplinary team. The collaborators as part of that are based primarily in Victoria but also in Western Australia. They include the University of Melbourne, National Ageing Research Institute, Austin Health and Edith Cowan University. We also work with the CRC for Mental Health and some industry partners. Major funding sources have come from the CSIRO Flagship Collaboration Fund and the Science and Industry Endowment Fund.

Briefly what have we been doing with that cohort? Our core research can be categorised into five areas. First, mechanistic—so trying to understand the aetiology of Alzheimer's disease and the major contribution of Australian scientists, including CSIRO scientists and its collaborators. Our major contribution in this space is around understanding the role and the structure of the amyloid protein. It is that amyloid protein, once it is deposited in the brain, that can become toxic and cause some of the symptoms that we see with Alzheimer's disease. That is the first core area. The second is around early detection and we know from research that significant brain damage occurs long before clinical signs appear. It is really important that we try and detect Alzheimer's early, before the symptoms appear, so that we can prevent that damage from occurring in the first place. We know that there is something like a 15- to 20-year lag between when people start to have deposits of this toxic amyloid protein in the brain and Alzheimer's becomes more symptomatic. We also know from research that individuals with mild cognitive impairment—so, people who are complaining of memory loss—within five years, what percentage goes through to Alzheimer's?

Dr Macaulay : Of the mildly cognitively impaired people, 80 per cent will go on to Alzheimer's within five years.

Prof. Cobiac : We are really trying therefore to detect the presence of early signs of Alzheimer's before the clinical signs occur. How do we do that? We do that by using advanced imaging technology. That could be through magnetic resonance imaging or through positron emission tomography.

CHAIR: Can you detect those things now through different types of imaging?

Prof. Cobiac : Yes, you can. We are starting to see the emergence of new radioligands, or new dyes, that have a longer half-life and can be more usable in a clinical setting. There is a range of different dyes that can be used to identify the level of amyloid proteins.

CHAIR: Identification is not an issue: we do that now?

Prof. Cobiac : It is an issue in terms of its cost and practical implementation. It is also an issue in terms of understanding the images and reading the images. There is a high degree of skill needed to understand and interpret what we see in those images.

Dr Macaulay : Within Australia it is the ideal research tool currently, the PET detection.

CHAIR: It is not used to diagnose on a regular basis.

Dr Macaulay : It would be used to confirm.

CHAIR: If someone presents to their GP with memory loss, he is not going to send that person off for one immediately.

Prof. Cobiac : They will not as a first line treatment.

Dr Macaulay : They will send you for a neuropsych assessment. That person may elect to send you for amyloid PET imaging, if that is available. Currently that PET imaging is available only in Melbourne. Sydney does not have PET imaging with ligands being used for Alzheimer's disease. The other place it is being done is—

Mr LYONS: Could you explain what 'ligands' are.

Dr Macaulay : Using the PET imaging compound that images the amyloid in the brain can be done in Melbourne. The compound used, the ligand, is available in Melbourne and is also done in Western Australia.

Mr LYONS: Why is it not available where there are other PET scanners?

Dr Macaulay : It is a research tool currently. At this stage dementia clinicians may elect to have it screened for as part of the experimental approach that is being undertaken in Melbourne or Western Australia, at Edith Cowan and the McCusker Charitable Foundation. Those are the two areas. Forty per cent of the cohort is in Western Australia and 60 per cent of the cohort is in Melbourne.

Mr IRONS: What sorts of results are you getting out of the experimental imaging? Is it 90 per cent positive? Are the tests proving that the diagnosis is correct?

Dr Macaulay : What we can say with amyloid PET imaging is that if you do not have a positive amyloid scan you do not have Alzheimer's. The clinician will then go and look for another reason for the dementia: it may be depression, vascular or there may be other causes.

Mr IRONS: Are you saying it is virtually 100 per cent accurate?

Dr Macaulay : If you have amyloid in your brain and you are cognitively impaired, that is a 99 per cent diagnosis.

CHAIR: Prof. Cobiac was making an opening statement. Please hold your questions until she has finished that—I am the biggest culprit—and we will come back to this question.

Prof. Cobiac : Early detection has two main approaches. One is around the imaging—and we have had lots of questions around that. It is also about trying to understand biomarkers and if we can use biomarkers to detect the propensity to develop Alzheimer's early—then that is another form of early detection. Those biomarkers may be present in blood or they may be present in cerebrospinal fluid, so there are two approaches.

CHAIR: So, a spinal tap?

Prof. Cobiac : Yes. So that is our second strand of research. The third strand of research we are doing is investigating interventions. There is no point detecting Alzheimer's early if we do not have an intervention. At this stage we do not have really strong evidence for an effective intervention, and that is part of the big challenge for this research—can we find an intervention that works? There is a lot of activity in the drug space, the therapeutic space, and we have not seen any successful interventions from drugs in terms of curing Alzheimer's. We think that part of the reason for that is that the interventions are starting too late. In my previous comment I said that we start to see the damage in the brain well before the symptoms occur, so what we need to do is undertake an intervention at a much earlier stage—before that damage occurs in the first place.

Dr Macaulay : So a lot of the drug trials have been done with symptomatic Alzheimer's disease to date. Treating non-symptomatic disease is where the trials need to come back towards. Where there is amyloid deposition in the brain of sufferers, and perhaps hippocampal or some volumetric changes in the brain that are indicative of there being some neuron-degeneration in the brain.

Prof. Cobiac : We talked about drug and therapeutic interventions. CSIRO and its collaborators are also looking at the role of lifestyle interventions, and that includes understanding the role of stress, understanding how physical activity may help to delay any further cognitive decline in people with mild cognitive impairment; and also the role of food and nutrition in terms of delaying cognitive impairment. So that is our third area.

The fourth area is combining all of these things, so we have all the information around mechanism, how can we detect it earlier and how can we intervene and therefore prevent the disease from occurring in the first place. So, prevention is a very laudable goal, and we may not be able to actually prevent it, but if we can delay the onset by as few as, say, five, years, then that will have a significant impact both for health and also for the economic status of the health budget.

Dr Macaulay : Around a 50 per cent reductions.

Prof. Cobiac : Our final area is also to contribute on the global stage in terms of contributing to global core indicators. We understand now how important it is to have standardised measures so we can combine data from different cohorts across the world. But, also clinically, we need to have a standardised approach—so cohorts such as AIBL can contribute to that discussion. Our previous submission, the one in front of you, did refer to the RASAD conference, the Research and Standardisation on Alzheimer's Disease conference that was held in Melbourne earlier this year. We have now aggregated those key findings and submitted a paper for publication. We are just awaiting the reviews of that paper as we speak.

CHAIR: Excellent; thank you very much. Was there anything else you wanted to add, Dr Macaulay?

Dr Macaulay : No, I think Lynne has covered it. We will be able to supply the committee with the RASAD paper once it is accepted. We will lodge that with you at that point.

CHAIR: Thank you. We will now go to Ms Hall.

Ms HALL: I just wanted to ask you about the spinal tap. Spinal taps are fairly invasive.

Dr Macaulay : Yes.

Ms HALL: What would be an indicator for you that you would give a spinal tap? Would that be after you had the blood test?

Prof. Cobiac : Remember this is a research study we are talking that.

Ms HALL: I understand it is a research study, but you mentioned spinal taps as a way of identifying Alzheimer's.

Dr Macaulay : Our approach to this would be to try and develop, at this point out of studies such as our AIBL cohort, and some of the other cohorts around Australia—which are leading the world, actually—for example the Memory and Ageing Study, the Older Aged Twin Study and a number of others, and to bring them together. Our primary goal for the AIBL study is to develop an early detection mechanism, which is a population-screening approach using blood.

Ms HALL: But you would not use spinal taps.

Dr Macaulay : No. We would not use a spinal tap and we would not use the PET imaging modalities. We would develop a blood based approach, where we have markers now that have around 85 per cent sensitivity and specificity. They have to be validated against other dementias and we are starting to do that in our studies, to use it as a primary screening approach. A person may have a predisposition to Alzheimer's and would have clinical tests to test their cognitive performance. At that point you would decide to do a spinal tap or PET imaging. Both of those modalities work equally well for detection of Alzheimer's pathology.

Ms HALL: PET imaging is not as invasive but is more expensive.

Dr Macaulay : That is correct. It is being clinically used in one country, but I cannot remember which one it is. It was approved earlier this year for clinical use, for diagnosis.

Prof. Cobiac : It could have a similar approach to what is used for colorectal cancer, for example. You have a bowel-screening test with faecal occult and then you go off and have a colonoscopy. We are thinking that if we can develop a blood based biomarker panel—that is, the initial screen—you can then go off and have the more definitive diagnosis.

Dr Macaulay : Spinal tap is something that can be done in most hospitals around Australia, whereas the PET imaging is only available at a couple of sites.

Mr IRONS: How much use around the world is PET imaging and is it because of the cost or because it is new or experimental that it is only available at two places in Australia? Could you give us an overview on that?

Dr Macaulay : The ligands are only usable for a few hours, particularly the newer ones. GE have developed one with a longer half-life that can be used and shipped across the country. Currently, the ligand is produced in Melbourne and we are just about to try to ship it across to our Perth site of the study to see how it works in those modalities. If it works in that way it could be used at other sites as well and be available for that imaging.

Mr IRONS: Is it used anywhere else around the world?

Dr Macaulay : Yes. Australia is only one part of their study to look at imaging modalities. Australia and AIBL are working to the American ADNI study, which is a large imaging trial that brings together the PET imaging modalities with the MRI imaging to give these answers.

Mr IRONS: Would you say the US is more advanced in the use of that technology than Australia? Are we still in an experimental stage?

Dr Macaulay : No. The AIBL study is world leading in its PET-imaging approaches. In fact, Chris Rowe, who is the Austin lead in this area, is an acknowledged leader for this PET-imaging modality.

Mr IRONS: I have one last question. I just cannot understand why, if we have this technology, we would go from a GP to a neurogeneticist instead of just going straight to PET imaging. We have markers for prostate cancer and all that sort of stuff, so why do we have to go through this process?

Dr Macaulay : It is very expensive to put a person into a PET scanner.

Mr IRONS: It is expensive going to specialists too!

Dr Macaulay : That is true! But it is not something you are going to use as a screen.

Mr IRONS: But if it were me I would want to know—

Dr Macaulay : Also, if people have this amyloid deposition in their brain, we do not know yet that they will all go on to develop Alzheimer's.

Mr IRONS: It is a good indicator, though, isn't it?

Dr Macaulay : Well, it is an indicator. We know from the AIBL study to date that 20 per cent of people in our age cohort, which is people over 70, over a period of three years will go on to develop mild cognitive impairment. But 80 per cent do not. You cannot go and say to that 80 per cent, 'You're going to develop Alzheimer's,' we do not know that yet.

CHAIR: So you are still in that research stage.

Dr Macaulay : Yes.

Prof. Cobiac : Sometimes you might need the other biomarkers to supplement it.

Dr Macaulay : And the value of the cohort studies is really to now say: 'Well, these people have amyloid deposition. How many of those are going to go on to develop Alzheimer's? Is it all of them? How long will it take for them to develop that? Is it 10 years, or five years?' They are the parts of the puzzle that we do not yet know.

Mr IRONS: If you saw that you might try to put some lifestyle interventions in place to prevent it, mightn't you?

Dr Macaulay : Exactly. And the drug trials now are moving back to target people who have this amyloid deposition in their brain, and not dementias.

Ms HALL: So it is looking at reducing this deposition.

Dr Macaulay : Yes. But we know, from the trials to date that have done that with people who have mild cognitive impairment, that it is not early enough. We believe this amyloid is a bit like a rust, if you like.

CHAIR: So, to put a long answer into a short response, I suppose, we still need a few more years to go through those different probabilities to validate them.

Dr Macaulay : Yes.

Mr COULTON: Every time I think of a question you answer it! But if this amyloid is like a rust, does another condition somewhere cause this to form in the first place? I was just about to ask a question, and then you made your last statement. I was wondering whether you are looking at a drug to dissolve this amyloid, or neutralise it or whatever. But is it just a symptom of something else in the brain? Or is it actually the cause of the problem itself?

Dr Macaulay : That is a good question. We do not really know the answer to that. We now believe that the amyloid deposits in the brain are maybe just the rubbish dump for the toxic species of amyloid protein, which is really a smaller molecule. If it aggregates into large clumps of amyloid it forms these deposits, and we think this might be the way the body gets rid of it, actually. That is what we are looking at.

Mr COULTON: Do you think this could be an environmentally caused thing? Every now and then another theory pops up that it is aluminium saucepans, or plastic, or hydrocarbons or something else.

Ms HALL: Or diet.

Mr COULTON: Or diet, or whatever. Is your research showing that this is a natural progression that everyone is sort of on a level pegging for? Or is it something that might have been caused not just by lifestyle? We have heard before that exercise and diet can prevent it, but I am actually wondering about the chemical process itself. Is it a degenerative part of ageing, or is it something that could be caused by external influences?

Dr Macaulay : There is weak evidence that some of our lifestyle things, for example, obesity in midlife, can contribute to it and there is inherited genetic predisposition towards it. A third of the population has ApoE, one of the apolipoproteins, or cholesterol proteins, that are associated with a higher risk—I think it is about two- to threefold higher—of Alzheimer's disease. So there is genetics and there are lifestyle factors as well. Is there environment on top of that? I think that is still a question.

Mr COULTON: Can those lifestyle factors be reversed or is the damage done? If you are obese at 30 and healthy at 40, is the damage done?

CHAIR: Or if you're obese and healthy at 50!

Mr COULTON: We are just getting over the trauma of the obesity inquiry and now we are dealing with this!

Dr Macaulay : That is the value of some of these really long cohort studies that are being done, because they collect all this information and people can trawl over them. If they can bring it together, if the cohorts have been going long enough, they can start to tease out some of these questions. The answer to your question is that currently we do not know.

Prof. Cobiac : What about the role of inflammation?

CHAIR: Did you say 'inflammation'?

Dr Macaulay : Yes, inflammation—diabetes, obesity, metabolic stress and inflammation et cetera. There are indicators that metabolic inflammation and immune disease do contribute to risk and there are trials now being undertaken where drugs that reduce inflammation are actually being used to try to reduce Alzheimer's risk in the elderly population. The answers to that currently are not there.

Mr COULTON: If depression is caused by a chemical imbalance in the brain, can severe depression make one more vulnerable to Alzheimer's and dementia, or are they unrelated? They get misdiagnosed sometimes, don't they?

Dr Macaulay : That is one that I do not know the answer to.

Mr IRONS: As soon as you find out, let us know. We'll let him know!

Dr Macaulay : All right, I will do that.

Ms O'NEILL: Just looking at the young investigator abstracts and the posters in the submission a bit further down the track, there is a lot of important and interesting information that relates to some of the questions we have been asking today. I particularly wanted to ask about the conference that you have had recently. You indicated that there was a gathering following that and there seems to be a real push to get some publication from it, so could you just update us on how things are developing, because it seems from my reading of the material you have submitted that you are right at the cutting edge of this internationally.

Dr Macaulay : That is a good assessment of where we are. We managed to pull together all the world leaders in Alzheimer's disease, with the Alzheimer's Association, which co-led it with us, and we reached consensus on a number of points, including how MRI should be used for Alzheimer's and where the gaps are in how it is used.

Ms O'NEILL: So this was setting up treatment protocols of best practice?

Dr Macaulay : Setting up the stage to be able to progress to that. Currently this is all led by researchers. The concern now is to be able to roll out some of the MRI-type things, for example, into clinical practice, where you have people who are not Alzheimer's experts looking for the MRI changes et cetera that they are picking up.

Prof. Cobiac : In answer to your question, a paper has been prepared and submitted for publication—

CHAIR: Which we will get a copy of?

Prof. Cobiac : which you will get a copy of. Some of the conclusions from that paper we are happy to share with you now—just general conclusions.

Ms O'NEILL: Yes, please.

Prof. Cobiac : Basically, it was recognised how important it was to diagnose Alzheimer's early because of the avalanche of Alzheimer's coming our way. So diagnosing Alzheimer's early is going to be critical as we go forward. We do need the standardised approaches for a diagnosis, but we also need a screening tool so that we do not put everyone through those more intensive diagnosis regimes. It was also recognised that it is an important role for automating analysis of all of the images that are being collected so, as Lance was saying, people who are not the experts can have access to the images and have those subjected to automatic analysis and therefore will come up with consistent evaluations of those images and you do not have to be the expert to have that done if we can start to use those automated approaches. That involves maths, stats and modelling and trying to really look at how we can interpret—

Ms O'NEILL: Teach a computer to see?

Prof. Cobiac : Interpret an image, yes. We need biomarkers that are validated and we can start to use those. It is suggested that we start to use those in clinical settings so we can start to see whether they do have a use in a clinical setting, with the viewpoint of them becoming a screening tool in the future. It was recognised that we still do need research on effective interventions—it could be drug or lifestyle—and how important these cohorts are to supply a platform for answering some of those questions. Basically, as Lance has said, what we concluded is that Australian researchers really are very strong players on the global research stage, if you like, because we are leading the world in many areas in relation to this type of research.

Ms O'NEILL: In terms of international oversight, are there clusterings of dementia that are more prominent in populations, where prevalence is higher, or is it pretty common across the First World at least?

Dr Macaulay : Alzheimer's disease is common across the world, particularly in the First World and increasing in the Third World as people progress to age longer. It is essentially that we are doing so well on so many other fronts that we are living long enough that we get it, therefore we have to do something about it.

CHAIR: It is interesting to see the global evidence. The seat that I represent has the highest incidence of dementia in the country and that is because it has the oldest demographic in the country as well.

Dr Macaulay : To add to Lynne's point earlier, the other key aspect of what the RASAD Conference did come up with was that these cohort studies provide a critical rate of change to the progression of disease measure that there has not been before. With that measure we will be able to look at interventions and see if they are slowing that rate of progression and actually measure the effect of an intervention, whereas currently we do not have the ability to do that very easily with the single points.

Ms O'NEILL: I notice that one of the articles talked about the impact of omega 3s. I wonder if there are sites where we know that cancer is reduced because there are dietary elements that seem to have an ameliorating impact on cancer?

Prof. Cobiac : Do we see the same thing—

Ms O'NEILL: Do you see the same thing with Alzheimer's?

Prof. Cobiac : Do we need to look at that in-depth?

Dr Macaulay : There are studies looking at those sorts of outputs, but we are not there yet.

Prof. Cobiac : We are not sure yet.

Mr WYATT: The issue of gender: is there a bias in respect of men or women? Or is it fairly equal?

Dr Macaulay : There is a slight gender bias. I do not remember which direction it is in. Maybe it is to men, because I do not remember!

CHAIR: It is like everything; they live longer than us.

Mr WYATT: The reason I asked is that we initially considered the amyloid protein—is it consistent in all of your patients or are there variations based on individuals? And if the variations are there, how significant is that in respect of that trending? Because a protein would be a protein, to some extent—

Dr Macaulay : Yes.

Mr WYATT: however, given what we can assume as individuals, our body chemistry and other factors, including the metabolic information, would have to have some impact on a protein?

Dr Macaulay : Yes.

Mr WYATT: And particularly on this becoming a plaque. Are there residual elements within that plaque that distinguish it within individuals?

Dr Macaulay : The plaque itself is actually not what we believe to be toxic in Alzheimer's. The plaque itself is like an endpoint biomarker. We believe that the toxic element is from the smaller amyloid oligomers—smaller proteins—before it actually gets dumped into the plaque. And another protein called tau also misfires and causes neuronal breakdown.

Mr WYATT: I was just going to ask about the plaque: if there is a repository of sediment—and I will use the term 'sediment' loosely—from those two particular proteins you refer to then there would have to be some distinguishing elements for individuals, would there not?

Prof. Cobiac : So would some individuals have more tau than more amyloid, for example?

Mr WYATT: Yes.

Dr Macaulay : Tau and amyloid really follow differently. Some people do load up with more amyloid than others, but I do not think that there is any real discrimination between individuals other than that we know it is higher. I am sorry, I do not really understand the question properly.

Prof. Cobiac : Is there individual variation between—

Dr Macaulay : Some people do have a lot of it—a much heavier load of amyloid.

Mr WYATT: If you have that factor, you would have a variation between individuals?

Dr Macaulay : Yes.

Mr WYATT: But in terms of the protein, is there any variation with the protein between individuals or is the protein consistent for every individual? And is the plaque consistent in its composition in every individual?

Dr Macaulay : The protein is the same with individuals except that there is another form of Alzheimer's, which is an inherited form. It occurs in people earlier, and in those people there are mutations in the amyloid protein that actually account for some of that disease. So they have a slightly different protein that predisposes them to Alzheimer's disease.

Mr WYATT: Which would make the trio look very interesting because you would not have consistency between the two. If it is a chemical ingesture that alters the prevalence or the onset of those proteins, then it will probably require two different treatments?

Prof. Cobiac : I think we might get back to you on this one.

Mr WYATT: That would be good. My only other question is: in terms of all of those in the research trials, are you looking for DNA markers to see if there is an element that switches on the release of those amyloid proteins?

Dr Macaulay : Yes. That has been part of the AIBL study—to take blood and use it to do DNA processing. It is very expensive and we have partnered with large studies in the US to do that sort of analysis over there.

Mr WYATT: Is there any trending showing at this early stage?

Dr Macaulay : There are slight signals but there is not an obvious signal at the moment. The obvious things coming up, like ApoE4 comes up, for example, but not a marked couple of things that will come up. I think it is going to be like diabetes and other things where there will be multiple things that lead to this.

Mr LYONS: I do not want to drag this on, but I wonder about the amyloid protein. Can that be drained by shunting? How would you remove it? Obviously some drug would work on it, but are there any ideas about it? I understand that shunting, draining fluid and stuff, has some success in some patients. Could it be drained?

Dr Macaulay : Once you have actually got the disease, I think it is too late.

CHAIR: The whole idea is to find something to prevent getting it.

Dr Macaulay : Yes. For people who have that deposition and they are cognitively normal, perhaps there might be the opportunity to take that sort of approach. There are monoclonal antibody trials that have all just recently failed—by Pfizer and others—that everybody is very disappointed about, obviously, but perhaps we need to go back a bit earlier with those or put that in train with other treatments such as actually getting at the production of the protein or tackling tau pathology or tackling neuroinflammation itself. I think if we put in some combinations we might be on the way. Those are the sorts of things that have to be trialled through these cohort studies.

CHAIR: It sounds like it is still a long way off.

Dr Macaulay : It is still a way off.

Mr LYONS: Does the research involve the whole of the country? How do you tap into the potential of the whole country?

Dr Macaulay : The CSIRO sees itself as a linker for some of this work. We started this AIBL cohort, which was in neuroscience hub in Melbourne. I was there at a presentation last week and they were led to be the second highest publication level in the world for neuroscience over the last decade, for example. So our neuroscience hub there is good and alive. The other place we work with is Ralph Martins over in WA. We are trying to pull together some of the value out of the memory and ageing study in Sydney. I think that is important. CSIRO have just funded a collaborative project to see if there are ways we can link the AIBL cohort study with the memory and ageing study in some ways. There is also value to be gained out of pulling together another study that CSIRO is involved in, which is an aspirin in ageing study being led by John McNeil from Monash University. It is looking at low-dose aspirin and lowering inflammation levels and seeing if that is protective.

Mr LYONS: I suppose it is improving blood flow.

Dr Macaulay : Exactly, so you have both benefits.

Mr LYONS: The brain goes well with more blood.

Dr Macaulay : The distinction between vascular changes and some of the brain changes is quite close. I would not be separating them quite so much. There is also value in the aspirin (ASPREE) study and bringing them into the cohort. Queensland also has the QUT study.

Mr IRONS: I have two question—depending on the answers. Are there any roadblocks in the research field that this committee could recommend to the government to remove?

Dr Macaulay : That is an interesting one.

Prof. Cobiac : Apart from the obvious one of the challenges with keeping cohorts going—that is a challenge because they are resource intensive and take a lot to keep going.

Mr IRONS: I ask because we visited a research site that had drugs they were testing on mice that they wanted to test on humans. They could not test on humans, because of the ethics until they had proven that they had Alzheimer's. By the time they were diagnosed with Alzheimer's, it was too late to test the drug, so they needed to get the people early in the development stage.

CHAIR: They were preventative drugs.

Mr IRONS: But the ethics said they were not allowed to do that—and it works on mice; it slows down the—

Dr Macaulay : There are a lot of drugs that work on mice that do not work on humans.

Mr IRONS: They do not know that if they cannot test them, do they?

Dr Macaulay : The question is whether they have been used early enough or not. That is a difficult one.

Mr IRONS: So ethics is stopping people researching.

Dr Macaulay : I think it is important to have ethics in place regardless. I would not go anywhere without appropriate ethical—

Mr IRONS: I was just asking. I just see things that I think should be fixed and they are not fixed because—

Dr Macaulay : The major thing, as far as we are concerned, is keeping the value of the cohorts going for the longer term. There is value there currently and it is world leading. The value will increase as they progress further, because you can start to answer some of the questions that you were asking before about what you have done in midlife. If you have got all of that data, you can pull out medication data. There is a lot of interest now in diabetes drugs and how they affect the treatment of Alzheimer's, for example. There are all sorts of things that you cannot do unless you have data that goes back far enough.

Prof. Cobiac : Longitudinal data.

Mr IRONS: That is what is missing in this whole thing over the years to come.

Dr Macaulay : That is what makes the AIBL study so valuable because it is the longest-running study—

Mr IRONS: The subject of Mitochondria Week next week was raised in parliament. During that discussion it was raised that it could contribute to the onset of Alzheimer's. Have you had any tests or thoughts on that?

Dr Macaulay : Mitochondrial power comes down to the metabolic inflammation question again and making sure that you have got the appropriate energy. Mitochondria are your energy store that keeps you going.

CHAIR: Thank you very much for appearing before the committee and giving us valuable information of where you are heading and what the issues are. If there is anything further that we may require, we may call upon you again; and vice versa, for example, if for whatever reason, it was not brought up today and you feel it should be, please feel free to contact us. We are looking forward to the conference paper. That will be a great contribution and help to us. Thank you to the other people who are here, the committee members, and broadcasting for ensuring there is an accurate record of everything that was said today. Thank you also to the secretariat for putting it altogether.

Resolved (on motion by Mr Irons):

That this committee authorises publication, including publication on the parliamentary database, of the transcript of the evidence given before it at public hearing this day.

Committee adjourned at 12:50