Professor Kaarin Anstey
If we’re talking about Alzheimer’s disease, there is a known genetic risk factor that has a known increased risk associated with it. So if you were tested for that, you could say that you have an increased risk. But, at the same time, we know many people live a full life with this genetic risk factor and don’t ever develop Alzheimer’s disease. So it’s not a sentence to find out that you have that risk. And, at the same time, there are people who don’t have that genotype, who do develop Alzheimer’s disease. So, even when we’re looking at genetics, it’s not possible to say to an individual, you will definitely develop Alzheimer’s disease. All we can do is talk about whether you have characteristics that increase your risk relative to the population, but we could never say for the individual, your personal risk is this, because there are so many other complicating factors.
So the example I like to use is smoking and lung cancer. We know that if you smoke you’ve got a greatly increased risk of lung cancer, and of dying of lung cancer. But there are people who develop lung cancer who never smoke, and there are smokers who never develop lung cancer. There are also people who have a genetic risk factor for lung cancer and that can increase their risk, or if they have that genetic risk factor and they smoke, they’ve got a greatly increased risk of developing lung cancer. And it’s pretty much the same with Alzheimer’s disease. The things that we know increase the risk of Alzheimer's disease, apart from your genetics, the biggest risk factor is age. There’s nothing we can do about age.
So, if you wanted to assess your risk, there are a few tools that are available to assess risk. You can do some self-report risk assessment. We've developed an online self-report risk assessment tool at the ANU, that can give you feedback on your risk profile for Alzheimer's disease, and tell you if you’ve got things you can modify to reduce your risk. And there are some clinical assessments that have been used in clinics, particularly in the United States where people have developed a clinical risk assessment for midlife adults, or that have developed in Finland where they can check things like high cholesterol, high blood pressure and so forth, and they give you a score. It’s not as advanced as the field of heart disease, so in heart disease you can go and you can get a Framingham Risk Score done which will tell you your risk of developing heart disease in the next 10 years. We’re not at that point in dementia research; we haven’t been able to pin it down to a time period. We do have risk assessment, but we need the research to develop to get us to that level, the specificity of diabetes and heart disease.
What we did at the ANU was we did those meta-analyses that I’ve already discussed and also looked at published meta-analyses in the literature, and we created a risk assessment algorithm based on the best available evidence at the time for all of the factors known to increase the risk of Alzheimer's disease. So we developed the algorithm and we have risk and protective factors in our scores, so some things actually reduce your risk, and then we developed a questionnaire that assesses each of those risk factors. And the questionnaire is comprised of subscales which are taken from the epidemiological studies that actually linked that exposure to dementia. So, for example, cognitive engagement has been linked to the risk of dementia in two studies, and we use the actual questionnaire that was used in those two studies in our scale.
And that’s another issue around measurement. So one study might find something, but if you use a different questionnaire you may not find the same result. So all the measures that we’ve used in our questionnaire have been linked to dementia. And then we’ve made that available online; it’s free to the public, anybody can assess their own risk and then we provide feedback on what you could do to modify that risk.
So it’s at a fairly general level, because this is a publically available website, it’s not a medical clinic, and it doesn’t involve any medical tests. So, for example, we don’t test your blood pressure, which you’d need to have done by your GP. If you’re really concerned, you can print out a PDF of your assessment that we’ve created, and you could take that to your GP. Otherwise, it gives you fairly general information about risk reduction, but you can get much more detailed information from other websites or from your local doctor.
So with our risk assessment tool, it focuses on understanding your risk, not telling you you’ve got this percentage or that percentage risk of developing Alzheimer's in so many years, and I think it’s important to know your risk profile so you know what you can modify. And then you can change it in time to prevent that risk factor impacting on your brain. People say to me quite often, oh, I just wish I could find out accurate information about what I can improve in my lifestyle to reduce my risk of dementia.
We don’t have a single blood test or medical test that will directly tell you your risk of developing Alzheimer's or another type of dementia. There’s a lot of research ongoing at the moment that’s trying to develop blood tests, and you might see things in the media about research results, but so far there’s nothing that’s been validated and rigorously tested and released onto the market.
Dr Shannon Klekociuk
Coffee is a drink that many of us enjoy and, as most of us know, the main ingredient in coffee is caffeine, a stimulant that excites the nervous system and is responsible for that pick-me-up feeling. Scientists have known for a long time that caffeine can provide us with a short boost to our attentional processing, as well as our memory. So it seems logical to think that something that helps our cognition might actually be beneficial for diseases that impair our cognition.
Some studies have observed coffee drinkers over a long period of time and found that moderate coffee consumption may be associated with reduced dementia risk.
Unfortunately, this finding has not been consistently replicated. Other researchers have suggested that it might be the caffeine itself, rather than the coffee, that is beneficial to reducing dementia risk.
However, a recent meta-analysis, looking at many of these observational studies, was unable to reliably link caffeine consumption with a reduced risk of developing diseases like Alzheimer’s.
It is important to remember that coffee is a stimulant, and that too much coffee can have major ramifications for your health. Overall, its status as a protective factor against diseases like Alzheimer’s remains unclear, and certainly it represents an area where more research is needed.
Dr Shannon Klekociuk
Turmeric is a plant, the root of which can be dried and used as a spice in food, or in alternative medicine.
The main ingredient in turmeric is curcumin, and curcumin is thought to have anti-inflammatory properties which may help alleviate some of the inflammation that occurs in the brains of people with Alzheimer’s Disease. It’s also been suggested that curcumin may help prevent the burden of amyloid protein in the brain, in diseases like Alzheimer’s.
It has also been suggested that curcumin might help prevent the amyloid protein from clustering into plaques in the brain of those with Alzheimer’s Disease. Unfortunately, many of these findings are based on limited animal studies.
Observational data from countries like India have reported a lower incidence of diseases like Alzheimer’s. Some have suggested that this may be due to the relatively high consumption of turmeric. However, it is important to note that differences in life expectancy and the health system may contribute to this finding.
There is no evidence to date that suggests that consuming turmeric will be beneficial for either reducing your dementia risk or treating diseases like Alzheimer’s.
Professor Kaarin Anstey
At a general level, we would say now that what is good for your heart is good for your brain. The vascular risk factors, things that influence your heart health or your vascular system, will also influence your vascular system in the brain, your cerebrovascular health. For example, hypertension is a risk factor for heart disease but it’s also a risk factor for stroke and for dementia.
High cholesterol in midlife appears to, although we don’t have as robust evidence as we’d like on that, but from the evidence we do have, it seems to increase the risk. Diabetes, type 2 diabetes and type 1 both increase the risk. Sedentary lifestyle increases the risk, depression increases the risk. And depression is actually a cardiovascular risk factor, and very much linked with heart health, although it’s sometimes not considered a cardiovascular risk factor in the same way.
We focus on the two most common types of causes of dementia, we have vascular dementia and Alzheimer's disease. Vascular dementia is caused by small strokes and large strokes and through hardening of the arteries. The risk factors that increase blood pressure and cause arthrosclerosis, they’re all going to increase the risk of vascular dementia. But, similarly, what’s being discovered more and more is that the vascular risk factors also increase Alzheimer's pathology in the brain. We don’t understand all the mechanism underpinning that, but they seem to increase that at the same time.
Professor Velandai Srikanth
When we talk about cardiovascular disease, we’re referring to major disease such as having strokes, or heart attacks, or having heart failure. Our research has clearly shown that people who have strokes, heart failure or heart attacks are at very high risk of dementia in the future. Strokes can directly destroy brain cells and hence reduce the capacity of the brain to withstand other insults that might occur in the brain later on, such as Alzheimer’s Disease. Now, while these major events are important in increasing the risk of dementia, it must be kept in mind that the risk factors that lead to these diseases are also important. So, by controlling risk factors such as high blood pressure, diabetes, cholesterol, maintaining activity, stopping smoking; these can all reduce the risk of major cardiovascular disease and, by that, reduce the risk of a future dementia.
Blood pressure tends to increase first as people reach middle age, so middle age is between 40 and 60 years of age. At this point in time, control of blood pressure is likely to reduce the risk of brain injury later on, so one advocates the careful monitoring and control of blood pressure during middle age. But as one gets older and gets a bit frailer so, for example, those in their late 70s or 80s might have difficulty walking, might have poor balance, can have a risk of falling; in such people we are a bit more careful about how aggressively we treat their blood pressure. As one gets even older, blood pressure drops and tends to go down to the lower side of things in some people. Hence at that age, it is quite important to maintain blood pressure at a reasonable level so they can actually function well, and such people we don’t tend to put on high doses of blood pressure reducing medication or even sometimes take them off blood pressure reducing medication.
The relationship between body weight and dementia is quite complicated. As people develop dementia in older age, they tend to lose weight because the brain is probably telling them not to eat much, in some fashion, and hence they lose not just body weight but muscle weight as well. So the risk or the association between body weight and dementia is different in older people compared with younger or middle aged people. In contrast, if you look at middle age, having greater levels of obesity is associated with the risk of dementia in the future. For example, people who have a very large waist circumference, what we call central adiposity, more fat around their hips, tend to have a higher risk of dementia. Such fat can be a source of chronic inflammation and this can affect blood vessel health and brain health directly. So treatment of adiposity or obesity in middle age should be quite aggressive, and can potentially reduce the risk of dementia in the future.
People with advanced dementia tend to lose weight. We don’t know exactly why this happens, but it is probably as a result of the hunger centre in their brains becoming different in the way it acts, so their appetite and their desire for food goes down and we can’t exactly work out, or haven’t been able to work out until now, how to offset this. Research is under way to try and understand what parts of the brain are signalling to stop hunger from happening in people with advanced dementia.
So in people who have already developed strokes or heart attacks, it is still not too late to make a difference to their risk of dementia in the future. We found in our studies that having one stroke by itself may not increase the risk of dementia too much, but having more than one stroke clearly increases the risk of dementia. So, in people who have had a stroke, it is important to do everything you can, with the help of your specialist, to try and have treatments in place that reduce the risk of a further stroke. Now this might mean having blood thinning medications, anti-coagulant medications such as Warfarin, blood pressure reducing medications, and controlling your diabetes. Apart from this, stopping smoking and increasing physical activity are also important. Again, if you haven’t developed major cardiovascular disease, but have risk factors such as high blood pressure and diabetes, it is still not too late to make a difference. In fact, the earlier we treat people before they develop cardiovascular disease, the better it is. So control of blood pressure during mid-life and early older life, control of diabetes, again stopping smoking, increasing your physical activity, reducing your weight, are all important things that need to be aggressively done during middle life.
It is very important to treat vascular risk factors to prevent major cardiovascular disease, and by that I mean preventing strokes and heart attacks. We know that preventing strokes reduces the risk of dementia, and we know that preventing heart attacks reduces the risk of heart failure, which is a risk factor for dementia.
There are a lot of studies currently under way trying to find out if reducing blood pressure or diabetes by themselves can reduce the risk of future dementia. The difficulty with planning studies of this nature is that they require very large numbers of people to participate in these studies, and a very long follow up to see if they do develop cognitive impairment or not. We need to wait for the results of these studies to come out before we can conclusively say which way the evidence goes.
The most important focus needs to be on identifying people who are at highest risk of dementia and trying to design studies to intervene in such people. For example, people with clusters of vascular risk factors such as diabetes and hypertension could be most at risk of dementia, and trying to develop medications, or other lifestyle interventions, in such people will provide the maximum benefit in future dementia reduction.
Professor Velandai Srikanth
There is very good evidence from longitudinal or long term large studies - more than ten such studies have been performed until now - confirming that type two diabetes is associated with a twofold increase in the risk of dementia. More recently, there have been large studies performed in the United States confirming that type one diabetes is also associated with an increased risk of dementia, in a similar twofold increase in the risk of dementia.
So type one diabetes is an important disease, affecting mainly younger people, and in such people, there is difficulty in controlling their blood sugar within a good range of blood sugar, with the treatments that we have. They are more prone to have very low blood sugar, and those people who have more than one episode of low blood sugar can have damage to brain cells or the white matter, which is the wiring connecting brain cells. Annually, about 30% of people with type one diabetes have low blood sugar episodes or hypoglycemia. Any more than four such episodes in a year can be associated with a very high risk of cognitive impairment, or slowing of brain function, and, as such people get older, it is possible that this reduction in cognitive function lowers their brain capacity to withstand other insults to the brain. So, as they get older, they become more prone to the risk of dementia.
Type two diabetes can increase the risk of dementia by affecting health of blood vessels in the brain and the health of neurons, which are the brain cells. In type two diabetes, the cells of the brain are resistant to the action of insulin, and insulin is quite an important chemical in the brain to allow other chemicals to talk between cells. So this might be one way in which type two diabetes affects cognitive function. Another way insulin can be important is to affect the transport of a substance called beta amyloid, which is known to be important for the development of Alzheimer’s Disease. So insulin resistance in cells of the brain can, theoretically, be involved in the deposition of plaques in the brain due to beta amyloid.
In people with type two diabetes, we found that the levels of a protein called tau is increased in the spinal fluid of patients. Tau is an important protein for neuronal health and, if we find increased levels in spinal fluid, it means that nerve cells are being damaged. It is possible that diabetes causes a low grade chronic inflammation in nerve cells, and this might provoke their death.
So, in summary, the effects of type two diabetes on the brain can be a combination of causes. It can be due to the effects of vascular disease and also due to the effect of neuronal death, or what we call neurodegeneration. Although Alzheimer’s Disease is associated with the development of amyloid plaques, it is not clear whether diabetes is a provocative factor in the development of plaque definitely, and further research or investigations are currently happening to try and work this problem out. While type two diabetes increases the risk of dementia overall, it is not clear whether everyone with type two diabetes will develop dementia, and we’re trying to work out in our research who might be more prone to do so.
Pre-diabetes is an important condition that’s been recognised in the last 10 years or so. When we diagnose diabetes, we require a plasma or blood glucose level of 7 millimoles or greater. It has now been recognised that people with blood levels of glucose of about six millimoles are also at risk of complications of diabetes, and will be developing diabetes within the next 10 years. The important thing about pre-diabetes is that it is a preventable condition. Now more recently, studies from the United States have shown that those with pre-diabetes can be at fourfold risk of dementia in the future. Mechanisms by which this might occur are not quite clear, but it is important to realise that, if we treat and prevent diabetes - exercise and diet are important interventions that can help people with pre-diabetes and stop them from developing diabetes in the future - it is possible that such lifestyle interventions can also reduce the risk of dementia in such people.
In people who have pre-diabetes or diabetes, attending your practitioner or specialist on a regular basis, having your medications regularly, making sure that your blood sugar is well controlled but not too aggressively controlled, making sure that your blood pressure is treated effectively and your cholesterol levels are watched carefully; all these things could have an impact on your future health and the risk of dementia, possibly by reducing the risk of vascular disease going into the future.