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Simon Lovestone

Cycling Down Dementia: Simon Lovestone bikes to receive knighthood

Professor Simon Lovestone, Informatics and Digital Health theme lead at the NIHR Oxford Health Biomedical Research Centre, is cycling down to Buckingham palace tomorrow (07/12) to receive a knighthood for services to neuroscience research. He chose the unusual mode of transportation because he is raising funds for the charity Alzheimer’s Research UK, by cycling 300 miles over three months.

Earlier this year, Professor Lovestone was knighted in the Queen’s Birthday honours, and he will be formally receiving the knighthood from a member of the Royal family tomorrow at Buckingham Palace.

Professor Lovestone and his colleagues at the NIHR Oxford Health BRC are aiming to cycle 300 miles apiece over 3 months, as part of the Alzheimer’s Research UK’s ‘Cycling Down Dementia’ fundraising challenge. The charity specialises in finding ways to prevent, treat and cure dementia, and relies on donations to fund vital dementia research.

Professor Lovestone says:

“My research group and I spend all our working lives chasing down dementia – trying to understand this dreadful disease and find treatments to prevent it. So Cycling Down Dementia is a real pleasure and we are delighted to be helping to raise funds for research being done by brilliant scientists all over the UK. I am humbled by being honoured in this way. In truth it is a measure of the good fortune I have had to have had inspiring teachers and wonderful students and to have had the privilege to work together with outstanding scientists in Oxford, across the UK and indeed the world has been the most rewarding gift imaginable. I shall be thinking of those I have known, relatives and patients, with dementia as I kneel tomorrow.”

Donations can be made at https://cycling-down-dementia-the-pioneer-challenge-300-miles.everydayhero.com/uk/simon-s-chasing-dementia, and people can sign up for their own Cycling Down dementia challenge at www.cyclingdowndementia.org.

dolphins

Dolphin brains show signs of Alzheimer’s Disease

A review led by Professor Simon Lovestone, theme lead at the NIHR Oxford Health Biomedical Research Centre, has found the first unambiguous signs of Alzheimer’s disease in a wild animal.

“It is very rare to find signs of full-blown Alzheimer’s Disease in non-human brains,” said Professor Lovestone, who is a researcher within the Oxford University Department of Psychiatry and is the Informatics / Digital Health theme lead at the NIHR Oxford Health BRC. “This is the first time anyone has found such clear evidence of the protein plaques and tangles associated with Alzheimer’s Disease in the brain of a wild animal.”

Like humans, dolphins are almost unique in living long after they are capable of having children. Most animals tend to die shortly after the end of their fertile years.

In a study published in the journal Alzheimer’s and Dementia, researchers tested the idea that living long after the end of fertility might be linked to Alzheimer’s Disease.

The team (which included scientists from the Universities of St. Andrews, Edinburgh, Florida, and Oxford) found signs of Alzheimer’s Disease in the brains of dolphins which had died after washing up ashore on the Spanish coast.

The team think that humans and dolphins are near-uniquely susceptible to Alzheimer’s Disease because of alterations in how the hormone insulin works in these species. Insulin regulates the levels of sugar in the blood, and sets off a complex chemical cascade known as insulin signalling.

Professor Lovestone:

We think that in humans, insulin signalling has evolved, with the effect of prolonging lifespan beyond the fertile years, but it also leaves us open to diabetes and Alzheimer’s Disease. Previous work shows that insulin resistance predicts the development of Alzheimer’s Disease in people, and people with diabetes are more likely to develop Alzheimer’s.

“Our study suggests that dolphins and orcas (who also have a long post fertility life span) are similar to humans in many ways,” says Professor Lovestone. “They have an insulin signalling system that makes them an interesting model of diabetes, and now we have shown that dolphin brains show signs of Alzheimer’s identical to those seen in people.”

Professor Lovestone now hopes to use this understanding to improve the way we test new drugs for Alzheimer’s Disease.

Media coverage

Dementia in dolphins could give clues to Alzheimer’s in humans, The Times, 25/10/2017
Researchers at the University of Oxford have found that dolphins can develop Alzheimer’s disease. ‘It is very rare to find signs of full-blown Alzheimer’s disease in non-human brains,’ said Professor Simon Lovestone. The team suggests that changes in insulin signalling may play a role in triggering Alzheimer’s.

Preventing dementia: how hard can it be?

Simon Lovestone, Professor of Translational Neuroscience, Department of Psychiatry, University of Oxford;
Theme lead for Informatics and Digital Health at the NIHR Oxford Health Biomedical Research Centre

Every morning I see a candidate for prevention of Alzheimer’s disease. He wakes, washes, gets dressed, has breakfast and goes to work. He’s fine; for now. He is a candidate for prevention for only one reason – he is in his mid 50’s.

Alzheimer’s disease creeps up on us so slowly that the amazing capacity of the brain to adapt means we literally do not notice. Research has shown that this period – when the process of Alzheimer’s pathology has started in the brain but there is no apparent effect on the person – lasts for 10, maybe even 20 years. We call this the preclinical period. Given that Alzheimer’s disease becomes common after people reach their mid 70’s, then the man in his 50’s who I live with may just be beginning to have the very first changes in his brain, even if he doesn’t know it.

This very long preclinical period is both an enormous problem and, potentially at least, an astonishing opportunity. The problem is that by the time dementia sets in, the disease has been present for such a long time that it may be too late for most drugs to work. The flip side is that if we could intervene in this preclinical stage, then we might have a chance of slowing down dementia or even reducing the chances of it affecting the person at all. Such intervention is called secondary prevention, to distinguish it from prevention to stop the disease process starting at all.

The trouble with secondary prevention studies

So some questions then – how will we identify people with signs of preclinical disease, and what will we use to prevent them from developing Alzheimer’s? Just how hard is it going to be to do secondary prevention studies?

Take the man I live with as an example – could he enter a study for a secondary prevention intervention? We would need a way to see if he has the very early signs of disease in his brain. In fact, we have neuroimaging scans that can measure the amount of amyloid and tau proteins in the brain; both features of Alzheimer’s. We can also measure these proteins in the fluid that bathes the brain – cerebrospinal fluid (CSF). These tests are however time consuming, uncomfortable and expensive, and relatively few people who take the test turn out to have preclinical dementia.

Not only that, but if someone enters such a trial, how do we know if the secondary prevention intervention has worked? We cannot measure symptoms because the person doesn’t have any. So all we can do is wait to see if the person develops dementia. And because the preclinical period can last 10 years or more, that can be a very long time.

Identifying preclinical dementia

My own research has focused on trying to overcome these two problems.

To identify people who might be in the very early stages of preclinical disease, we have, in the past five years, examined the blood of more than a thousand research volunteers for proteins that are altered when the brain shows some signs of preclinical disease. Excitingly we have found such proteins and developed a way to test for them.

We have a lot of work to do yet – we need to turn our complicated test into something simpler and more stable, we need to replicate again and again, and we need to work out exactly how accurate a predictor the test is. But the progress has increased in pace, and it’s just possible we could be using protein blood tests as part of clinical trials for prevention in the next year or two.

Measuring whether secondary prevention works

The second problem we are now tackling is the tricky one of how to find out whether a preventative intervention is working if there are no symptoms to measure. We wondered if there might be some subtle sign in the way the brain works that we could measure instead.

In the Deep and Frequent Phenotyping study, funded by MRC and NIHR, we are going to do neuroimaging and CSF tests, but then also measure brain structure with MRI and brain function with functional imaging and electrophysiology. Not only that, we will measure everything we can in blood and urine and look in detail at the retina. We will also use devices, including smartphones, to measure memory, behavior, gait and more. We will measure all these things repeatedly over a year, so we will be able to see what changes in people who develop preclinical disease.

Accelerating secondary prevention studies

With these two approaches, we hope to make it possible to do secondary prevention trials quicker and more effectively. With our blood test, we hope to be able to identify people who are more likely to have preclinical disease. And with the Deep and Frequent Phenotyping study, we hope to find a test that would be able to say whether a secondary prevention intervention was having an effect or not.

Which of course begs the question – what interventions could we use for secondary prevention? Here scientists are not short of ideas. Exercise and other behavioural interventions might be useful, and a growing number of drugs are being developed that might work for secondary prevention. But we need to do more trials, of more approaches. We need to start them quicker and run them more effectively.

The need for secondary prevention of Alzheimer’s disease is urgent: for all those people now in their 40’s and 50’s, as well as for older people. It’s urgent for the man I live with. If you haven’t guessed already, that man I live with is me. If you want to know who is a candidate for secondary prevention, then look at me. Perhaps look in the mirror too.

Blog kindly republished from the NIHR blog.

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*Professor Sir Simon Lovestone is Professor of Translational Neuroscience in the Department of Psychiatry at the University of Oxford. He is Head of the Informatics and Digital Health research theme at the NIHR Oxford Health Biomedical Research Centre and is an Emeritus NIHR Senior Investigator. He was previously Director of the NIHR Dementia Translational Research Collaboration.

**NIHR is running a campaign to mark World Alzheimer’s Month. Find out more on the NIHR website.

The views and opinions expressed in this blog are those of the authors and do not necessarily reflect those of the NIHR, NHS or the Department of Health.