Understanding Dementia - Q3 - Sep 2018

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Understanding Dementia

How early detection of dementia is key to helping find future treatments P6

How our understanding of dementia has changed with research in the past 50 years CREDITS: DR LIZZIE GLENNON, KINGS COLLEGE LONDON VIA ALZHEIMER’S RESEARCH UK

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IN THIS ISSUE How research into care can help improve quality of life of those living with dementia

How World Alzheimer’s Month is helping us to understand the scale and complexity of the dementia crisis

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READ MORE ON HEALTHAWARENESS.CO.UK How communities and businesses can become more dementia friendly

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Dementia isn’t ‘a normal part of ageing’

Hilary Evans Chief Executive, Alzheimer’s Research UK

This World Alzheimer’s Day, over half a million people in the UK are living with the disease, but with continued support, research can transform lives.

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ast year, Alzheimer’s and other forms of dementia emerged as the UK’s leading cause of death.

With no treatments to stop or cure them, these are diseases that sadly, no one has yet survived.

We firmly believe that research can and will change that. In recent years we’ve welcomed greater efforts from government, industry and charity to prioritise the condition.

But our recent polling shows that one in five UK adults still believe dementia is a normal part of ageing and there remains a common belief that nothing can be done to change the outlook for Follow us

those affected. We must continue to shine a spotlight on Alzheimer’s and other dementias, to provide hope and empowerment through research for those affected today, and to deliver advances for people affected by dementia in future.

Today, Alzheimer’s Research UK has launched our Make Breakthroughs Possible campaign as a rallying cry for change. A call for everyone to take action and bring forward the day when Alzheimer’s and other dementias no longer cast a shadow over so many lives. The UK must remain a leading location for breakthrough dementia research.

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Research has already helped millions of people recover from cancer, overcome heart disease, and lead long and healthy lives in the face of HIV. We can make the same progress for people with dementia too. But medical breakthroughs don’t just happen by themselves. People are making them possible.

It’s not just scientists who have a role to play. Government must ensure the UK remains a leading location for cutting-edge science and the pharmaceutical industry must continue to invest in this important area of research. We also need people with and without

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dementia to take part in pioneering research studies, including vital clinical trials.

Help research by taking part in a clinical trial Clinical trials are key for bringing about the treatments that will transform people’s lives and these studies would be impossible without the volunteers who put themselves forward for this type of research.

Dementia is now our greatest medical challenge but by supporting research, we can all help to make breakthroughs possible.

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Alzheimer’s research: it’s not all doom and gloom

Professor Claude Wischik Co-Founder and Executive Chairman, TauRx Pharmaceuticals

Following more than a decade of no real progress in finding effective treatments, the need for continued research into Alzheimer’s disease is more critical than ever.

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lthough treatments are available to reduce Alzheimer’s disease (AD) symptoms, no disease-modifying drug able to halt or reverse cognitive decline has been found.

In recent years, the disappointing results of several clinical trials in AD have dominated the news making some in the pharmaceutical industry question their involvement in research of this condition. However, the need for ongoing clinical research

into AD is more important than ever.

An estimated 47 million people are living with AD. This figure is predicted to reach epidemic proportions in the next 30 years and threatens to have a major socio-economic impact on people, caregivers and public healthcare systems worldwide.

Targeting novel Alzheimer’s pathways So far, most research has focused on amyloid-based treatments in late-stage AD but none of these have completed clinical development.

Fortunately, other therapies are being investigated with a focus on the earlier stages of AD, where degeneration of the neurons in the brain could be halted or even reversed.

The Tau tangle pathway is an increasingly interesting avenue to pursue. Tau tangles typically appear years before AD symptoms are apparent, which is why TauRx has focused its research in this area for nearly 30 years.

New Phase III dementia research TauRx has started recruitment into its latest clinical trial, LUCIDITY. People with early symptoms of AD will be studied to confirm the potential of TauRx’s treatment and assess whether it can delay progression of disease pathology in patients with early AD. In previous trials, this treatment has demonstrated potentially beneficial results, and so we believe it is important to pursue this avenue of

research to find lasting solutions for patients and their families.

Continued clinical research and collaboration into novel AD therapies is more important than ever. Together, we can go further and faster to provide major advances to patients, carers and healthcare systems, and to offer hope in this devastating disease.

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Advancing Clinical Research in Dementia At IXICO, our mission is to transform the treatment pipeline for neurodegenerative diseases through the application of advanced medical imaging and digital health technologies.

The ability to measure the progression of neurodegenerative disorders through imaging and other biomarkers is key to understanding dementia, helping to drive development of new treatments. IXICO’s specialist data analytics are powering some of the most important clinical trials in neuroscience today, supporting better study design, WH[PLU[ ZLSLJ[PVU HUK HZZLZZTLU[ VM KY\N ZHML[` HUK Lɉ JHJ` for better outcomes.

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Care is as vital as a cure Dementia is the biggest health and social care challenge we face.

In the UK, someone develops dementia every three minutes and while one million people will be living with dementia by 2021, dementia research still trails far behind other health conditions, after decades of underfunding.

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s there’s currently no cure for dementia, it’s vital that people living with dementia receive good quality care

that empowers them to live well and helps them to do the things they enjoy. Yet less than 5% of all dementia research, globally, addresses the care and support that people with dementia rely on every day. Today we have a major opportunity to harness the potential of technology to transform our understanding of dementia and how to manage it.

Local health and social care services are facing many complex issues with limited resources. To

Jeremy Hughes Chief Executive, Alzheimer’s Society

offer the highest standard of care, in a cost-effective way, commissioners depend on research and evidence-based practice. Alzheimer’s Society funded Centres of Excellence are making in-roads to build evidence, the UK Dementia Research Institute (DRI) offers new opportunities, but we urgently need to see further investment.

Alzheimer’s Society is leading the way in rebalancing investment between biomedical and care research. We have invested £5.6

million in three care research Centres of Excellence across the UK, and as a founding funder of the UK Dementia Research Institute (DRI), are supporting the investment of £20m for a care and technology work stream.

Until the day we beat dementia we are committed to researching ways to make quality of life better for people living with living with the condition in the UK and their carers too.

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Why is dementia so sexist?

Dementia is sexist. This devastating condition disproportionately affects more women than men, with women with dementia Dr Aoife Kiely Research Officer, outnumbering men two to one.

Alzheimer’s Society

Women are, statistically, more likely to live longer than men and, unfortunately, the risk of dementia increases with age. But dementia is caused by diseases of the brain, not age alone, so what is it that makes women more vulnerable to dementia?

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he truth is we don’t fully know.

One of the main theories rests with the female hormone, oestrogen. Oestrogen affects the development of the brain and, at the recent AAIC conference, was linked to women having better verbal memory than men at all ages (even in people with mild cognitive impairment). Women’s better verbal memory may be masking early symptoms of dementia,

leading to under-diagnosis and lost opportunities for early intervention.

Also, during the menopause, women stop producing as much oestrogen, which results in a loss of the hormone’s influence on blood pressure and cognition. This may explain why hypertension has been shown to be more likely to increase a woman’s risk of dementia than a man’s, despite hypertension being more common in men of

the same age.

Our researchers are on the case, investigating the role of blood pressure in dementia and striving to improve all aspects of diagnosis, care and potential treatment. But we need more funding to continue this work.

There hasn’t been a new drug for dementia in 15 years, so it’s important to keep research at the forefront of the agenda and make sure that upcoming treatments work for everyone.

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Lack of awareness remains the biggest issue facing the global dementia community

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Early diagnosis is key for tackling Alzheimer’s Could successful dementia treatment be a matter of timing?

Dr Carol Routledge Director of Research, Alzheimer’s Research UK

Paola Barbarino Chief Executive Officer, Alzheimer’s Disease International Lack of awareness remains the biggest issue facing the global dementia community. The WHO’s Global Plan was a watershed moment in dementia advocacy, but watershed events must be followed by longer term change.

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0 million people now live with dementia globally. That’s one person every 3 seconds, and this number is expected to triple by 2050.

Up to 90% of people living with dementia do not receive a diagnosis, and many cannot access support. Some countries do not have a name for Alzheimer’s disease or other dementias, especially in low and middle-income countries. These ongoing and increasing issues go to the core of this year’s World Alzheimer’s Month campaign, called: Every three seconds.

This is why the focus of this World Alzheimer’s Month is on the personal stories of those affected by dementia.

50 million people now live with dementia globally.

Our actions for World Alzheimer’s Day 2018:

On World Alzheimer’s Day, Alzheimer’s Disease International will release our 2018 World Alzheimer Report, The State of the Art of Dementia Research: New frontiers.

This report adopts a more accessible journalistic style, expanding the research discussion to a wider audience. It asks why there has been so little in terms of treatments over the last 20 years, explores hopes and aspirations, and asks the key question: “when will there be a breakthrough?”

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Researchers around the world are working to improve the detection of diseases like Alzheimer’s and make earlier diagnosis possible.

But why are we focusing valuable research efforts on improving the diagnosis of diseases that we can’t yet effectively treat?

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ell firstly, when families notice that a loved one is starting to behave differently, they generally want to know why as quickly as possible. Receiving a dementia diagnosis often changes people’s priorities and bringing that day forward gives people more time to take stock and plan for the future.

Secondly, it gives people more opportunities to adopt a lifestyle that could help slow disease progression.

And thirdly, while current treatments for diseases like Alzheimer’s are limited, they are thought to have the most impact in the early stages.

It’s true for most diseases – the sooner you can tackle them, the better the chance of treating them successfully.

Early detection is a major focus for health services around the world, with screening programmes for diseases like heart disease and bowel cancer helping to shift the detection of these diseases earlier, when treatment is more likely to be successful.

Symptoms can occur 20 years before the disease affects people’s lives

By the time someone starts to show symptoms, a disease like Alzheimer’s has already caused significant damage to their brain. Research has revealed that disease processes get underway in the brain up to 20 years before symptoms start to affect people’s lives.

This presents a window of opportunity, during which we could detect the disease and start treatment.

At the moment, we can only trial potential Alzheimer’s medications after this pre-symptomatic window.

This may be a bit like trying to tackle a late-stage cancer and it is likely to be part of the reason why experimental Alzheimer’s drugs, which show promising signs of being able to tackle key disease-processes, haven’t yet been successful in clinical trials.

Many researchers now believe that we may have already developed effective Alzheimer’s treatments that can slow the progression of the disease.

But because we can’t diagnose people early enough, they are languishing in a lab instead of changing people’s lives.

We want to detect Alzheimer’s at least 10 years earlier

Alzheimer’s Research UK is proposing a global solution to transform the diagnosis of the diseases that underlie dementia. We want to detect diseases like Alzheimer’s 10-15 years earlier than we do now so that, in turn, we would be able to treat those affected one or even two decades earlier.

The last few years have seen a transformation in how digital technology is used to collect and analyse patient data. We are working to unite key players in data science and machine learning with leading dementia scientists and clinical experts, to lead a digital dementia revolution that will track the very earliest stages of diseases like Alzheimer’s.

We want to use this knowledge to help ensure an accurate diagnosis for everyone at a time that’s right for them, giving future treatments the head start they need to have the biggest impact on lives.

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Next-Generation Sequencing: How technology is accelerating Alzheimer’s disease research

IMAGE: THERMO FISHER

Karen Jones Regional Market Development Senior Manager, EMEA Sequencing, Thermo Fisher Scientific

Researching a complex disease like Alzheimer’s is not a simple undertaking.

However work being done in laboratories equipped with revolutionary technology may have a major impact on how Alzheimer’s disease is diagnosed and how it may be treated in the future.

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iomarkers, either chemical or genetic, are the cornerstone of research to better understand Alzheimer’s disease.

The presence of particular biomarkers known to be associated with the disease can potentially serve as risk indicators or confirm early onset for patients who are presenting symptoms. But much more research needs to be done to elucidate the root cause of the disease so that more effective therapies can be developed in the future.

“Our customers play a key role in investigating the genetic causes of this disease,” says Karen Jones, Regional Market Development Senior Manager, EMEA Sequencing, Thermo Fisher Scientific. “We help support their important work by serving as their technology partner. Our sequencing solutions are designed to help them better understand the genetic pathways involved for the future development of new treatments.”

Achieving Efficiency with Gene Panels

Genetic research sometimes involves whole exome and whole genome sequencing to find those

predisposing biomarkers, which might be single-point mutations or small DNA changes. However the time-consuming process of analyzing the approximate 19,000 protein-coding genes, which represent less than 1.5% of the human genome is taxing on resources. Expanding the search for disease-causing genetic mutations to the entire genome, including sequences for which no known function has been determined, is an even greater informatics challenge.

Targeted next-generation sequencing (NGS) technology developed by Thermo Fisher Scientific helps overcome these hurdles.

It’s a way of cutting through the complexity of the human genome to quickly identify genetic factors By leveraging gene panels, which contain all the known biomarkers associated with Alzheimer’s disease, researchers are able to very quickly analyze samples and identify these mutations.

With a single sequencing run lasting less than 24 hours, for example, researchers are able to screen multiple familial samples across the most likely genes, and determine whether the culprit genes have been inherited.

If causative links are found, scientists then use a range of approaches to understand how these gene variants influence

disease processes.

This targeted NGS approach is highly efficient and leverages the most up to date discoveries that have been made in this field of disease research. It enables scientists to better understand why and how the gene variants are involved in the disease process.

Should scientists wish to expand their search beyond known genes, microarray technology allows researchers to spot a lot of areas of the human genome on a chip and see whether those are coming up in the samples, and this technology can deliver easy to interpret answers within a few days. Essentially, researchers look for known mutations that have already been identified as potentially causative and see whether they come up.

This approach can be used for both genetic variant discovery and gene expression changes.

‘It’s a way of cutting through the complexity of the human genome to quickly identify genetic factors that correlate with disease onset and progression”, explains Karen. These discoveries lead to the next phase of research which is to develop routine tests that can be used to predict disease predisposition and prognosis as well as to identify future targets for therapy development. Linking together the research element to routine tests is an area known as translational research; a field which is rapidly expanding, thanks to next generation sequencing approaches like these.

Genetics vs Lifestyle

While Alzheimer’s might be hereditary, it is also a disease that

is affected by lifestyle factors.

Correlating genetic learnings with lifestyle factors offers scientists a way to identify lifestyle changes that can be made to alter disease outcomes.

This multifaceted approach is shaping the way that research is developing.

Research is continually moving forward in this space. Blood-based NGS tests are among the latest approaches coming online as potential tools that may one day make their way into routine clinical care. Dr Lesley Cheng, is a post-doctoral scholar at La Trobe University in Melbourne, Australia who works on the development of a novel blood test for detecting Alzheimer’s disease as soon as amyloid plaques first appear in the brain. Her technique involves the identification of microRNA biomarkers within circulating exosomes in our blood, again using Thermo Fisher’s next generation sequencing technology. She is turning these discoveries into fast and costeffective tests using Applied BiosystemsTM TaqMan® assays.

Francesca Baker

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Top 5 facts Business benefits of IMAGE: GETTYIMAGES

on dementia in the UK

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There are 850,000 people with dementia in the UK, with numbers set to rise to 1 million by 2021

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225,000 will develop dementia this year, that’s one every three minutes

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1 in 6 people over the age of 80 have dementia

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There are over 40,000 people under 65 with dementia in the UK

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Two thirds of people with dementia live in the community, a third live in care homes SOURSE: ALZHEIMER’S SOCIETY

becoming dementiafriendly There are now 850,000 people living with dementia in the UK and someone develops it every three minutes.

It will affect everyone, in every sector and every industry, from customers to staff.

Emma Bould Programme Partnership Project Manager,

Alzheimer’s Society

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ith the UK statutory retirement age rising, we will see many more people developing dementia while still in employment and others seeking to combine being a carer with working. Equally, consumers want businesses and organisations who value their customers, and who are aware of their needs. Businesses must future proof against dementia but this will only be achieved with greater awareness, understanding and support for customers and staff who are impacted by dementia.

Supporting people with dementia People with dementia have the right to live a life they love and to continue doing the things they enjoy. But, too often, people with dementia don’t feel included in their communities and face isolation. Trevor from Middlesex told us about his wife, Yvonne, who worked at a well-known, chain supermarket. Her employer was very supportive when her capabilities declined because of her dementia. The store adapted Yvonne’s tasks, which eased the difficulties she was having and made her feel valued.

But not all organisations may feel they

are able to offer that level of support.

From retail to housing, utilities to entertainment, finance to transport, all sectors have a part to play in supporting people living with dementia to continue to do the everyday things many of us take for granted, such as shopping, banking and hopping on the bus.

Dementia-Friendly Business Guide Alzheimer’s Society has produced a Dementia-Friendly Business Guide, which highlights the many ways a business can better support people affected by dementia. It is often the simplest things that help best. The charity also runs Dementia Friends, the largest social action movement on dementia. It was developed to tackle the lack of understanding people with dementia face on a day-to-day basis and can be rolled out across organisations as a key step to becoming dementia friendly.

Becoming a dementia-friendly organisation isn’t just a socially responsible step – it has clear business benefits, including competitive advantage and enhanced brand reputation.

Why dementia is a global crisis

Jeremy Hughes CEO, Alzheimer’s Society & Chair Global Alzheimer’s and Dementia Action Alliance (GADAA)

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n the three seconds it takes you to read this sentence, another person will have developed dementia worldwide. Dementia is a global health crisis – 50 million live with the condition worldwide and it’s now one of the leading causes of death. We explore why dementia is a global health and development priority that can no longer be ignored.

1. Dementia costs the global economy $1trillion annually That’s a cost greater than the GDP of all but the 15 richest economies in the world. Eighty per cent of these costs account for the unpaid and formal care for people living with dementia, two-thirds of which is delivered by women.

Despite this, many countries are unprepared for financing longterm care. As social changes in low-middle income countries (LMICs) mean less family members are able to provide care, the urgent need for social care will shift to the formal sector. The global cost of dementia will double to US$2trillion by 2030.

Yet diagnosis rates are low, research is underfunded and people are receiving sub-standard or no care, with stigma in many communities remaining rife. In some countries, there’s not even a word for dementia.

2. Dementia is projected to affect 75.6 million by 2030 and almost triple by 2050 to 131.5 million.

Worryingly, ageing populations –

especially in low to middle income countries – are set to exacerbate prevalence rates. The potential ramifications of this are huge.

More than half of people with dementia worldwide (58%) live in LMICs – and the number in some regions is expected to increase fivefold by 2050. The number of people living with dementia in high income countries is also expected to double by 2050. With no new drug to reduce symptoms in 15 years, it has never been more vital to invest in research.

3. An average of three quarters of people with dementia have not received a diagnosis worldwide As few as one in 10 individuals receive a diagnosis for dementia in low and middle income countries,

and less than 50% are diagnosed in high income countries.

Globally there is a persistent lack of understanding that dementia is a medical condition and not a normal part of ageing. People living with dementia all over the world desperately need access to a medical practitioner who can provide a diagnosis and help to plan necessary support.

Without action the world is woefully unprepared for the dementia crisis. This World Alzheimer’s Day, GADAA, led by Alzheimer’s Society, Alzheimer’s Disease InternationaI and others, are urging international civil society to unite in recognising dementia as a core development issue, taking action to beat dementia.

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How fundraising is driving forward research

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Alzheimer’s is a disease, we can beat it through research

UK dementia research charities funded approximately £23m of research in 2015/16 compared to £310m of charity research funding for cancer.1

2. £114.8m – the total put towards dementia research by charities and government 2016/17.2

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The Association of Medical Research Charities (AMRC) reports that charities funded 45% (£1.6bn) of publicly funded medical research nationally in 2016.3

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Between 2010 and 2012, 17% of approved drugs in the EU originated in not for profit organisations (Academic, public or PPPs).4

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Every £1 of UK Public funding for research generated between £1.13 and £1.60 of private investment.5 IMAGE: GETTYIMAGES 1: ALZHEIMER’S RESEARCH UK ANNUAL REVIEW, ALZHEIMER’S SOCIETY ANNUAL REVIEW, ‘HOW WAS RESEARCH FUNDING FROM NCRI PARTNERS SPENT IN 2015?’, NCRI 2: ALZHEIMER’S RESEARCH UK ANNUAL REVIEW, ALZHEIMER’S SOCIETY ANNUAL ACCOUNTS AND PARLIAMENTARY WRITTEN QUESTION NO. 144915 (2018) 3: 2017 INFOGRAPHIC (12TH JUNE 2017) ASSOCIATION OF MEDICAL RESEARCH CHARITIES 4: LINCKER ET AL. (2014) REGULATORY WATCH: WHERE DO NEW MEDICINES ORIGINATE FROM IN THE EU? BY NATURE REVIEWS DRUG DISCOVERY.13, 92–93 [SUMMARY ON EUROPEAN MEDICINES AGENCY WEBSITE] 5: WHAT IS THE RELATIONSHIP BETWEEN PUBLIC AND PRIVATE INVESTMENT IN SCIENCE, RESEARCH AND INNOVATION? (2015) BY ECONOMIC INSIGHT COMMISSIONED BY THE DEPARTMENT OF BUSINESS, INNOVATION AND SKILLS

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Dr David Reynolds Chief Scientific Officer, Alzheimer’s Research UK

This year is the fiftieth anniversary of a crucial milestone in dementia research. In 1968, a team of researchers showed that Alzheimer’s disease was the major cause of dementia.

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efore 1968, Alzheimer’s was considered a rare disease that affected people relatively early in life, and dementia was largely seen as a normal consequence of ageing.

The discovery that Alzheimer’s disease was the major cause of dementia was a huge leap forward in our understanding of dementia, and it set the modern era of research in motion.

But dementia research was late out of the gates. By 1968, pacemakers and coronary bypass surgery were already transforming the lives of people affected by heart disease, and combination chemotherapy was being rolled out for the treatment of cancer. While funding for dementia research still lags behind these other disease areas, the last 50 years have seen incredible scientific progress that is paving the way to better treatments.

Bringing a treatment to market is usually the culmination of decades of research. The process begins when scientists make a discovery about a disease and it continues through multiple stages of biological testing, chemical development, and vital clinical trials.

Research starting in the 70s led to medications by the 90s In the late 90s, the first medications for Alzheimer’s made it into the hands of patients. These treatments have their routes in pioneering research from the 1970’s, which revealed that people with Alzheimer’s have reduced levels of a key brain chemical.

While these drugs have now helped millions of people, they can’t change underlying disease processes or protect the brain from damage. In 2013, the inter-governmental political forum, G8,

set a target of finding the first diseasemodifying dementia treatment by 2025, a date that is now looming large. This is an ambitious goal, but advances in our understanding of Alzheimer’s have brought it within reach.

As genetic research matured into the 1990s, researchers revealed how the hallmark Alzheimer’s protein, amyloid accumulates in the brain. Anti-amyloid drugs are now the front runners in the race for the first treatments that could actually slow or stop the disease, and several of these medications are now making their way through clinical trials.

There is more to dementia than just Alzheimer’s But Alzheimer’s is just one form of dementia and is in itself a complex disease with multiple facets that will need to be tackled in different ways. The first diseasemodifying drug will not be a cure-all, and we need to make sure that it will be the first of many.

From a standing start 50 years ago, research progress has been accelerating alongside hard-won increases for funding.

While dementia research is still playing catch-up, initiatives like the Alzheimer’s Research UK Drug Discovery Alliance are exploring a diverse portfolio of drug targets and are positioned to seize upon new research findings and develop these ideas towards new drugs that can be tested in clinical trials.

Ultimately the progress that matters is more and better ways to help people affected by dementia. While these breakthroughs lie ahead, scientists have been making them possible through decades of research innovation and scientific success.

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