Dementia What is it? How common is it? What is science doing about it?

Transcription

1 Dementia What is it? How common is it? What is science doing about it? Martin Stevens June 2014 Halesworth U3A

2 Defining dementia. The term dementia describes a set of symptoms including memory loss, mood changes, and problems with communicating and reasoning. Dementia is not part of growing old. It is caused by diseases of the brain, the most common being Alzheimer's.

3 Mild cognitive impairment (MCI) Mild cognitive impairment(mci) is a term used to describe a condition involving problems withcognitivefunction (their mental abilities such as thinking, knowing and remembering). People with MCI often have difficulties with day-to-day memory, but such problems are not bad enough to be defined as dementia.

4 What is dementia? It is an umbrella term that describes about 100 diseases in which brain cells die on a huge scale All damage memory, language, mental agility, understanding and judgement Alzheimer's disease is the most common form, affecting 62% of those living with dementia It gets worse with time and eventually people are left completely dependent on carers It is incurable

5 The size of the challenge UK total: 800,000 Two thirds of people with dementia are women One in three people over 65 will develop dementia

6 Incidence by age Dementia is most common in older people but younger people (under 65) can get it too years: in 1, years: 1 in years: 1 in years: 1 in years 1in 3

7 Future projections UK The number of people in the UK with dementia will double in the next 40 years. 800,000 people with dementia in ,000,000 people with dementia in ,700,000 people with dementia in 2051

8 Worldwide projections Globally, 36 million people have dementia the World Health Organisation predicts numbers will nearly double every 2 decades ie 66 million people will have dementia in 2030 and more than 115 million in In simple terms, that means someone in the world is diagnosed with dementia every 4 seconds. The cost to healthcare is huge, with dementia now one of the greatest pressures on healthcare systems around the world. It costs an incredible estimated 370 billion about 1% of the world sgdp.

9 The causes / types of dementia Alzheimer s disease(62%): A physical disease caused by changes in the structure of the brain and a shortage of important chemicals that help with transmission of messages.

10 So there really was a Dr Alzheimer It is named after the German scientist AloisAlzheimer who identified the condition over a century ago. Alzheimer had studied a patient at the Frankfurt Asylum called AugusteDeter. He first saw her in 1901 and followed her case until her death in She displayed short-term memory loss and disorientation and, after her death, an examination of her brain showed she had the tell-tale protein deposits of amyloidplaques and tau tangles which characterise Alzheimer's disease.

11 The causes / types of dementia Vascular dementia(17%): Caused by problems in the supply of blood to the brain, commonly cause by a stroke or a series of small strokes.

12 The causes / types of dementia Mixed dementia (10%): A type of dementia where a person has a diagnosis of both Alzheimer s disease and vascular dementia. Increasingly seems to be diagnosed in the very elderly. Dementia with Lewybodies(4%): One of the less common forms of dementia. Leading to symptoms similar to Alzheimer s disease and Parkinson s disease. LewyBody dementia occurs when small structures develop in nerve cells, causing the degeneration of brain tissue.

13 Even rarer causes of dementia (3%): Rarer causes of dementia(3%): There are many rarer causes diseases and syndromes that can lead to dementia or dememtia-like symptoms, including Corticobasal degeneration and Creutzfeldt-Jakob disease. Fronto-temporal dementia(2%): rare when all ages are taken into account but relatively common in people under 65, it is a physical disease that affects the brain.

14 Recognising the signs and symptoms of dementia Only 43% of people with dementia receive a diagnosis. Dementia affects everyone in different ways, but you should seek help from your GP if you memory is not as good as it used to be and especially if you notice the following signs and symptoms. Struggling to remember recent events but easily recalling things from the past Finding it hard to follow conversations or programmes on TV Forgetting the names of friends or everyday objects Repeating yourself or losing the thread of what you are saying Problems with thinking and reasoning Feeling anxious, depressed or angry about forgetfulness Other people starting to comment on your forgetfulness

15 Neuropsychological testing: There are a variety of tools to assess memory, problemsolving, attention, vision-motor coordination and abstract thinking, such as performing simple calculations in your head to better characterize the types of cognitive symptoms present, which might provide clues to the underlying cause. The most commonly used test is called a mini-mental state exam, or MMSE. During the MMSE, patients are asked a number of questions which test a variety of common mental skills. Some examples of questions on the MMSE will ask about the date or the person s location and also ask the person to count backward or copy a drawn figure.

16 MMSE: Mini Mental State Examination your not just testing memory!!! Explain to the patient that you would like to ask them some questions about their memory. Some of the question will be quite easy but they might struggle with others. Orientation to time What day of the week is it? What is the date today? Month of the year? What is the season? Year? Orientation to place Can you tell me the name of the country? What is the name of the city/town? What is the name of the county/what shire is this? What is the name of this building? What floor are we on? Memory (registration) I am going to name three things. Once I have finished saying them I would like you to repeat them. Also try to remember them, as I will ask you to repeat them in a little while. Table, Penny and Ball

17 MMSE 2 Attention and concentration Can you spell the word WORLD for me? Please spell it backwards now. Alternatively ask the patient to name the months of the year backwards starting with December. Serial sevens is another option Memory (recall) What were the three things I asked you to keep in mind? Expressive language (naming) Show pen and ask what is this called? Show wristwatch and ask what is this? Expressive language (repetition) Can you to repeat the phrase no ifs, ands or buts

18 MMSE 3 Language Can you do what this says? CLOSE YOUR EYES Please take this paper in your right hand, fold it with both of your hands and put it down on the floor. (Don t hold the paper close to patient s right hand. It should be in the middle.) copying Could you copy this design for me? (it is 2 overlapping pentagons) writing Write a complete sentence-any thing that comes to your mind. (It should have a verb and a subject) MMSE scores Normal range: Mild impairment: Moderate: Severe: 9-0 P.S. you cant work your score own out without the weighted separate score sheet

19 Diagnostic research Brain-imaging scan:mriandctscans look at the structure of the brain and are used to rule out brain tumours or blood clots in the brain as the reason for symptoms. PETscans can look at how certain parts of the brain are working or how active they are. Many scientists are trying to determine if other brain-imaging techniques might be able to identify telltale signs of early Alzheimer's reliably enough to be used as diagnostic tools. Until recently dead peoples brains were all we had to look at. BUT-----

20 Brain scan new in 2014 A dementia brain scan has been introduced for some NHS patients with complicated symptoms. It could help rule out Alzheimer's disease, the most common form of dementia, by hunting for damaged proteins in the brain. A radioactive marker which binds to amyloid, a hallmark of Alzheimer's disease, will be injected. If there is amyloidin the brain then the tracer will show up on brain scans. The test is initially being offered at Imperial College Healthcare London and will be rolled out to other specialist centres.

21 Political/international perspectives G8 dementia: PM calls for UK to lead world in research DC Said --- that scientific breakthroughs hold the key to slowing down or even preventing the onset of the illness and he wants the growing UK life sciences sector to lead the way. more private sector investment eg: GlaxoSmithKline (GSK) 200 million of investments, which will create a centre of excellence in pharma manufacturing technology UK government to double funding research into dementia: committed to spend 52 million in 2012 to 2013 and up to 66 million by 2015 Medical Research Council (MRC) will invest 150 million for clinical research in the UK, with 50 million to better understand how dementia affects the brain, improve early detection and improve treatments to delay progression of the disease. DC said, dementia has emerged as the key health challenge of this generation and a global response will be required.

22 G8 Dementia Summit outcome 2 (2014) The G8 countries agreed to a package of measures that will see collaboration on research, sharing of expertise and closer cooperation as part of a worldwide push similar to global efforts to fight cancer, malaria and HIV and AIDS.

23 So why no cure? 1 Why haven't we found a cure? Scientists still don't fully understand it. Appears to result from a complex interaction of genes, lifestyle factors and other environmental influences. Without knowing the exact mechanisms that cause damage, especially in Alzheimer's, it's impossible to target the disease process effectively. The blood-brain barrier problem. It keeps the brain healthy by preventing toxins reaching the brain. But it can also stop treatments getting through or working effectively. Drugs may only partly cross the barrier as they are too large or awkwardly shaped, which means that dangerous doses would be needed for them to work. Even if drugs were found that could target the proteins causing damage to brain cells in neurodegenerative disease, the damage may already have been done.

24 Why No Cure 2 Finally, dementia is very difficult to diagnose. There is no single test to pinpoint the disease. There is also a stigma attached to the condition, as well as fear, that can make some health professionals reluctant to give the diagnosis. Some experts argue that with no effective treatments, early diagnosis has no benefits. Estimated that of those living with dementia in the UK only half will have received a formal diagnosis. This causes problems for drug trials, as scientists can only guess what type of dementia patients have, and can only confirm their diagnosis at post-mortem.

25 Types of research Scientific research about Alzheimer's can be broadly categorized into five general areas: 1. Research about possible causes, which includes the identification of risk factors clarification of the underlying associated biological processes. 2. Research aimed at improving early diagnosis, including the identification of cognitive and biological "markers" ( tell-tale signs) for the disease and the use of brain imaging (scans)to identify brain changes even before symptoms are present; 3. Research to develop new treatments, including medications that target the underlying biological changes (or pathology) in the brain, and non pharmacological approaches to managing behavioural symptoms; 4. Research focused on prevention, which includes understanding whether certain drugs or lifestyle factors may exert a protective effect. 5. Research about care and management - what types of education are most effective and what types of support are most useful.

26 Bad Science?? Study suggests link between cynicism and dementia 1. People who have a cynical distrust of others, and think their motives are selfish, could have a higher risk of developing dementia, a study has said. 2. Researchers compared levels of cynical distrust in 622 people with the incidence of dementia. 3. They said people with high levels of distrust were twice as likely to develop dementia. 4. Experts said any findings that helped understand the disease were important, but called for larger studies. 5. In 1998, volunteers, with an average age of 71, were asked to rate their agreement with statements such as "I think people would lie to get ahead", or "it is safer to trust nobody", said the researchers. 6. Scientists at the University of Eastern Finland said 46 people had developed dementia in the following decade. 7. Fourteen of the 164 people who showed high levels of cynical distrust in 1998 had developed dementia in this time, compared with nine out of the 212 people with low levels. 8. She said: "These results add to the evidence that people's view on life and personality may have an impact on their health.

27 Bad Science? 2 1. "People with different personality traits may be more or less likely to engage in activities that are beneficial for cognition, such as healthy diet, cognitive or social activities, or exercise. 2. "Or personality may act via morphological changes or structural differences in brains. Also, inflammation has been suggested as one link between cynicism and worse health outcomes." 3. She said the study was controlled for socioeconomic factors, age, sex, health status, and lifestyle, such as smoking and alcohol use. 4. She added it was "really important" to replicate the findings on a much larger scale, to prove the link. 5. Dr Simon Ridley, head of research at Alzheimer's Research UK, said: "With the rising numbers of people affected with dementia, any addition our understanding of what might affect disease development is important." 6. He said that as only a small number of people in the study developed dementia, he would want to see a larger study conducted to be "more confident" in the proposed link. 7. Dr Ridley said the volunteers with a high level of cynical distrust could have been already beginning to develop dementia, and that depression, which may be both a risk factor and a symptom for dementia, could account for the cynicism. 8. "The biggest risk factor for dementia is age, by far," he said.

28 Medication Drugs used to treat people with Alzheimer's/Dementia fall into two broad categories 1. drugs to treat cognitive symptoms, such as memory problems and other mental deficits of Alzheimer's, -i.e. slow it down 2. drugs to treat behavioural symptoms that do not respond to non-pharmacological behaviouralmanagement approaches. Often categorized as anti-agitation drugs. I.e. To manage symptoms

29 Where are the new drugs to stop Dementia? Only about 10 % spent on Dementia drug research development by Pharma compared with Cancer. Only 3 new not very effective drugs in past 20 years - many more for cancer. Do Pharma need different incentives to develop / market - political consensus/ will seems to be moving in this direction. G8 and UK govt now making more positive noises about supporting research. Perhaps this is why much of the research you can find published is on diagnosis, prevention and using existing products( eg vitamins /superfoods ) Pharma do not seem to share their negative trials so there may be much wasted duplication of effort.

30 Nature or Nurture? Genetic 1 Scientists who study the genetics of Alzheimer's distinguish between familial Alzheimer s disease, which runs in families, and sporadic Alzheimer's disease, where no obvious inheritance pattern is seen. True familial Alzheimer s disease accounts for less than 5% of Alzheimer s cases. Sporadic Alzheimer s is much more common. Familial Alzheimer s Disease All Familial Alzheimer s disease known so far has an early onset, and as many as 50 percent of the cases are now known to be caused by defects in three genes located on three different chromosomes. Even if one of these mutations is present in only one of the two copies of a gene inherited from a person's parents, the person will inevitably develop that form of early-onset Alzheimer s. However, the total known number of these cases is small (between 100 and 200 worldwide), and there is as yet no evidence that any of these mutations play a major role in the more common, sporadic or non-familial form of late-onset Alzheimer's.

31 Genetic 2 Sporadic Alzheimer s Disease Although there is no evidence that inheritance of mutated genes causes late-onset Alzheimer's, genetics does appear to play a role in the development of this more common form of the disease. Research has found an increased risk for late-onset Alzheimer's in people who inherit one or two copies of a particular variation of a gene called apolipoprotein E (APOE) -- the variation known as APOE e4 The finding that increased risk is linked with inheritance of the APOE e4 allele has helped explain some of the variations in age of onset of Alzheimer's disease based on whether people have inherited zero, one, or two copies of the APOE e4 allele from their parents. The more APOE e4 alleles one inherits, the lower the age of disease onset. The relatively rare APOE e2 allele may protect some people against the disease: It seems to be associated with a lower risk for Alzheimer's and a later age of onset if the disease does develop. APOE e3 is the most common version found in the general population and may play a neutral role in Alzheimer's risk.

32 Non-Genetic Risk Factors Age During the course of normal aging, the brain undergoes a number of changes: Some neurons (nerve cells) in certain brain regions die, although most neurons important to learning are spared; Some neurons and the fibres that connect them to other neurons shrink and degenerate, especially neurons in areas of the brain important to learning, memory, planning and other complex mental activities; Tangles develop within neurons and protein plaques develop in the areas surrounding neurons; Tiny structures inside neurons that metabolize energy for cell functions (mitochondria) become more susceptible to damage; Inflammation (swelling) increases, which can injure nerve cells, such as after a head injury; In healthy older people, the impact of these changes may be modest, resulting in various degrees of age-related memory decline. In people who have Alzheimer's, however, some of these changes are much more extreme, with devastating consequences. Determining how the brain changes in normal aging and what relevance this has to Alzheimer's is an important area of research.

33 Non genetic 2 Education level Research suggests that the more years of formal education one has, the less likely one is to develop Alzheimer's. Some experts theorize that longer education may produce a denser network of synapses, the nerve-fiber connections that enable neurons to communicate with one another. This may create a kind of "neural reserve" that enables people to compensate longer for the early brain changes associated with Alzheimer's. Race and Ethnicity African-Americans and Hispanics are at a higher risk for developing Alzheimer s. Studies show that African-Americans and Hispanics were almost twice as likely to develop Alzheimer s as white Americans of the same age. The reasons for this are unclear, some speculation that it may be that these groups have a higher incidence of high blood pressure and diabetes, which are known to increase one s chances of developing Alzheimer s. High blood pressure and high cholesterol Growing evidence that many of the well-established risk factors for cardiovascular disease, including high cholesterol and high blood pressure, may also be risk factors for Alzheimer's disease. Studies are showing that what's good for the heart - keeping cholesterol and blood pressure in check - may also be good for the brain. Diabetes Diabetes is implicated as a risk factor for eventually developing Alzheimer's disease. Ongoing studies are attempting to understand the connection. Some diabetes drugs appear to slow the cognitive decline associated with Alzheimer's disease.

34 Non Genetic 3 Head trauma Alzheimer's occurs more often in people who have suffered traumatic brain injury earlier in life. Ongoing research is pursuing this link. A history of head injury is clearly a risk factor for Alzheimer's in people who carry the APOE-4 Alzheimer's gene. Aluminium One of the most publicized and controversial hypotheses about risk factors for Alzheimer's concerns aluminium. Many studies have either not been able to confirm this or have had questionable results. Studies have found that groups of people exposed to high levels of aluminium do not have an increased risk. Scientists can say only that it is still uncertain whether exposure to aluminium plays a role in Alzheimer's disease. Dietary factors The evidence that what you eat matters to your brain is growing fast. Many studies have recently reported that many of the same factors that contribute to poor heart health also increase one s risk of cognitive decline or developing Alzheimer's disease. Taken as a whole, studies support the notion that eating a balanced diet and eating in moderation throughout your life is just as important to long-term cognitive health as it is to heart health. FINALLY Gender Alzheimer s is more prevalent among women, but this is more likely because women, on average, tend to live longer than men and not because gender is a risk factor for Alzheimer s.

35 Midlife Stress May Increase Dementia Risk Sweden study pub 2014 Women who experience a lot of stress in middle age are at increased risk of developing Alzheimer s disease and other forms of dementia late in life, according to a new report. The findings come from a study of 800 women living in Sweden who were followed for nearly four decades. Though the study did not look at men, the results suggest that stress may have longstanding detrimental effects on the brain for all of us. Researchers examined the long-term medical and cognitive health of 800 women in Gothenburg, Sweden. The women started the study in 1968, when most were in their 40s or 50s. Over the next 38 years, the women were given regular health assessments every 5 to 10 years, including looking for signs of the memory loss of Alzheimer s and other types of dementia. At the beginning, the women were asked whether they had experienced major stresses like divorce, death of a spouse or child, or serious illness in a close family member. Other sources of stress they were asked about included unemployment, either themselves or a spouse, lack of social support, or a history of abuse.

36 Sweden and Stress 2 At each follow-up visit, the women were also asked whether they had experienced symptoms of stress lasting at least a month. The more stressful events they had experienced in the past, the more likely they were to experience symptoms of distress. Initially, about 25 percent of the women had experienced one major life stressful event, 23 percent had experienced at least two, 20 percent had experienced at least three, and 16 percent had experienced four or more. The most common major stressor was mental illness in a close family member. During the follow-up period, over the next four decades, around one in five of the women had developed dementia, most often Alzheimer s, at an average age of 78. Those who reported experiencing the most stressful events in middle age were at 21 percent increased risk of developing Alzheimer s in old age, and at 15 percent higher risk of developing other forms of dementia. Researchers note that stress can affect the central nervous system and immune system, and that levels of stress hormones may remain high for many years after a traumatic event. Other studies have shown that stress can damage brain cells and promote inflammation, which has been increasingly linked to Alzheimer s disease. Stress has also been linked to high blood pressure, which can also be bad for the brain. As we already know many factors can contribute to Alzheimer s, including age and genetics. Long-term stress may be one more factor that may play a role in the onset of dementia.

37 University of Oxford, the Oxford Radcliffe Hospitals NHS Trust and the University of Oslo in Norway. Vitamin B link? The study received funding from a number of sources, including the Charles WolfsonCharitable Trust, the Medical Research Council, the Alzheimer s Research Trust. Pub Brain shrinkage is not the same as dementia doses of vitamin B can halve the rate of brain shrinkage, a process that can precede Alzheimer s disease and dementia. Well-conducted two-year trial, which compared vitamin B pills with inactive placebo pills in 271 elderly people with mild memory problems. Study found that those given vitamin B experienced brain shrinkage (atrophy) 30% slower than those given inactive tablets. However, slower brain shrinkage may not necessarily lead to any improvement in symptoms. This research does not show that vitamin B can prevent Alzheimer s disease or dementia because there is no evidence to confirm that slower brain shrinkage will lead to benefits for people with early dementia symptoms. Nevertheless, these results are promising and clearly warrant more research. So -- Should we take vitamin B supplements? This was early research and cannot yet tell us whether vitamin B can slow the progress of dementia. However, this research only assessed an outcome of brain shrinkage, which is not necessarily the same thing. The functional effects of reducing brain shrinkage were not investigated and it is an extrapolation to conclude that B vitamins improved cognitive health or protected against Alzheimer s disease.

38 Vitamin B link Conclusions - an important but early study in establishing the effects of vitamin B on the stages of brain atrophy that precede Alzheimer s disease. - assessed the effects of the vitamin on the rate of brain shrinkage, a process that has been linked to old age, mild cognitive impairment and Alzheimer s disease. Although other studies have found that the rate of brain atrophy is linked to cognitive decline, this particular study did not assess whether the participants brain changes translated into changes of cognitive ability or memory. A well-conducted, albeit small, study. It was a randomised controlled trial, which is the most appropriate way to assess the effects of a new treatment. Researchers highlighted some shortcomings: ie -- The treatment was a combination of three B vitamins, so the researchers could not determine whether these have different effects individually. The study was not set up to assess the effects of treatment on cognition, but only on the rate of change in brain measurements. Based on the evidence gathered so far, it is too early to claim that vitamin B can prevent clinical disease, but these results are promising. More research will undoubtedly follow

39 Demographics -a recent challenge to the orthodoxy Very recent studies (Lancet) suggest Dementia rates are not increasing as fast as life expectancy. Studies 20 years ago predicted 900K in UK by now but only 650K is current estimate Seems people are developing Dementia later in life. Dutch study also found people were stronger and smarter for longer than in previous studies. One theory is that as populations become more educated dementia as well as death is delayed. The idea of an increased cognitive reserve has developed the smarter we get the bigger it gets.

40 Building up your cognitive reserve - Has the U3Aa role here? Less controversial than brain training it is argued that cognitive reserve may be increased by Taking up taxing hobbies Playing cards such as Bridge Playing a musical instrument Having a full social life Just existing/ engaging in the in modern connected, hi tech and stimulating world. Numerous observational studies indicate a dementia preventative link connected to these

41 Future - is it all bad? Researching this talk has made me less pessimistic. Prevention studies seem to offer some ability to take some elements of personnel control - the demographics are not so bleak as they were. Politicians worldwide, academia and big pharma seem at last to be taking this issue more seriously. This will likely bring forward progress in preventing, delaying and stalling many types of dementia.