Alzheimer s Disease 1818 Society World Bank December 4, Raya Elfadel Kheirbek, MD, MPH

Transcription

1 Alzheimer s Disease 1818 Society World Bank December 4, 2015 Raya Elfadel Kheirbek, MD, MPH

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3 The global impact of dementia Around the world, there is 9.9 million new cases of dementia in 2015, one every 3 seconds 46.8 million people worldwide are living with dementia in This number will almost double every 20 years Much of the increase will take place in low and middle income countries (LMICs): in 2015, 58% of all people with dementia live in LMICs, rising to 63% in 2030 and 68% in 2050.

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5 Cost The total estimated worldwide cost of dementia in 2015 is US$ 818 billion. By 2018, dementia will become a trillion dollar disease, rising to US$ 2 trillion by 2030 If global dementia care were a country, it would be the 18th largest Economy in the world exceeding the market values of companies such as Apple $ 742 billion and Google $ 368 billion

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8 More than 40 million people worldwide suffer from Alzheimer's disease, and that number is expected to increase drastically in the coming years. But no real progress has been made in the fight against the disease since its classification more than 100 years ago.

9 Alzheimer's now affects 40 million people worldwide. But by 2050, it will affect 150 million people If you're hoping to live to be 85 or older, your chance of getting Alzheimer's will be almost one in two. Already in the United States alone, Alzheimer's care costs 200 billion dollars every year. One out of every five Medicare dollars get spent on Alzheimer's. It is today the most expensive disease, and costs are projected to increase fivefold by 2050, as the baby boomer generation ages.

10 Alzheimer s Disease is the sixth-leading cause of death in the United States. among people age 71 and older, 16 percent of women have Alzheimer s disease and other dementias compared with 11 percent of men. 15 million Americans provide unpaid care for individuals with Alzheimer s or another dementia.

11 older African-Americans are about twice as likely to have Alzheimer s and other dementias as older whites, and Hispanics are about one and one-half times as likely to have Alzheimer s and other dementias as older whites.

12 Proportion of people with AD in the United States by age. Percentages may not total 100 because of rounding. Created from data from Hebert et al. [114]. A3

13 Projected changes between 2014 and 2025 in AD prevalence by state. Change from 2014 to 2025 for Washington, D.C.: -2.2%. Created from unpublished data provided to the Alzheimer's Association by Hebert et al. A1

14 What is AD? Alzheimer s disease is an irreversible, progressive brain disease that slowly destroys memory and thinking skills. Although the risk of developing AD increases with age in most people with AD, symptoms first appear after age 60 AD is not a part of normal aging. It is caused by a fatal disease that affects the brain.

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16 Inside the Human Brain To understand Alzheimer s disease, it s important to know a bit about the brain The Brain s Vital Statistics Adult weight: about 3 pounds Adult size: a medium cauliflower Number of neurons: 100,000,000,000 (100 billion) Number of synapses (the gap between neurons): 100,000,000,000,000 (100 trillion) Slide 8

17 Inside the Human Brain Other Crucial Parts Hippocampus: where short-term memories are converted to long-term memories Thalamus: receives sensory and limbic information and sends to cerebral cortex Hypothalamus: monitors certain activities and controls body s internal clock Limbic system: controls emotions and instinctive behavior (includes the hippocampus and parts of the cortex)

18 Inside the Human Brain Neurons The brain has billions of neurons, each with an axon and many dendrites. To stay healthy, neurons must communicate with each other, carry out metabolism, and repair themselves. AD disrupts all three of these essential jobs. Slide 14

19 Inside the Human Brain The Brain in Action Hearing Words Speaking Words Seeing Words Thinking about Words Different mental activities take place in different parts of the brain. Positron emission tomography (PET) scans can measure this activity. Chemicals tagged with a tracer light up activated regions shown in red and yellow. Slide 13

20 AD and the Brain The Changing Brain in Alzheimer s Disease No one knows what causes AD to begin, but we do know a lot about what happens in the brain once AD takes hold. Pet Scan of Normal Brain Pet Scan of Alzheimer s Disease Brain Slide 19

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23 Chromosome 21 People with familial AD have defect in Chromosome 21 Has the gene for the development of protein that causses theplaques deposited in the brain in AD Downs syndrome caused by mutation in chromosome 21 If a person lives 40 s, AD almost always is there

24 Environmental Factors? Studies in identical twins demonstrate environment does play a role Patients with head injuries are 3 times more likely to develop AD Aluminum salt ingestion Virus? Mother s age at birth Geographic distribution

25 Alzheimer's Disease Progression Beta-amyloid and neurofibrillary tangle formation begins in pre-clinical phase Cell death Pre-Clinical MCI Probable AD TIME Aβ=Beta-amyloid AD=Alzheimer s disease MCI=Mild cognitive impairment Asymptomatic Mild cognitive deficits Clear cognitive deficits Adapted from Shaw et al. Nature Reviews Drug Discovery. 2007;6:

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27 Symptoms of Alzheimer s Disease 1. AD begins with a pure impairment of cognitive function. mild cognitive impairment does not always lead to dementia. 2. Progression A. AD begins slowly. At first, the only symptom may be mild forgetfulness. In this stage, people may have trouble remembering recent events, activities, or the names of familiar people or things. They may not be able to solve simple math problems. They may begin to repeat themselves every few minutes in conversation. B. In the middle stages of AD, individuals may forget how to do simple tasks, like brushing their teeth or combing their hair. They can no longer think clearly. They begin to have problems speaking, understanding, reading, or writing. C. Late stage: AD patients may become anxious or aggressive, or wander away from home. Eventually, patients need total care. 27

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30 Why does the possibility of getting AD frighten you? Created from data from the 2014 Alzheimer's Association Women and Alzheimer's Poll. A17

31 Responses of Americans aged 60 years or older when asked which condition they were most afraid of getting. Created from data from the YouGov survey. A25

32 Burdens of caregiving among women providing around-the-clock informal care or 20 hours or less of informal care for someone with AD or dementia. *A great deal or good amount of strain reported. **Responded yes when questioned whether caregiving was causing marital strain. ***Responded 5 (very stressful) when asked to rate stress on a scale of 1 to 5. Created from data from the 2014 Alzheimer's Association Women and Alzheimer's Poll. A17

33 Impact on Caregivers Tasks Change Over Time Early stage Help with IADLS, eg, paying bills and preparing meals Cope with mood swings and reluctance to engage Mid stage Help with ADLS, eg, dressing and toileting Cope with increased memory loss, sleep disturbances, wandering, loss of driving Late stage Help with all personal care Cope with unresponsiveness and end-of-life issues

34 Consequences of caregiving on aspects of employment among female and male caregivers. Created from data from the 2014 Alzheimer's Association Women and Alzheimer's Poll. A17

35 National Support for Caregivers Alzheimer s Association Local chapters provide referrals to area resources and services, and sponsor the Safe Return Program, support groups, and educational programs: Eldercare Locator Nationwide service of the Federal Government helps caregivers locate local support and resources: Slde 40

36 Support for Caregivers Who are the AD Caregivers? Spouses the largest group. Most are older with their own health problems. Daughters the second largest group. Called the sandwich generation, many are married and raising children of their own. Children may need extra support if a parent s attention is focused on caregiving. Grandchildren may become major helpers. Daughters-in-law the third largest group. Sons often focus on the financial, legal, and business aspects of caregiving. Brothers and Sisters many are older with their own health problems. Other friends, neighbors, members of the faith community. Slide 37

37 Hospital stays per 1000 beneficiaries aged 65 years or older with specified coexisting medical conditions, with and without AD and other dementias, Created from unpublished data from the National 20% Sample Medicare Fee-for- Service Beneficiaries for 2009 [139].

38 Diagnosing AD Physicians today use a number of tools to diagnose AD: a detailed patient history information from family and friends physical and neurological exams and lab tests neuropsychological tests imaging tools such as CT scan, or magnetic resonance imaging (MRI). PET scans are used primarily for research purposes

39 Clinical Pearl THERE ARE NO TREATMENTS that can definitely stop loss of brain cells Medications are used to help slow the progress of cell loss and cognitive impairment associated with dementia 39

40 Treatment of AD Aricept Donepezil Celexa Citalopram Used to delay or slow the symptoms of AD Loses its effect over time Used for mild, moderate and severe AD Does not prevent or cure AD Used to reduce depression and anxiety May take 4 to 6 weeks to work Sometimes used to help people get to sleep Depakote Sodium Valproate Used to treat severe aggression Also used to treat depression and anxiety Exelon Rivastigmine Used to delay or slow the symptoms of AD Loses its effect over time Used for mild to moderate AD Can get in pill form or as a skin patch Does not prevent or cure AD

41 Treatment Cont ed Namenda Memantine Razadyne Galantamine Zoloft Sertraline Trileptal Oxcarbazepine Tegretol Carbamazepine Remeron Mirtazepine Used to delay or slow the symptoms of AD Loses its effect over time Used for moderate to severe AD Sometimes given with Aricept, Exelon Does not prevent or cure AD Used to prevent or slow the symptoms of AD Loses its effect over time Used for mild to moderate AD Can get in pill form or as a skin patch Does not prevent or cure AD Used to reduce depression and anxiety May take 4 to 6 weeks to work Sometimes used to help people get to sleep Used to treat severe aggression Also used to treat depression and anxiety Used to treat severe aggression Also used to treat depression and anxiety Used to reduce depression and anxiety May take 4 to 6 weeks to work Sometimes used to help people get to sleep

42 Education of Patient and Family Safety issues: Home environment Driving Medication adherence Financial exploitation Elder abuse Address future needs: financial planning, advanced directives, power of attorney

43 Education of Patient and Family Medications Define treatment success Symptomatic benefit in Cognition Physical function and ADLs Behavior Increases time to nursing home placement Discuss length of therapy Adequate trial is 6 months Cummings JL. Am J Geriatr Psychiatry. 2003;11(2): Doody RS, et al. Arch Neurol. 2001;58(3):

44 Education of Patient and Family Alzheimer s Association 24/7 Nationwide Helpline Information and referral in 170 languages Current reliable information for healthcare professionals, people with dementia, family members and caregivers 300 local offices Information and referral Support groups Care consultation Safety services Education, local conferences

45 The Future of Alzheimer s Disease Earlier recognition Dependent on reliable biomarkers New medications Current medications only address symptoms New medications in development Disease-modifying therapy Combination disease-modifying and symptomatic therapy Prevention

46 The Future of AD Failure rate for Alzheimer s disease drugs during was 99.6% Clinical trials currently being conducted Drugs in development aim to prevent or modify AD itself Need more patient volunteers and federal research funding Alzheimer s diagnostic tests inch forward, but treatments are still lacking Harrington, Rebecca. Scientific American. 27 Feb Available from:

47 AD Research: New NIA Study The NIA is launching a new research partnership, called the Neuroimaging and Biomarkers of AD Initiative, to study how the brain changes in Mild Cognitive Impairment (MCI) and AD. Using MRIs and PET scans conducted at regular intervals, researchers hope to learn precisely when and where in the brain problems occur. Researchers will also examine blood samples to check for higher levels of abnormal substances that could be considered biomarkers of AD.

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49 In the year 1901, a woman called Auguste was taken to a medical asylum in Frankfurt. Auguste was delusional and couldn't remember even the most basic details of her life. Her doctor was called Alois. Alois didn't know how to help Auguste, but he watched over her until, sadly, she passed away in After she died, Alois performed an autopsy and found strange plaques and tangles in Auguste's brain -- the likes of which he'd never seen before.

50 Now here's the even more striking thing. If Auguste had instead been alive today, we could offer her no more help than Alois was able to 114 years ago. Alois was Dr. Alois Alzheimer. And Auguste Deter was the first patient to be diagnosed with what we now call Alzheimer's disease. Since 1901, medicine has advanced greatly. We've discovered antibiotics and vaccines to protect us from infections, many treatments for cancer, antiretrovirals for HIV, statins for heart disease and much more. But we've made essentially no progress at all in treating Alzheimer's disease.

51 I'm part of a team of scientists who has been working to find a cure for Alzheimer's for over a decade. So I think about this all the time. Alzheimer's now affects 40 million people worldwide. But by 2050, it will affect 150 million people -- which, by the way, will include many of you. If you're hoping to live to be 85 or older, your chance of getting Alzheimer's will be almost one in two. In other words, odds are you'll spend your golden years either suffering from Alzheimer's or helping to look after a friend or loved one with Alzheimer's. Already in the United States alone, Alzheimer's care costs 200 billion dollars every year. One out of every five Medicare dollars get spent on Alzheimer's. It is today the most expensive disease, and costs are projected to increase fivefold by 2050, as the baby boomer generation ages.

52 It may surprise you that, put simply, Alzheimer's is one of the biggest medical and social challenges of our generation. But we've done relatively little to address it. Today, of the top 10 causes of death worldwide, Alzheimer's is the only one we cannot prevent, cure or even slow down. We understand less about the science of Alzheimer's than other diseases because we've invested less time and money into researching it. The US government spends 10 times more every year on cancer research than on Alzheimer's despite the fact that Alzheimer's costs us more and causes a similar number of deaths each year as cancer

53 The lack of resources stems from a more fundamental cause: a lack of awareness. Because here's what few people know but everyone should: Alzheimer's is a disease, and we can cure it. For most of the past 114 years, everyone, including scientists, mistakenly confused Alzheimer's with aging. We thought that becoming senile was a normal and inevitable part of getting old. But we only have to look at a picture of a healthy aged brain compared to the brain of an Alzheimer's patient to see the real physical damage caused by this disease. As well as triggering severe loss of memory and mental abilities, the damage to the brain caused by Alzheimer's significantly reduces life expectancy and is always fatal.

54 Remember Dr. Alzheimer found strange plaques and tangles in Auguste's brain a century ago. For almost a century, we didn't know much about these. Today we know they're made from protein molecules. You can imagine a protein molecule as a piece of paper that normally folds into an elaborate piece of origami. There are spots on the paper that are sticky. And when it folds correctly, these sticky bits end up on the inside. But sometimes things go wrong, and some sticky bits are on the outside. This causes the protein molecules to stick to each other, forming clumps that eventually become large plaques and tangles. That's what we see in the brains of Alzheimer's patients.

55 We've spent the past 10 years at the University of Cambridge trying to understand how this malfunction works. There are many steps, and identifying which step to try to block is complex -- like defusing a bomb. Cutting one wire might do nothing. Cutting others might make the bomb explore. We have to find the right step to block, and then create a drug that does it.

56 05:20 Until recently, we for the most part have been cutting wires and hoping for the best. But now we've got together a diverse group of people -- medics, biologists, geneticists, chemists, physicists, engineers and mathematicians. And together, we've managed to identify a critical step in the process and are now testing a new class of drugs which would specifically block this step and stop the disease.

57 5:43 Now let me show you some of our latest results. No one outside of our lab has seen these yet. Let's look at some videos of what happened when we tested these new drugs in worms. So these are healthy worms, and you can see they're moving around normally. These worms, on the other hand, have protein molecules sticking together inside them -- like humans with Alzheimer's. And you can see they're clearly sick. But if we give our new drugs to these worms at an early stage, then we see that they're healthy, and they live a normal lifespan. This is just an initial positive result, but research like this shows us that Alzheimer's is a disease that we can understand and we can cure.

58 After 114 years of waiting, there's finally real hope for what can be achieved in the next 10 or 20 years. But to grow that hope, to finally beat Alzheimer's, we need help. This isn't about scientists like me -- it's about you. We need you to raise awareness that Alzheimer's is a disease and that if we try, we can beat it. In the case of other diseases, patients and their families have led the charge for more research and put pressure on governments, the pharmaceutical industry, scientists and regulators. That was essential for advancing treatment for HIV in the late 1980s. Today, we see that same drive to beat cancer. But Alzheimer's patients are often unable to speak up for themselves. And their families, the hidden victims, caring for their loved ones night and day, are often too worn out to go out and advocate for change. So, it really is down to you. Alzheimer's isn't, for the most part, a genetic disease. Everyone with a brain is at risk. Today, there are 40 million patients like Auguste, who can't create the change they need for themselves. Help speak up for them, and help demand a cure.