Proliferating so fast throughout the globe. And according to dr. Marie menard, who we will hear from, the number is estimated to grow to 115 million by 2050 as populations around the world age, although there is early onset as l but predominantly it is one of the byproducts of all of us ages and there seems to be a higher proclivity the woolder one gets. Once someone reaches 85, the chance of some form of dementia is one out of two. The total cost of addressing this is 818 billion. But as early as next year it is estimated that this cost will rise to at least 1 trillion. Thats per year. It will go up from there. As we all know, alzheimers is a cruel disease robbing its victims of their memories and their identities. Robbing their family and friends of the person they know and love. It is excruciatingly painful for someone who lose themselves gradually. I have spoken myself to many individuals, especially those who are early onset who have young families and are dealing with the agony that they know it is progressing. There is no cure. There are drugs, five of them so far and others that are in the pipeline that treat symptoms, but theres no actual cure. And so it is very tough. It takes a very heroic person to cope and manage with that. We also know that the families have to deal with a very painful ordeal as well. The caregivers, the loved ones, the family and the friends. In 1999 along with congressman now senator marquis i cofounded the Correctional Task force on alzheimers which i still cochair today to bring this disease to the forefront of the congressional agenda. To advance support for federal research and to increase awareness. The task force worked in partnership with the Alzheimers Association to unanimously pass the national alzheimers project act which established a variety of experts to work with the secretary of hhs to assess and address Alzheimers Research, institutional services, and home and Community Based care with the goal to identify a cure or disease modifying therapy for dementia by 2025. Today there are over 170 members of the house and senate in the task force. This year we work very hard in a bipartisan way to get an increase of some 414 million to the Alzheimers Research funding at nih. Under hhs appropriations chairman extraordinary leadership the fiscal year 2018 was enacted and passed in september of this year including the 400 million increase for Alzheimers Disease Research at the National Institutes of health. This would bring total funding to 1 1. 8 bill. And nih spending is almost tripled since fiscal year 2015 when 58 589 million was allocat for sufch research. Shockingly the majority of people with alzheimers or other forms of dementia have not received a diagnose diagnose diagnosis. Its even truer in the developing world. Michael points out in his testimony today that detection and diagnosis are a stubborn problem everywhere. Research shows that most people currently living with dementia have not received a formal diagnosis he will testify, and high Income Countries, 20 to 0 50 of dementia cases are recognized and documented in primary care. This treatment gap is great ner low and middle Income Countries without a diagnosis there cant be treatment, care, or organized support or the opportunity to volunteer for clinical research. Even when alzheimers or other forms of dementia are diagnosed, care is too often fragmented, uncoordinated and unresponsive to the needs of People Living with this. The response introduced the Health Outcome planning education or hope for alzheimers act of 2015 to provide Medicare Coverage for Care Planning session for patients newly diagnosed with alzheimers ze alzheimers disease. In recognition of this the legislation garnered 310 bipartisan cosponsors. Ultimately medicare adopted an amended version of the hope of actually an improvement for final rule for calendar year 2017s physician fee scheduled. It robs the victims not only of their memories, but also their awareness, but also their lives. In the american journal of Public Health, Research Survey years of left lost between the number of deaths between 1995 and 2015, annual deaths due to alzheimers ple alzheimers complications in the u. S. Rose from 20,607 in 1995 to 110,568 in 2015. During that period alzheimers rose from the 14th leading cause of death among ailments in this country in 1995 to number six in 2015. For the record, this is my fourth hearing ive chaired on alzheimers disease. On june 23rd in 2011 we held a hearing on the global strategy to combat the Devastating Health and Economic Impacts of alzheimers. On november 21st we held a hearing on the g 8 dementia summit and beyond. In 2014 on the actual summit report from the g 8 and now in todays hearing of course. Todays hearing is intended to examine the existing potential options for prevention and treatment of this often this always devastating disease. And the statistic cited earlier likely will be more worse in the and records of victims and of deaths. As our hearing testimony will demonstrate, there is hope for alzheimers patients, their families and friends. There is a surge for research. For example, Research Team from columbia universitys Medical Center in 2013 said they had traced alzheimers to the early developmental stages. In science translational medicine two years ago, australian researchers planed a none invasive Ultrasound Technology that clears the brain of neuro toxic plaques, structures that are essential for cognitive function. By 2016 scientists at the university of zurich said they were amazed to find that their patients treated with the highest dose of an antiby on witness today will tell us more about these and other advances that again the United States is walking point in the world. In this and we had two tremendous witnesses and experts who are doing their best and their staffs to make sure that we get their sooner rather than later. I would also point out for the record this congress ive joined my colleagues in introducing the bold act which would establish centers of excellence and it is designed to really take this to the next to have congressional support for this effort in a robust way. Ive also reintroduced a law passed last year in the house t. Deals with the wandering issue. We know that when alzheimers or autism individuals have the bracelet, theyre found usually within 30 minutes. When they dont and they go wandering, it can be catastrophic if not a cause of death from drowning and a whole host of other reasons if they are not rescued from that wandering. Next week i will reintroduce the global rain health act to increase research on prevention and treatment of autism. And alzheimers and other forms of dementia. This legislation which i first introduced in 2015 would encourage the building of treatment capacity for these Brain Disorders among caregivers in developing countries and support and increase International Cooperation and implementation of strategies on prevention and treatment. Id like to now yield to the doctor for any opening comments. Thank you, mr. Chairman. Thank you for having this hearing. It obviously is incredibly important. Anytime you can say neuro toxic plaques in congress, thats a good day. As a physician. So im trained in internal medicine and taking care of many alzheimers patients. The urgency of addressing this skp issue and looking for ways to mitigate the disease but ultimately looking for ways to reverse and cure disease are obviously our ultimate goals. I think we often focus here domestically on what we need to do to help address this issue. But i work pretty closely with our Alzheimers Association and i think the Alzheimers Association has done a wonderful job elevating the level of dialogue but also elevating the dialogue on, you know, why this is a global epidemic. Often when we think about Global Health were thinking about the Communicable Diseases that are out there, but there really is, as there are more developed nations, weve got to spend more time thinking about the impact of noncommunicatable diseases like alzheimers disease. As we start to think about those Public Health approaches, from my Public Health background, theres a number of things that are the lifestyle modification, the things you can do to slow down and mitigate disease. A second step is building the Public Health infrastructure in the Global Community to help both families and patients manage and navigate that disease. Again, i do think we are going to see this coming tidal wave as people live longer in the Global Community, the lack of infrastructure and the lack of readiness to, you know, manage this tidal wave of folks with dementia and with alzheimers disease and other noncommunicatable diseases for that matter. And then long term this is a global challenge. I look forward to hearing from the witnesses, you know, we can quantify the direct costs of alzheimers, but then also the indirect costs of alzheimers in terms of, you know, both the patient as well as the impact on families and caregivers. And then ultimately part of the reason why i am such a strong advocate for making the investments in the nih and making investments in research is the return on that investment, if we are able to find a cure or even better therapies to mitigate disease and slow down disease is going to be, you know, pretty significant significant. If we dont, we will be spending billions upon bills of dollars on the back end. This isnt just a u. S. Challenge. This is a global challenge. Mr. Chairman, i think this is incredibly timely topic. I look forward to hearing from the panelists. So thank you. I yield back. Thank you, doctor. Id like to yield for any comments you might have. Thank you for conducting this very important hearing. Many of the things this committee does deals with diseases and things people are suffering from that we dont suffer from in this country. When i came to congress, at 58 years old i had my very first baby. The mother describes her as my very last baby, by the way. But so all of a sudden Maternal Health and infant health, prenatal care became so important to me because it was personal to me. And i always say that on yellow Rose Katherine was, she hit the birth lottery. She was born on may 19th of 2015 on the same day tens of thousands of other children were born. Except she was born on Staten Island in new york city and has every one of her vaccinations, every one of her well visits, and children born that same day who didnt hit that birth lottery, didnt have the same advantages she did. So thats a lot of things that this committee has done thats been personal to me. I am also the only son of an alzheimers patient. My mother died the year before i was elected after suffering for four years. I was blessed. I had her until she was 89 years old. And her mother died when she was nine, so i always say i had my mother for 50 more years than she had her own mother. But i watched this woman become someone i didnt know. A woman who was always calm who became violent. A woman who would sit and just stare even when you were speaking to her because she could no longer communicator understand what you were saying. I learned a lot about the disease. Not as much as my friend dr. Bera, but about the proteins that grow on peoples brains and advancements in medicine that is finding ways to slow that growth down and maybe stop it and maybe at some point that can remove the proteins from peoples brains that may cure the disease is our hope. I know that we gave the National Institute of health in the 21st century cures act billions of dollars to help the advancement of some treatments and cures for things like alzheimers. I just wanted to tell my personal story just so i could tell you how much i appreciate you being here and how important this is in a Global Health environment but how personally y its touched me. I thank you for being here. Thank you very much. Let me introduce our distinguished witnesses. Beginning with dr. Bernard who serves as Deputy Director of the National Institute on aging at the National Institute of health. Dr. Bernard serves as the principle adviser to the nia director working closely with the director in overseeing approximately 2 billion in Research Conducted annual lie by the institute. She chairs two department of health and human services, healthy people, 2020 objectives, older adults and dementia, including alzheimers disease. I will then hear from dr. Roger glass who id point out is also from new jersey. Ornl originally from summerville new jersey. He serves as the Society Director at the National Institutes of health. Dr. Glass has maintained field studies in india, bangladesh, pra z brazil. And elsewhere. Has received num roerous awards. And the charles dr. Charles award of the for Infectious Diseases. Two experts and two very much welcomed witnesses to our subcommittee. Good afternoon, chairman smith, representative bera, representative donovan. Im happy and honored to represent the National Institute on aging, one of the 27 institutes and centers of the nih. We lead Alzheimers Disease Research. I bring my experience as an academic geriatrician. I can empathize with the prevalence on this illness and the impact it had on families. When i saw patients on a daily basis, it was heartbreaking to see the impact it had on those patients and on their Family Members and to recognize that i didnt have much that i could bring to the care of those individuals at that time. Its encouraging to be at nih at this point and to see the blossoming of more and more information thats developed with Global Partners, that will hopefully get us to the point that we will have a prevention or cure for this illness. We have, in fact, over the decade, supported a number of International Studies that have led us to a greater understanding of the illness. I will spend what time is allocated to me to briefly highlight three of those. First, were making significant advances in our understanding of the course of alzheimers disease from our health and retirement study. This is a 20yearold national sampling of older adults in the United States. People 50 years of age and older who have followed through to their death. And it has allowed us to see the ns natural course of aging as well as the natural course of the development of alzheimers. This study has had a new component added thats an international component. The h cap. We have the hope that if we can get researchers across the global to harm onnize the way they go about cognitive assessments, we will be able to better know the course of the illness and to sort out the genetic social environmental influences that impact alzheimers disease. Were supporting the deployment of hcap and hrs and health and retar retirement studies as well as a smaller scale study in south africa. This will provide us some unprecedented scientific opportunity. A second important need is for means to make the diagnosis of alzheimers earlier than the current standard which is when a person has cognitive and functional problems. There are many promising new findings, particularly as a results of something called the alzheimers disease. Adney is a world wiwide collaboration. It has led to the identification of biomarkers, proteins and images of the brain that allow us to measure on the set and progression of this disease. A decade ago the only way that you could definitively say that someone likely had alzheimers disease was by autopsy. But now we can see in a living brain the deposition of plaque in an individual and follow its course before they have clinical symptoms. As we make progress of validating this and other biomarkers, we hope to translate this into useful clinical tools. Third, and i supportive investigators have been conducting tre conducting treatment trials that have a global reach. One such study which has received quite a bit of attention is the disease trial involving the Worlds Largest group of alzheimers disease. Approximately 300 Family Members in the country of colombia who share a mutation that guarantee by middle age theyll have alzheimers system. Were very grateful to this family and all participants in alzheimers disease and related trials. They are true heroes who have allowed us to learn and continue to learn about this disease. Finally id say that my patients would tell me every day they did not want to grow older if they did not have their cognitive capacity because they did want want to become a burden to their families. With, we Global Partners are working to develop answers to their concerns. The global rise of alzheimers prevalence, the situation is urgent as you have well articulated and were using every possible approach to diminish the impact of this disease as happen rapidly as po. Thank you for allowing me to testify skand i look forward to your questions. Thank you for your testimony and your insights. Dr. Glass. Thank you. Good afternoon, chairman smith. Acting Ranking Member bera and distinguished member donovan. I too had a father with alzheimers and i sympathize and went through the same experience. Im roger glass. Im the director of the fog ar Tee International center at the National Institute of health. Im honored to join my colleague in discussing how were confronting the burden of alzheimers disease. Diseases like alzheimers know no borders. People suffer from this disease and will benefit from treatments and cures. We need to find the brightest minds everywhere to assist in this endeavor as well as to identify populations with unique environmental or genetic risks because the High Quality Research that we do doesnt happen only in the United States. It happens elsewhere. In order to take advantage of these international situations, we need the best trained scientists with high ethical standards, with good Data Management capabilities, with laboratories capable of conducting the research thats absolutely essential. Fogarty facilitates building these Research Partnerships leading to capacity, billing capacity for researchers internationally to create the next generation of scientists who will address the alzheimers condition. These scientists who will address these problems in the future are just being trained today. As dr. Bernard mentioned in her remarks, nia is supporting the study and n colombia of an extended family with a genetic mutation for familial alzheimers. This family is center fstage fo much of our research on alzheimers. This Partnership Began in the early 1990s when an american investigator then at harvard met a colombian physician, dr. Lopero. He had a patient with alz hiemers ahie alzheimers and found that the patients father and grandfather had alzheimers. Because of his curiosity as a young physician, not a researcher, he searched out and developed a cohort of 5,000 people with this genetic problem. It was from this conversation six years later of these american and colombian investigators that they began a decade long collaboration to look and see what they could learn about the epdeemology and jeanet genetics of alzheimers. That has proved incredibly fruitful. In the 1990s these doctors received a grant to Work Together. By 2004 and 07 the National Institute of aging and fogarty were both engaged in this research. This researched not only following up, but training people in Laboratory Methods n building capacity so that we could actually conduct Quality Research under the best ethical standards in the field. At the same time, it also engendered collaborations between communities that were invested. These were not patients in colombia. Preparing to conduct for scientists to conduct highimpact research is critical to the fogerty agenda. And what began as a partnership between these two scientists, individual scientists, is now the cutting edge of whats become 100 million Clinical Trial. The first in the world for early prevention of the progression of alzheimers disease. Its a unique study that couldnt be done anywhere else, and this cohort has really an incredible finding and discovery. Its an essential part of the Research Team as is the laboratory in colombia. Colombia is not unique in this. While the topic of todays discussion is alzheimers disease, the fogerty center has also been involved in many other neurologic problems. Such as the search and research on cerebral malaria, neurological hiv, hydrocephalous, chronic psychotic disorders in tanzania nia and stroke outcomes. Fogerty takes science where the problems are. And where the opportunities are for the most rapidly accelerating advances in research. And we also are concerned and developing true partnerships for research and advancing capacitybuilding. Like dr. Low pera, a unique investigator in a unique setting, with a unique population of this familial alzheimers disease, thats leading us to hopefully more rapid cures. From this partnership and with nih support, were already advancing discovery research. Were already working in basic research in colombia in collaboration with the u. S. The group in colombia are now an integral part, an essential part, of the u. S. Research endeavor on alzheimers. And the results of this endeavor, both for the u. S. Population and for the population in colombia and around the world, will all benefit from this activity. Fogerty is essential for building these International Collaborations and we work very closely with nia and other institutes at nih to do this Important International collaboration. Thank you very much. Dr. Klaas, thank you very much for your testimony and leadership, as well. Let me just ask the question with regards to imaging. What kind of brain imaging are we talking about . C. A. T. Scan, mri . Obviously that is not available in most developing world settings. Right. And since there is such a large numbers of people never get a diagnosis, about 50 or less in the United States, how quickly is this technology being advanced so more people will get, you know, a definitive earlier on so some of these drugs that, again, only deal with symptoms can be applied to mitigate those symptoms . So what i was describing is opportunities with imaging and looking at proteins are meant to be in the Research Setting currently. But they are being refined and were beginning to look at things in the blood, in the peripheral blood, changes in smell. Things like the development of depression symptoms years before a person actually has dementia as things that will help us to be more precise in making that diagnosis clinically. So it all comes together to help us. We dont quite have something that can be translated directly from the research lab that is anything better than we currently have in terms of looking for symptoms right now. And just let me ask you. You mentioned dr. Glass, about the uganda situation with hydro self allic foundation. We had doctors develop a shunt intervention to help people who have water on the brain. And its amazingly effective. And not much by way of having to redo it. You mentioned risk factors. Obviously, genetics is a risk factor. We all know that. And one of the studies you mentioned thats a big focus. But when you talk about environmental risk factors, we know that in the area of autism, environment does play a very serious role. And nih has chronicled that in its reports. Im wondering if other areas of investigation are being pursued, including toxic chemicals of various kinds. Lyme disease. I chair of the lyme disease caucus, as well. And its a huge problem in my district. In my state. And in our region. Grossly underreported. And there have been studies that found that people with lyme that dementia was one of the consequences. And im wondering if thats being looked at. So if you could speak to the environmental side of it, if you would. Lets all start off and say that from the environmental perspective, yes, we have a number of studies that are looking at various environmental toxins that may be contributing to problems with the development of alzheimers. Thats particularly assisted by projects that are looking at people in the longterm and looking at what has happened to them. Were also looking at education, looking at diet. Looking at geographic location. All of those may contribute. I quite honestly do not know specifically about lyme disease. We could look back and get back to you on that. But a variety of things environmentally and socially seem to be associated with differences in the frequency with which various groups have alzheimers disease. Dr. Glass . I dont know of other risk factors for alzheimers. Although hispanics have an increased risk and an earlier presentation. But for other neurologic disease, we know a lot about infections like malaria and hiv, and other meningitisties. Heavy metals and exposures. We know about foods in africa, for instance, like manny okay which has a sigh need and leads to poisoning and alcohol and fetal alcohol. So there are other toxins. But for alzheimers, dont have those yet. And we could look and provide that information. I appreciate that. For the record. The International Response has become increasingly aggressive and robust. In 2012, w. H. O. Released a document, dementia, Public Health priority. And i and greg simkins and others on our subcommittee met with margaret chen, w. H. O. Director general. And she had a real heart for this, as do so many others at the w. H. O. In 2013, the g8, now g7 committed to more research funding. And thats canada, france, germany, italy, japan, russia, United Kingdom and, of course, the United States. And im wondering if you could tell us that, plus the newest 2017 w. H. O. Action plan. Paho has a plan. People seem to be coming up with action plans, and thats all great. But how well are they being implemented. Are other countries, for example, like we are. We are tripling our nih funding. Cole has done a wonderful job. Hes got a heart for this. The Alzheimers Association never lets up in pushing this and having a great impact. You know, in my own state, Christine Hopkins is the alzheimers ambassador. We all have one. She is constantly in contact with me, and i think that is a great way of advocating on behalf of patients and caregivers. Katie maclin is the director in our area, and i was just at a march for alzheimers in bradley beach. There was over 1,000 people. So the Alzheimers Association are here, and will be submitting testimony, as well. You know, really pushing for the private sector to come up with money. August mentalitying, of course, and ledge rajjveraged by the pu sector money. Is japan, is germany, the uk, the other g8, the after fluent countries, coming up with resources so synergistically well see a great surge in research . So i could certainly say that we track whats happening internationally in something that was developed jointly with Alzheimers Association, something called the international Alzheimers Disease Research portfolio. That allows us to see across the globe whats going on. It currently has more than 8,000 projects. Representing 30 funding agencies. 11 different countries. We also work through the department in being responsive to what the World Health Organization is doing to work across the globe in alzheimers projects. And we are aware that various countries have developed plans as we have. So i would probably defer to my colleague, dr. Glass, for further elaboration. Most important risk factor for alzheimers is age. And we see aging in the population around the world, which is why this has become such a tremendous problem as we look forward. And i think its because of that aging that many groups including the japanese and the english, have invested in this heavily. I think as new diagnostic methods become available, so you can actually make a proper diagnosis, the importance of alzheimers globally will be observed in each of the countries that does the surveys. And so its with the improvement of diagnostics that dont require a dead brain that well be able to understand the prevalence and increasing incidents over time. Just two final questions. Is there a best estimate if things dont change, where we will be by 2025 and 2050 . I gave one estimate, and theres highs and lows, of course. They were all guest estimates. Do you think we will reach the goal of a diseasemodifying therapy by 2025, which is the w. H. O. Push, which is our push, that we all got behind and pushed a couple years ago. Do you think well get there. Is there enough Critical Mass in resources to get us there . I would certainly say were very grateful for the Additional Resources that have been provided. And again, as a clinician, im really excited. Because theres been the opportunity to invest broadly. Basic research that will help us to better understand whats happening mechanismcally with this illness. Explosion of recognition of genes related to it. We went from only knowing four genes a decade ago to more than 24. Lots of clinical studies. 100 or so. With results coming out in the next many years that will help us to understand which direction we need to go. Enhancement of populationbased studies that will help to answer questions you were asking about toxic exposures and social factors, et cetera. So i think that theres great momentum going on. And well have to see. I would concur. We have more tools to research alzheimers today than we have ever had. When my dad passed away, we have imaging techniques which are extraordinary. Genetics, genetic entrees to the disease. Testing out new drugs. And so were in a position better today than ever before to accelerate the advance. The fact that we have so many monday els in Clinical Trials and drugs being tested. Could any of them delay the progression of the disease, they will have a huge impact on the cost of care. So i think in the short run, we have Clinical Trials that are ongoing now. Also, the trial in colombia. If its successful, we will all benefit. If it fails, it will tell us that were barking up the wrong tree. And we need to find other targets that would be more susceptible to for new drugs. So either way, i think were on a role that we never had before, and the opportunities are clearly before us. As i mentioned in my opening, ill be reintroducing the Global Health care act brain health bill next week. It deals with three diseases. Autism, alzheimers and hydro self allic condition, referencing what you mentioned about uganda, dr. Glass. It concerns me that usaid and ive had conversations with mark green, new administrator. Its important we do Infectious Diseases, clinical diseases, by brain health has been left to cdc and diplomacy area, not to the assistance at the country level. So my hope is we will be able to get this bill passed and begin moving in the direction of funding those kinds of initiatives, as well. Dr. Burr. Thank you, mr. Chairman. Dr. Bernard, you talked about longitudinally following older americans. As youre building this database and looking at that database and now adding in folks from around the world, as well as in that database, what kind of patterns are has it been around long enough and what types of patterns potentially are emerging . Thank you for asking that question. What were seeing is in the United States, at least, that the incidence of alzheimers disease may be decreasing in certain segments of the population. Whether thats because of better education, better Blood Pressure control, better nutrition, we dont know. But were seeing other sorts of things, like were being able to determine that if you make it to age 70, without cognitive impairment, that you still have as a man almost one out of four chance of developing alzheimers. As a woman, one out of three chance of developing alzheimers disease. And were seeing when we compare across countries that there seems to be a social economic status relationship. The higher the social oeconomic status, the longer one puts off the likelihood of developing an alzheimers type dementia. So there is clearly a social component to this. And we are looking forward to further disentangling that. Do you see a pattern with level of Educational Attainment. So lower rates of alzheimers disease in folks with higher Educational Attainment . It appears that the that there is such a correlation. That the rate of the development of the disease, the age at which one develops the disease, is the rate is lower, the age at which you develop is older. So there seems to perhaps be some sort of protective or beneficial effect of education. So when i used to practice medicine, i would tell my patients to do cross word puzzles every day. It wasnt just something that i was telling them to do in terms of exercising your brain and going to distant memories. Yeah. We have a number of studies where were trying to really disentangle exactly what makes the difference. Whether its doing cross word puzzles or the brain games are out there, et cetera. We dont have definitive evidence thats truly impactful. We do have one study, something called the act study, that demonstrated that if you trained people in a particular component of cognition, that that was beneficial for that component. Like speed of processing of information or memory or things like that. But its not clear that it truly can put off dementia. In fact, we had the agency of health, research and quality and the National Academy of science, engineering and medicine to look at that very carefully for us recently. And their assessment was that we are not yet at the point that we can say definitively those things will be recommended to patients will make a difference. But it certainly cant be harmful. And particularly if theyre enjoying those sorts of things. I do the same sort of thing, as well. Dr. Glass, do you want to add anything in addition . Again, as we do when we do medical research, were creating this huge database, and were looking for patterns. In terms of risk stratification now, as, you know, we try to come up with better diagnostic tools, what are some of the, you know outside of Family History of alzheimers, where are some risk factors that we ought to be thinking about, and educating the public on . And certainly educating our physicians on, as well, at our work force . So certainly, it appears that people who are likely to develop an alzheimers type dementia are the people who live for a longer period of time. The people who may not have as high a level of education. People who have had problems with high Blood Pressure and diabetes and thats the reason some of the populations that are considered to be underrepresented populations in the United States may have a higher prevalence, as dr. Glass alluded to. There may be some role for past significant head trauma. Things of that sort. But, you know were not we still havent quite seen definitively those patterns emerge out of the database. There are risk factors that we have seen, whether they are modifiable risk factors is the question. Okay. Let me just add, congressman barrett, dr. Barrett, even within the colombia cohort, which comes from a single founder, there are genetic mutations that have been introduced over the last 200 years. So that the age of onset, the speed of progression, are all i had osink sees, differences, that we can understand by linking the genetics with the phenotype and with the progression. So we can actually learn a lot about the genetics and by plotting those individuals. So i think theres when we deal with the melting pot of the United States, with genes that have been mixed from all over, much more difficult to do. And i think that well learn a lot more from this cohort and perhaps from others, which have these familial modifications. Dr. Bernard, with a Family History of alzheimers disease, what is the risk of developing alzheimers disease . Can we say definitively . What we can say is that if you have an 4 gene or two versions of the april e 4 agage you have a high risk. We cant say there is a 100 likelihood but a high risk of developing alzheimers disease. If you have a protein mutation, those are associated with early onset alzheimers disease. They tend to be auto so manial dominant meaning likely youre going to develop alzheimers disease associated with that. And then just to simply a Family History, yes. I mean, if you have Family Members who have had an alzheimers type dimension i cant, you may be at greater risk as well. Whether its related to one of those other genes that we have discovered of late, or a combination of the genes or environmental factors or social factors, its not totally clear at this point. In terms of risk stratification, so patient presents with the Family History of alzheimers disease, how readily available are the genetic testing and, you know, again, just to try to think about risk stratifying . So i think that there are private entities that are available that can do the genetic testing. We certainly have a system alzheimers Disease Centers that are set up to bring people in to participate in research programs. And some of these centers are focusing on people who have genetic risk. And i again would put a plug in for people to be involved in such things. We need lots of different people. A diversity of people involved in these studies to really understand what how it is going to present in different groups. And do we know, are there any prospective studies going on right now where youre taking folks with a confirmed diagnosis of alzheimers type dementia, taking their Family Members and prospectively following those Family Members, looking for patterns . Are those studies ongoing . So we have a number of studies that are looking at people who by a bio markers they have the chains in the brain. They may have a genetic abnormality, but are not yet symptomatic. And were looking at various interventions to try to make a difference in their outcome. So to that degree, yes. And at this stage, with what we do know, theres nothing that prevents us from educating our Health Care Work force. If someone has that Family History of alzheimers disease, you know, they ought to look at those other mitigating factors. Manage their subsididiabetes be look at alcohol consumption. And, be again, other mitigating factors that may not prevent them from developing alzheimers, but may slow down the evolution of the disease. Look at maintaining brain activity through, you know, whether its, you know, brain games or crossword puzzles or maintaining physical well being. Those are all reasonable interventions that we can do that probably have a cost benefit. But also, you know is that an accurate statement . I think thats a fair statement. That National Academies and the agency of health and research and quality study that i reference, they said we do not yet have definite evidence, but there is encouraging inconclusive evidence that controlling Blood Pressure and hyper tenses, physical activity can make a difference. And inconclusive, but possibility for cognitive engagement. So, yes, i would hope that my colleagues, your colleagues, would do all of the things that you had mentioned, as well as encourage those patients to think about getting involved in a clinical study. Right. I would ask 100 more questions, but i will yield back. Thank you. Now that dr. Barra has made dr. Glass and myself feel real comfortable about asking about Family History of having two patients who have history of alzheimers. I want to ask about were talking about studies and being able to diagnose. And doctor, i remember when they say you needed an autopsy to actually do a diagnosis. I remember that. Are we advancing also in how were treating patients now with alzheimers, as were waiting for the studies to conclude and how advanced have we gone . I cant believe what you said in your testimony about i think identifying four genes ten years ago or so. Now we could identify 24. Thats an incredible advancement for the person on the panel who is not a physician. So has our treatment gotten better as your studies have advanced and developed . So we unfortunately do not have a true treatment. We have drugs that can slow down symptoms for a period of time. But it really doesnt change the course of the illness. So at the same time that we are vigorously looking for that prevention or cure, were also supporting research thats looking at being more effective at caring for the individual with alzheimers disease and for their care giver. In fact, on the nih campus just last month, there was a summit on alzheimers care giving with some 500plus researchers, advocates, People Living with dementia. And it was really edifying to hear them reviewing whats there, and noting that we have a lot of interventions that are effective and can be generalized. There are opportunities for further enhancements there. Some 450 recommendations came from that study. So we are sifting through that and seeing what we can do to further enhance things. But i would like to think that we are further down the road in terms of paying attention to issues of caring for individuals of alzheimers and for their caregivers. Theres still room for further improvement. Anything to add, doctor . Im sorry. Not really. It would be nice that we had a cure. There are certainly cultural differences in giving care. And keeping people at home versus in institutions. Definitions that people use. Weve supported research on caregivers in the Spanish Language, because the way you make a clinical a clinical diagnosis based on history is linked to the terms that are used for dementia. And for accepting it as a disease. And i think thats an area where were learning. But not breakthroughs as such. Just in the caregiving. Quality of caregiving. I certainly understand that. My mother suffered for four years, as i said. A woman from trinidad and a woman from ghana treated my mother like she was their own mother for four years. These people became part of our family. We still have thanksgiving with these two women. My mother passed two years ago. And the toll it takes on people it was almost like my mother had this innocence about her. She didnt understand what was going on with her body and mind. It was the people around her who were suffering. So the emphasis and dr. Barra said it, too. The recognition and focus on some of the caregivers of alzheimers patients i think is just as important as caring for the patient. When you are successful and we do develop a treatment or a cure, another one of my fears is that as we i spoke earlier about Global Health with Maternal Health and child health. Or even prenatal health, is that were not getting those things that we actually do have now here for our children to some of those developing countries. Those folks who are dont have the resources we have. And i suspect we probably have the same problem after your success in finding treatments and cures for alzheimers of getting whatever is developed to folks in less developed areas of our world. And do you see that as something that i know its first finding the treatment and cure. But once we do, getting it to folks outside of our own country, i suspect the folks in our country, for the most part, anyhow, will this will be more readily available to them than places in other parts of our world. So as we see with immunizations for children or prenatal care for a mom, my fear is that after youre successful, we might have the same problem getting the resources to the folks who need them outside of our own country. Yet you see that as an issue . I mean, two comments. I thought it was very thoughtful about your mother. And i think part of the issue in care giving is how do we train caregivers to give the quality of care that your mother got from these two women. My mother was my father was in exactly the same situation. And that quality of care and how we train people to provide this is essential. Some of this we can learn through global collaborations. On the other part of your question, can the interventions that we develop in the United States be carried abroad, we have a whole agenda at fogerty on implementation science. Taking what we have learned and implementing it in developing countries. We have learned, for instance, how to prevent mothertochild transmission of hiv. But in many countries, this has not reached all the pregnancies in mothers. And if you miss a pregnancy, youll have a child born with hiv who will need treatment for life. So in the area of implementation strategies, thats really become a priority for our research of taking what we have learned and implementing and in developing countries. I think chairman smith, one other thought since you mentioned dr. Wharf, one of the values of Global Health research from his research is that he developed methods to treat hydrocephalous without needing to revise shunts every few years in children in developing countries. Because you cant take them in for repeat surgery. So through two procedures that hes adapted, there were mixed together. One is to open the outflow of cerebral spinal fluid. The other to cauterize the coat ride plexus. He could decrease the flow, increase the outflow, decrease the input. And so he could do a single operation without the revision. That operation is now being used in the United States to treat our children with hydrocephalous. So its through that Research Done in uganda by an outstanding american neurosurgeon, seeing the need in that country to bring that Technology Home to our own children. Its another benefit of i would say reverse technology transfer. Learning from the developing world these kinds of lessons. It will make American Children survive better with hydrocephalous, as well. Since everyone mentioned a doctor and you are the only two doctors i know sboids dr. Barra, tony fauci is a friend and i remember him saying at one of our conferences that if we find if you find if youre successful in finding a cure for alzheimers, the amount of money that we gave nih in the 21st century cures act, it will pay for itself. The amount of money we spend on treating this disease. I thank you both for your work. Besides being here today, i thank you both for your work. The people who will benefit once youre successful. Thank you all. Thank you, dan. Let me just conclude and ask you, if you could, the 2017 w. H. O. Action plan. On november 13th, we know the bill and Melinda Gates foundation, now its 100 million for Alzheimers Research. The u. N. Itself has established a global dementia observatory to co late and disseminate to support evidencebased planning and strengthen policies as well as health and social care systems. Your opinion of the w. H. O. Action plan and the steps obviously, as a whole of government approach for ourselves, are you happy with it . Do you feel this is really going to be transformational . First of all, we were delighted to hear about the gates contribution to alzheimers. And i think as bill and medicli gates age, they realize this is a risk thats before them, as well. So their developmeinvestment is appreciated and shows the broadening of global interest in this endeavor. I think the fact that the u. N. Has a Global Action plan is also wonderful recognition of the importance of this problem globally. And it remains to be seen how this will be rolled out. But the fact that its there and its recognized and its recognized by so Many International partners is an awakening to the importance of the burden of this disease for all of us. Globally. Thank you. I would just support what my colleague has said. We think that this is something that needs all the best and brightest minds put towards it. And what we have observed is that as other countries are putting resources towards it, there are more and more scientists with whom we can collaborate. And thats only to the good of all. Thank you for your leadership. Thank you for being here today. If there is anything else you would like to add before we go to panel two . No, thank you. Thank you so very much. Id like to now welcome to the witness table panel our second panel, beginning with dr. Mary middleman. Who serves as Research Professor at the department of psychiatry and rehabilitative medicine Family Support program. Nyu school of medicine and the Langen Health at niy. Principle investigator of a randomized control trial of the care giver intervention funded for 20 years by the National Institutes of health. The results of which have been published widely. Dr. Middleman has expanded her Research Focus to interventions that include the person with dementia as well as the care giver. She is founder of the unforgettables, a chorus of people with dementia and Family Members, which rehearses and gives regular concerts in new york city. We then hear from dr. Richard foes, chief scientific officer for the global alzheimers platform, g. A. P. , a patient center, nonprofit organization, devoted to enhancing the speed and quality with which new treatments for alzheimers disease are developed. He retired in 2015 from eli lilly and company where he held several leadership positions for neuroscience, Early Clinical Development and leader of the global alzheimers Drug Development team. He also serves as a member of the board of governors for the alzheimers Drug Discovery foundation. A member of the board of directors of cog state limited based in melbourne, australia and Senior Associate Editor for alzheimers and dementia the journal of the Alzheimers Association. Then well hear from michael splaine, owner and principle in splaine consulting, a very big impact based in washington, d. C. Immediately prior to starting the company, he was director of State Government affairs and the Public Policy division of the Alzheimers Association leading its Grass Roots Network to priorities, including comprehensive state alzheimers plans. Wellknown as an advocacy trainer and grass roots organizer, mr. Splaine has also been faculty for Alzheimers Disease International university Public Policy, and is active at adis World Health OrganizationStrategy Group and is now advancing its policy agenda with the u. N. Based opportunities in new york and geneva. Thank you all for being here. And please, dr. Middleman, if you would begin. Is it on now . Now the time thank you. I got into this field because my mother had dementia. Im trained as a psychiatric epidemiologist. And when my mother had dementia, my family really did not cope very well. In fact, the dementia probably drove us apart rather than bringing us together. And after she died, i decided to try to figure out whether there was a way to help families like mine to cope better with the illness. And i was lucky enough to meet four women who were working at nyu, helping caregivers as volunteers. And i and i saw what they were doing, and i decided to try to write to run a Clinical Trial of what they were doing. So i wrote a grant proposal to the nih and was funded from 1987 to 2010, ultimately by the nimh and the nia to study an intervention based on what these women had been doing at nyu. The intervention, which we subsequently named the nyu care giver intervention, is a multicomponent intervention, and it is individualized to the needs of every caregiver. It starts with a comprehensive assessment of the primary caregiver and then there is an individual counseling session, the point of which is to help the caregiver to understand the needs her need or his need for support from other Family Members, friends and formal support. And then there are four Family Counseling sessions with Family Members that the caregiver nominates as important to him or her. And a final individual session. So there are six counseling sessions in a period of four months. But since alzheimers disease can last as long as 20 years in an otherwise healthy person, we thought it was important to provide ongoing support. So other parts of the intervention that provide ongoing support are a recommendation that the caregiver join a support group thats run by the Alzheimers Association or other organizations like it. And also we were available for what we named ad hoc counseling. So any caregiver or Family Member who participated in our study was able to call the counselor at any time for as long as they stayed in the study. And some caregivers actually stayed in the study for more than 18 years. So in that time, i was in the time i was funded, and because people stayed in the study for so long, i was able to demonstrate incredible benefits of this intervention, compared to the usual care that people were able to get at nyu at the time. And basically, the most important component that was not available to the control group in our original randomized control trial was the Family Counseling. So we think the Family Counseling was the key and most important ingredient in this package. In the multicomponent intervention. So what were some of the benefits that we were able to demonstrate . We were able to show that family the first thing that happened was that the primary caregiver was more satisfied with the support that he or she got from Family Members and friends. This then led to significantly reduced symptoms of depression, significantly reduced symptoms of stress. Improved caregiver physical health. And by those by those changes, all through improving Family Support for the primary caregiver, we were able to keep the person with dementia at home on average a yearandahalf longer than the people who got our usual care. So this is a really powerful intervention, and its and its power is through social support. More recently, we were able to show that this intervention could save huge costs to the health care system. In a study that we published in Health Affairs in 2014, we showed that the state of minnesota, with a population of about 5. 5 million people, could, if every caregiver got the nyu care giver intervention save 996 million in 15 years. That factoid not all the other things i told you about, depression and stress and physical health, but that fact was brought to the attention of the governor of the state of new york, who because of it allocated 75 million to Family Support programs of which now i am running one. And i think and our program is really while we would have to do what is mandated by the state, is really the core of it is improving social support for the family caregiver. And i think that everything that we have done has been about social support. And that is something which doesnt cost necessarily a lot of money. And i think in any country that could that would want to learn how to would Want Health Care providers to learn how to do this intervention, it could be done at a relatively low cost. And in developing costs often labor is cheap and pharmaceutical interventions may be very expensive. So because of our success, even before the Health Affairs article, people in other countries were interested in doing the study. We did the threecountry study in the u. S. , the uk and australia, which replicated our findings of reduced depression in caregivers, even though all of the people in the study all the patients in the study were getting deny enzil, an approved drug for dementia. We have done a study in israel that showed similar findings. And we did a study in we are currently doing a finishing a study in spanish harlem, which is showing the effects again of this intervention. So i am here to say that there is something right now that works. That it isnt a drug, and it wont cure the disease. But it can help people to live better with the disease. And i think that while were waiting for an intervention a pharmaceutical intervention, it is incumbent upon all societies to do the best they can to improve the quality of life of family caregivers and people with dementia. So some of the more recent interventions that im involved with, you mentioned the chorus, which i founded in 2011. Is a very relatively inexpensive intervention. People with dementia sing with their Family Members. They rehearse for concerts. And they give concerts. They learn new songs, which is something nobody believed could happen. So people with dementia are learning 18 new songs for every concert. Not only giving pleasure to themselves, not only finding support with other people like themselves, but giving pleasure to the community. So i think that what we can do right now is to improve social support for family caregivers and for people with dementia. Thank you. Thank you. That is so encouraging and thank you for your leadership and for providing this subcommittee with those insights. I would like to put that article, if you would we could find it and make it a part of the record. The Health Article . Yeah. Okay. I have a list of testimony of all the articles. But im happy to send it to you. Great. Well look it up and down load it and put it in. Thank you. Dr. Moes. Thank you for inviting me. Its a pleasure to follow dr. Mittelman. Most of my career has been trying to develop new medicines for alzheimers disease and i wish i could report we have been more successful. But i can tell you what we have been trying to do and give you some thoughts about how we could maybe make that happier. But medicine alone is not the answer. And so the programs that dr. Mittelman and people like her are developing are going to be an integral part of the Management Program for dementia forever, essentially. So the Global Alzheimers Platform Foundation for which i now work is a not for profit organization, founded by patient advocates. To help speed the completion of highquality Clinical Trials of potential new therapies for treating and preventing alzheimers disease. Its the belief of g. A. P. s founders, along with john dwyer, that only through rapid and rigorous testing of potential new treatments will we be able to make progress in alleviating the suffering caused by alzheimers disease. The foundation has worked with academic investigators, government agencies, pharmaceutical companies and other organizations similar to g. A. P. , outside the United States, to develop networks of Clinical Trial sites that can conduct studies quickly and with high quality. G. A. P. Has found eager partners for our efforts in the european union, where there is something called the e pad network for the european alzheimers disease network. In japan, a jpad network. Australia has an apad network and we have partnerships developing in other regions around the globe. Before joining g. A. P. , i was for 14 years, as was mentioned,atty lie lily and company, where i was responsible for clinical testing of several potential new medicines for alzheimers disease. Including two that reached large global late phase studies. Before lily, i had an academic career in new york at mt. Sinai school of medicine, where we also did smallerscale studies. Both of the come pounds at lily that reached latephase testing were very promising scientifically. They actually did address some aspects of what is called the amyloid cascade hypothesis. But neither showed sufficient efficacy to enable a registration as actual medicines for prescription. The fourphase three trials we did, usually two trials for each new potential medicine, included a total of 4,694 patients with mild to moderate alzheimers disease. And these were conducted in 31 countries simultaneously. Approximately 40 of those seen were seen at clinical sites in north america. 10 at sites in japan. 9 at sites in mexico and south america. 8 at sites in eastern europe, including russia. 7 at Asian Countries outside of japan. And 5 in south africa and australia. From these experiences with g. A. P. And lily and a lot of years trying to develop new medicines, id like to share the following observations about the global burden of disease and give you some thoughts about how i think the process of Medicine Development might be made a little better. First of all, in all the countries were g. A. P. And lily worked, we found high degree of interest. Its not difficult if you go into any of these countries to find people who are concerned about alzheimers disease. And who are eager to contribute in some way to try and develop a treatment. Its just a matter of trying to show them what it is they can do. I would say that in spite of their limited efficacy, the currently approved medicine for alzheimers disease are pretty widely used globally. We were, of course, testing our therapies as addon to standard of care. Standard of care, which in most countries did include the already approved medicines, even though they have limited efficacy. And what we found was that in north america, western europe and japan, over 920 of all the study patients we found who had a diagnosis of alzheimers disease were already receiving an a. D. Medication. But in every country where we went, it was over 70 . I dont say this is typical of everybody in that country, because theres a lot of undiagnosed people. But they are available and theyre used. It was interesting. Relative to dr. Mittelmans presentation, the primary caregivers assisting patients with a. D. As they navigated through the Clinical Trials process varied by region. Thats required, because these people have some impairment that every study participant has to have a care giver or somebody who comes with them to participate in the study. In north america, western europe, south africa, australia and japan, it was usually primary caregivers were spouses, about 70 . In all those regions. While in the other regions, eastern europe, other Asian Countries and mexico, south america, the primary caregivers were much more likely to be Adult Children or some other neighbor or person involved with the patient. Now i move on to some issues, and i think its clear from what we heard earlier from the first panel, we have learned a lot about alzheimers disease. Theres a lot of opportunities, but this is a tough nut to crack scientifically. Ive spent 40 years at it, and theres a lot of smart people out there working at it. Very hard, every day. But its proved to be hard. So id like to just give you a couple observations about how the system i think could be a little bit better. I think developing drug candidate molecules for clinical testing based on new biological findings about a. D. Could be faster. Basically, when you find some new bit of biology, the therapeutic implications are not always obvious, and it takes somebody who knows about what a medicine has to look like to make that translation. I think policies that facilitate communication and collaboration of academic scientists with those in the bio pharmaceutical industry could be helpful to enable more rapid discovery of highquality clinical candidate molecules acknowledged by the bio markers and other kinds of Technology Necessary to do clinical testing. If you just take the history of our drugs to date, the deficiency in alzheimers disease was found in 1976, the first therapy was not approved until 20 years later and that was a wellknown area of biology. What we know about abeta or amyloid, the structure of that protein was originally discovered in 1986. We still do not have a beta related therapy. Although we have tried, but its its a tough nut. I think also the conduct of Clinical Trials could be faster. Streamlining processes of study review, contracting with sites, review by ethics committees, and site certification could reduce time to completing clinical testing. Its often a bureaucratic nightmare to get these studies up and running. Granted, this is a human endeavor that well always have some human elements in it. But i think some of these are partly manmade problems. Many current Clinical Trials are designed for patients who are not yet demented, but have subtle clinical signs or bio marker evidence that they are at risk for a. D. This is a lot of the current work going on on either primary or secondary prevention. The problem is, those people are not diagnosed in the current Clinical Care environment. Weve heard that earlier. Such patients are not regularly identified in clinical practice and are very difficult to find for Clinical Trials. So if you go out to find them, the epidemiology tells me theres lots of them out there, we just cant find them readily for trials. And i think that policies that would encourage early diagnosis of atrisk patients would speed the completion of trials, as well as provide direct benefit to patients. So those are my observations. Thank you very much for your attention. Thank you so much for your testimony. And, again, for your leadership, as well. Thank you. Mr. Splaine. Good to see you. Thanks for the opportunity to appear before the subcommittee today. Lets push the button. Thank you for the opportunity to appear today. Ive been working with people with alzheimers and their families since 1986. Currently, im a consultant and since 2011, our consultancy served as the policy and advocacy adviser to Alzheimers Disease International. A. D. I. Is the global umbrella for over 90 national Alzheimers Associations, including the u. S. Alzheimers association. Of historical note, im a little bit of a historian, because ive been around. This whole panel has been around. Its worth noting, the u. S. Alzheimers association and adi share common founders. Four years after the Alzheimers Association was established by jerome stone and others, they established Alzheimers Disease International. So some sense of this being a global issue was there even in the very beginning in the early 1980s. Our current work with Alzheimers Disease International is put my associate, kate gordon and myself in the middle of a burst of International Energy and work streams that are moving on the issue of dementia and moving it closer to a Public Health priority that experts believe it needs to be. My plan with limited time is to hit the high points on what i think are Key Developments that have not been covered by other witnesses. The facts are stark, and in the introduction of the hearing, mr. Smith kindly cited the facts that i have on record, as well. One possible fact that was not cited by the chairman that might be a special interest to this subcommittee is the publication of a report on alzheimers disease in sub Saharan Africa that is less than six weeks old. That was published by adi. It estimates that there are 2. 13 million persons with dementia in that region, a number that is expected to roughly double every 20 years. Sometimes theres a belief that alzheimers cant and dementia issues cant truly be global. But with the publication of that report, and the facts therein, i think that has been put to bed. Well, let me review some key global developments. First of all, and theres a graphic in my testimony that kind of tries to demonstrate this. Dementia is increasingly understood to be a life course disease by policymakers, not merely a disease of Older Persons. Not merely a condition of complete and utter disability. Although the Public Perception that a person with alzheimers disease must necessarily be older and quite disabled in the latter stages of the disease persists. This opportunity to get diagnosed early and having early stage persons involved in the work of in many facets of the work is putting a different face on what it means to live with dementia. Even further to the left in that curve that you have in your packet is a representation of what the Lancet Commission and others have recently found. That there is action to be taken by Public Health authorities on modifiable risk factors for dementia. Keep in mind that population health, personal results may verify. Were talking about the health of the entire population. But its pretty clear, it could be summarized simply as whats good for your heart is good for your brain, is actionable today by Public Health authorities. And, in fact, there are many examples of that going on around the world. Second important second important trend or second important global development, we continue to have the detection and diagnosis as a stubborn problem everywhere. Although cited earlier, let where he just repeat what you cited earlier, which is this. Without diagnosis, there cant be treatment, care and organized support, or the opportunity to participate in research. I think some of our gap in research is the diagnostic gap. And i think this gap should also be of interest to any Health System as persons with impaired thinking and another chronic disease are expensive, because thinking is important to navigating complex Health Decisions and treatment regimens that are only frequently seen in deep crisis. Third, i want to mention in fact, already mentioned before the committee, that in the americas in 2015, paho, adopted a regional dementia action plan. And in 2017, just a few months ago, the World Health Assembly adopted a global dementia aging plan. Taking a right spaced approach, these action plans call on and will provide Technical Support for National Government plans and policies over the next five years to take advantage of our newer understandings of dementia and to plan nation by nation a response across the spectrum of the disease. I note that 30 countries have published National Plans and nearly 100 sub National Governments, states or regional governments have taken action. But i will also note that in our view, only one country has taken serious action on dementia without a Strong Civil Society push. Its almost as if we have a threelegged stool here where the advocacy, as well as the knowledge of the issues and advocacy capacity are important to move forward. On rights, another subject of great interest of this committee, let me note that persons with alzheimers disease are in some cases using the convention on rights of persons with disabilities as a platform for action on care and support. Dementia has been a special issue in the organization for american states, Regional Convention on the rights of Older Persons now out for ratification. And in a regional declaration on o Older Persons rights by the African Union. It has also been dementia and its consequences has also been a major topic in the ongoing work of the u. N. Openended working group on the rights of Older Persons. Last and ill leave the rest to my written testimony, a Broader Community of interest in dementia as a social issue is emerging. Its taking many forms, such as the organizing of nearly 20,000 Young Professionals in indonesia around the issue of alzheimers who dont have family experience, as well as issues being an agenda item at the World Economic forum in davos or this week at the sals berg global seminar. Also in the wake of the japanese tsunamis we saw for the first time, disaster authorities paying attention to the problem of alzheimers disease. Multiple International Organizations help raise awareness during alzheimers awareness month. And even pope francis made a major address on world alzheimers day last fall. Its fair to mention that myriad Scientific Meetings in cooperation are increasingly becoming the norm. The Worlds LargestScientific Meeting on alzheimers disease is hosted and will be hosted in our country by the Alzheimers Association in chicago in july. It will be followed this year immediately by the annual conference of Alzheimers Disease International. Truly a global gathering. As i was preparing this testimony, my last thought is faces come to mind. Faces of families such as my sisters, my aunt lee, my aunt marilyn, my mother in law. Also faces of people like lucian and dy and even two women from yemen who started this moment i i have to think about researchers in poland and the Czech Republic all over eastern europe. Theyre truly is a global theres a global view in my head. I also cant not mention that im here today principally because 13 that have years ago my brother gave me a kidney, so thank you again, dan. Im tondone. Thank you to your brother. Your leaders, you have made all the difference in the world and i think your point, mrs. Plane about the importance of advocacy when people have a message that is well founded and they back it up with empirical data, it gets action on capitol hill, as dysfunctional as people think congress is these days, we are getting important things done. A tripling of the funding for alzheimers and i do believe well get to there with the appropriations bill is no small achievement. I introduced the Ronald Reagan break throuthrough act for year working alongside of you and others and we couldnt get even a markup and now were at the point where the monies actually flowing and were talking about a tripling, i should underscore a tripling since 2015 so that burst that you talked about needs to become a sustain bible surge for the sake of the patients, the families, the caregivers so thank you for your advocacy, all three of you and others who have been instrumental. We dont focus enough on how Health Systems could implode over the next 30 years or so. Caregivers deflect a lot of those costs that would be born and, doctor, you know better than anyone. So often its the spouse or daughter or daughterinlaw that steps up to the plate to take air of the alzheimers patient and your work i hope, maybe you would with answer this, whether or not the w. H. O. Knew the agenda item, the surge that theyre making, the new seven point which includes in its seven points, you know where is it providing support for care makers of those living with dementia, caregivers, its one of their seven points. Hopefully theyre listening to you in the breakthrough landmark work youve done so they dont have to reinvent the wheel. Can you put on your mike too . I neglected to mention earlier that because we were so successful in these randomized control trials of which there has been more than one, we and we were being asked to provide training for providers mostly social workers but also people in allied professions and we were going all around the world to provide this training as far as israel, france, australia, sometimes it was fun but eventually it got to be too much so we got we got a grant from the nih to develop online training. So now people can receive training in how to provide the intervention online when they wish only in english and in australia at the moment but american english and australian but one could easily imagine how this training, which includes videos of both role plays and real cases of family caregivers being given the counseling could be incredibly valuable even if people didnt do the actual nyu caregiver invention as we developed it to have the training and to understand how to work with families to help them to support the primary caregiver. How hard is it to access that . Could you give the web address . At the moment it has a cost because its developed with an sbir grant, but it is available and id be delighted to talk to you about more online or offline. But in addition to that, we encountered another issue that he thought was worth developing a solution for, which is that very often families are dis pursed and there could be a primary caregiver in miami, florida and the daughter in new york and the daughter cant participate couldnt participate in personal counseling or and felt left out of the care. So we developed video a Video Conferencing version of our intervention which were doing a randomized control trial of right now. But i think of that as a potential for people who live who have Family Members that live in other countries, perhaps the adult child is living in new york and the parents are living in china, wherever, one could use Video Conferencing potentially in countries where and for people who have access to the internet to bring Families Together and to provide them them and the primary caregiver with the kind of support that they need. Is w. H. O. Accessing this not that i know of. I know a little bit about that work. I think theyre not just looking at made in america programs. I mean they are the Global Health organization and there are many to the level that we accept in the United States random Clinical Trial, peer review journal, evidence based programs that were not invented in the United States. So i think the task of the very small staff working on dementia at the World Health Organization. Did i say that clearly enough . How small . Four, six. A place where where the United States government could frankly make a real difference with a couple of key people from the United States to either pothole or to w. H. O. , which is minuscule dollars compared to what kind of rich resources we have could make a huge difference, but they are compiling an evaluating and not reinventing the wheel but the wheel goes both ways. One of the things we get asked all the time by a. D. I. As representing a. D. I. Is, can you help us access evidence based portuguese language, Spanish Language programs that chinese language programs that were invented and validated in other cultures because thats what were dealing with as america ages and changes demographically. So i think, you know, its bidirectional, its multidirectional. I also think that you mentioned Health Systems. Let me just say, the population aging is global and its really an opportunity for from a n noncommunable disease as well as an aging group, in Global Health. And take start to factor in not just the disease by disease approach but really maybe this whole theme of noncommune cabca diseases going back to my testimony about the linkages between brain health and other health. It might be an opportunity for the committee. Great idea. Thank you. Please take a look again at our global rain Initiative Bill because Infectious Diseases are horrifyingly prevalent in africa but with bushs program which is about 5 million a year, arvs, the pandemic, its not over but its been mitigated and other malaria, all those diseases are being attacked as they should be but we leave out brain Health Except for the diplomacy at w. H. O. And elsewhere. Let me ask you you mentioned the africaen countries, 2. 1 million, has the au, African Union been responsively at all . The African Union is one of only two regions in the world that has an explicit rights policy for Older Persons and alzheimers has been part of that story because unfortunately, in some pockets in africa, people with alzheimers disease are perce e perceived as witches, demonic and literally have disrupted these witch camps that were developed as a way of stashing people clearly disabled from severe cognitive issues from alzheimers disease or dementia. Theres some visibility. Theyve got a lot on their plate but i think population aging is becoming better known. There have been two regional meetings inside of a year of people interested in doing more about alzheimers disease on the african continent that have included African Union representatives. Theres also country by country but also as a region, i hesitate to say but i think its one of the most active regions in organizing around nonkpun cabca diseases and other interested parties, because thats becoming part of the reality of help in the region as well. Let me ask, do you believe that we are on track to by 2025 to get a disease modifying treatment or maybe even a cure or other countries like japan and china, the uk, coming forward with sufficient monies to particular on the Research Side to have that Critical MassManhattan Project type of focus . There is no doubt that in the country that have a large number of older people, particularly japan and china and western europe, youll find a lot of money being devoted to Alzheimers Research. So i dont think that that is the issue. I think theres a certain amount of discouragement that comes with lack of more tangible success, but it would help if we have these existing International Organizations like w. H. O. And o. E. C. D. And so forth actually make this a priority because it gives some credibility to these National Organizations that are trying to do something about this to go ahead with International Cooperation and the perception that this is really a high priority globally. Can i make a comment . Yes, please. I think that when we are trying to find people to participate in Clinical Trials of new drugs, if we have psycho social interventions as well as we did in the three country study, these trials may seem more attractive to participants. I think thats white true and its interesting that for a brain disease to not more fully recognize the interplay between psychosocial and medical interventions is a little odd. Its hard for me to imagine in cardiology that they would think that medicine without exercise and weight control is going to solve the problem, but we just have to get an understanding that all these things have to Work Together and i think from a patient acceptability standpoint, the psychosocial interventions are much more tangible and immediate and provide a more immediate benefit for people who participate in these trials. And the final question, i do have others that i would like to submit to you, the issue of brain imaging that we discussed with panel number one, do you see that as a viable diagnostic tool Going Forward particularly for early on set . We were involved in some of the early developments of those technologies when i was back in the pharmaceutical industry and i think it has assisted a lot in getting more biologically uniformed people entering into Clinical Trials. Its role that ordinary clinical practice in the absence of directly related therapies is much more limited but theres been discussions by that. Its clearly a great advance to have a brain disease where you can actually see the pathology in life. Thats something weve almost never had for any brain disease in the past. Mr. Garret . Thank you chairman, smith. I was in another committee and got here as quickly as i could. I did not imagine that i would have the opportunity in the Foreign Affairs committee to discuss alzheimers and so im delighted that that opportunity has presented itself and i thank the chairman again. Now having said that, i will tell you that you probably didnt imagine the direction that im about to go here. I think its fair to say that a rising tide lifts all ships and i would ask rhetorically because i dont want to waste your time whether or not we do medical Research Well here in the United States. I think the answer is yes, relative to the world we do a pretty good job, right. The next rhetorical question would be, with the designation of a particular item as a schedule one controlled substance stymied the ability of entities whether government or private to research said schedule one controlled substance as it related to medical uses and i think the answer if anybody disagrees with me youre welcome to chime in. You can interrupt, but i think the answer has to be yes and so obviously some of you are probably miles ahead of me because im a lawyer not a doctor but as i look through a list of medications derived from plants i find medications that help with Blood Pressure, with malaria, with pain, with antitumor agents, sedatives, muscle relaxants, inhibitors, when you look up medical plants youll find a list that is literally in the hundreds. The question that i have for members of the panel is, and im not arguing in favor of any pan seeia or any over arching wonderful solution but what we be well serve today review our scheduling of kanaboids to allow the research to be done because as i look for studies that relate to cgd oil and alzheimers specifically, i find a lot of them and they all come from the netherlands, australia and Great Britain and weve tied our own hands behind our back with an archaic legal structure that denies the opportunity to find potential cures or at least aiding elements by virtue of the stigmaitation of a particular plant. Could we further potentially Better Outcomes and at least addressing symptoms if we were to free the circumstances that currently stymie the private sector and even public monies from being used to research ca nab anoise . I dont know that i can give you a complete answer to that question. Couple of comments, though. Your quite correct that many current medicines are were originally discovered as extracts from the natural world, from plants or someplace else and thats been the case throughout the history of the development of medicines. My own view and i just speak from a couple of companies that ive worked with, yeah, it would be a certainly a consideration if if you were talking about trying to develop a scheduled substance as a new medicine that means you got to do other studies, abuse liability and potential harm, you know, we used to have a saying, no side effect, no drug. So usually medicines have some unwanted effects along with the desired effects and the important part about any Medicine Development program is that you fully understand both of those so that in the end if the judgment is that the benefits outweigh the risk that treat that can be approved with an appropriate labelling of all the benefits and the risks and its the nature of the developing program that it should investigate both of those things but if your point is that it would be a weighed negatively on a company thinking about developing something where you had this whole other side path trying to mitigate the risk, i think the answer is probably yes. Theres an inherent cost sure. Theres a cost, more studies, more time, more potential. You dont want to start out with a potential new medicine where you know right off the bat that its got down sides . Theres no arguing certainly that there are down sides. If im correct, that hemp extracted you dont get high. Its not even a side effect as its administered therapeutically, right . I think there are canabonoid derivatives that make you high. I open the floor to either of you fine folks to comment on whether it might be easier or more costeffective to study potential positives if the scheduling regime in the United States were relaxed to allow more efficient and cheaper and more ready studying. I actually think that one of the benefits of psychosocial interventions is they have absolutely no negative side effects. I would go in the other direction. If i were try to do things that were unusual i would try to figure out what nonfarm logical interventions could have major impact. For example, nobody believed when i started that people with dementia could learn new songs and they are learning new songs. This is a medicine that has no potential side effects. In fact, we did a video and one of the caregivers said forget about pills, just give me this. Now imagine if singing could have a major impact on neurological function and we dont think about those kinds of interventions. I think what youre saying is brilliant and i appreciate it. Im an all of the above kind of guy and what might work well for one individual or entity might not work as well for another but what youre doing is commendable and i admire you. I simply submit that because one thing works doesnt mean another doesnt and i believe we have a regulatory scheme here thats draconian at best. I agree with with you on that but i think what youre talking about is thinking out of the box. Yes, maam. Were not arguing, were agreeing. Yeah. Mr. Splain. Im not a doctor, dont play one on television. A couple of thoughts. I wonder whether is it schedule one or are there other things that prevent this kind of imaginative thinking about experimenting with these substances. So couple of thoughts on that. One is, we do have pretty strong not invented here ethoughs in the Scientific Community and i think thats made more challenged because there is a prevailing theory of alzheimers disease in the United States and in the United States science establishment that, although respected in other countries, theyre investigating along different lines. For example, mr. Smith, i dont want to correct you except i will. I would add the republic of korea to your list of very engaged countries about alzheimers also from a Research Point of view. Their drug mechanisms of action, remember alzheimers has three parts, it has plaques, tangled and inflammation. Theyre almost completely zeroed in on inflammation and its something thats its not ignored but its not a mainstream in the United States. I think thats just its just something to think about is the prevailing theory keeping this out of consideration rather than schedule one. Last, our language about alzheimers treatment is most unfortunate in that some where in the 1980s we started talking about disease modifying drugs and mere symptomatic treatments and we have minimized social interventions, we have minimized the drugs we have by calling them mere symptomatic treatments. I would submit, what is insulin . A mere symptomatic treatment . Yes, but it also what do people want when they live with a disease . I can tell you first hand as somebody who has lived with disease, we want treatments that allow us to get on with our lives. So i think sometimes the language and holding out for this is why i get really uncomfortable about will we have a cure by 2025. We have this language weve developed in alzheimers about symptomatic treatment versus disease modifying treatment and i think that too is a barrier to people thinking outside the box. So its those other things that are going on in the alzheimers scientific thinking, not so much that its a schedule one problem. Well, let me indulgence of the chair very quickly submit that while we search for a cure in the interim we should also be searching for treatments, right . Its an all of the above not a one or the other, and so while we hope one day to move away from fossil fuels, in the interim were burning oil as we develop wind and solar. Let me ask you this and im leading intentionally because i can here, would you not agree that schedule one designation inhibits research and makes that more tedious and costly for those who might be interested in engaging in it . I was actually addressing that i have never had any clinical candidate that i was responsible for impeded in its development by scheduling. That doesnt mean somebody else might have and honestly, in my time in the pharmaceutical industry, most of our interactions with fda were actually quite helpful. They were leading forward. There may be some areas that i didnt get into where theres some adjustments that need to be made but i will tell you they were actually quite forward thinking in their treatment about approval processes for alzheimers disease. I think they knew quite well that it was a very bad disease and were willing to work with any sponsor that came to them with any reasonable proposal about how to develop a treatment. But if you want to work with willow bark you dont need to get federal government permission to get the precursor . Any way. Thank you for being here. Im not suggesting this is a panacea just that we should get out of our own way and thank you all tor thinking outside the proverbial box. I think its an all of the above and open mind and look at what works and what doesnt. Thank you, mr. Chairman. Ill conclude. Any comments or questions that went unasked, please if you could provide those answers. The idea of a goal that we developed with a bill and also the g7 isnt that its its to sharpen the mind as you know. Thats why ive asked are we on the right path to either achieve it or come close and even coming close will be an achievement. I do dr. Mohs, you make the point to develop truly effective ways to treat and delay on sets will require many studies, patient assistant technologies and common approaches. We are doing that, right, or are we lagging in any of those areas . We are doing it. I think it could be done a little faster. The scientific uncertainty is still great and so the only way to tackle that is to accumulate knowledge as fast as you can and that requires how many compounds are being tested i think the last we checked there were about 30 something in phase three and in the 60 range in phase two and usually companies dont report earlier than that because its so iffy its hardly worth reporting. Theres a lot. And that doesnt even take into account all the little labs and so forth around the world, but on problems like this you need a lot of ideas, you need a lot of studies to help resolve the uncertainty about those ideas and the communication from different laboratories to each other so they dont repeat and followup on unpromising areas is very important. I want to thank you again for your leadership, for being here today. And i thank you again. Hearings adjourned. Youre right. I didnt see that coming. [ no audio ] [ proceedings adjourned ] [ no audio ] [ proceedings adjourned ] [ no audio ] join us on cspan3 this weekend for American History tv. Saturday at 3 00 p. M. Eastern, in honor of the 50th anniversary of the 1967 public broadcasting act the library of congress hosts a discussion about the history of news and Public Affairs programming with former pbs jim lowerer and talk show host dick kafat. And how churches help members gain experience with organizing and running for political office. Sunday at 8 00 a. M. Eastern, recollections of the battle of midway from four World War Ii Navy veterans and sunday on real america, the film dreams of equality featuring a recreation of the 1848 womens right conventions. American history tv. All weekend, every weekend. Only on cspan3. And now a portion of todays washington journal focusing on the possibility of a Government Shutdown on december 8th and the republican tax reform plan. Always glad to welcome Oklahoma Republican tom cole to the desk. Veteran of many previous fiscal shutdown fights on capitol hill. Whats your sense of this latest