Lessons in Lifespan Health

Kate Wilber is the Mary Pickford Chair in Gerontology and director of the Secure Old Age Lab at the USC Leonard Davis School. She's also the co-director of the National Center on Elder Abuse, which is housed at the Keck School of Medicine of USC. She recently spoke to George Shannon about her research, including her work exploring ways to provide long-term care services and supports that allow older adults to be as independent as possible and the challenges and opportunities that technology provides in this area. Quotes from this episode On building on lessons learned during the pandemic "I think a lot of what we saw were challenges that we already knew were there - how fragmented services are, how older adults can be at risk of isolation, how important the home community-based services and programs and opportunities to interact are for everybody. And I think showing the importance of community, which we didn't have during the pandemic, except a bit on social media and phone calls and maybe people getting together outside. So the key question is, how do we take the learning and the recognition of what we already knew into the future to build on these important lessons, to do better with our aging service delivery? I was going to say our aging service delivery system, but that's a huge problem. There isn't a system; there's just a lot of different components of a system." On innovations in long-term care and supports "We have to prepare for an aging population. And until recently I felt like we didn't do that great a job preparing, but I see a lot of exciting innovations, which to some extent may have been jump-started a little bit because of the challenges of the pandemic. We have a variety of models of senior living and I think we're going to see more innovation there or the innovations that have been developed take off because they did better in the pandemic too. So if we look at what kind of care was best for older adults who maybe were isolated or need long term services and supports during the pandemic, how do we build on that? And how do we make sure that we translate what we know into reasonable programs and policies." On barriers to implementing technology solutions "People not only need to have some kind of device. They need to have broadband, it needs to work. And we've seen that in some parts of the country, especially in rural areas, broadband it's not available. All the things we take for granted, electricity, water, et cetera, how much is this an essential service that we'll do a better job providing across the nation in areas where it doesn't exist very effectively now. And then as I said, how do we help people learn? And what are the particular cultural competencies required for trainers? What are the different uses that people want? This gets back to being person-centered and engaging the people that will be the end-user users and understanding what's most effective for them. There are still a fairly large proportion of older adults who don't have access to any sort of computer; some have smartphones. And there is this notion, I guess, if we build it, they will come. Or if we give it to them, they'll use it, it would be the way of talking about that. But there's a variety of barriers. And if you hand somebody a box with a computer in it and say, 'There you go, you're now going to go on the other side, the right side of the digital divide.' They're not. So what can we learn about how to help people use technology in a way that is useful for them effective, meaningful?" On telehealth "So this will be a time saver. I think that's pretty clear, but the nursing facilities have to invest in it. The staff have to invest in it. They have to learn how to do it. And one of the things we're seeing is they thought the residents would be the most resistant and they're not. They're like, 'Okay, if I can see my doctor this way, fine.' But I think the question is, how is it used, where is it most effective and where is it not a good replacement for a physician coming to the facility? So, there's a fair amount of literature developing on this, but I think there's so many exciting innovations that are rolling out and we need to build on what we're learning and make them better and be more effective in the next generation of telehealth and facilities and helping people on the digital divide connect. So all these things are really exciting opportunities to learn how to connect." On person-centered care "So the idea behind person-centered care is that people have different needs. Of course, they also have different preferences, different preferences for care and for services and for supports and for contributing and giving back and primarily and mostly as with all of us, for controlling their lives and the decisions that are made. So person-centered care recognizes that the power should live with the individual in terms of the ability to make decisions about care informed decisions. But I think sometimes, we, as professionals can see, oh, this would be best for this person. And professionals are extremely busy also. And so it kind of overlooks sometimes the person's needs and preferences and working in areas like elder mistreatment and elder self-neglect. A lot of times people have legitimate reasons for wanting things that we don't necessarily think would be the best choice, but person-centered care asks us to really get in touch with what's behind those preferences. And to what extent can we ethically honor them and this is something I see the field doing a much better job thinking about and working on and great things have been written. And the American Geriatric Society a few years ago had an expert panel come together and develop a definition and sort of protocols for this. And I think that's really moving the field. One more thing I'll say is that ageism contributes here. So we make assumptions about older people that they can't express their preferences adequately. And providers talk to the caregiver, not the older person. Or they say this is what needs to be done. So I think there's also a culture change of recognizing that it's about the older person. And we start with the older person, and that's not to say that there aren't age-related increased likelihoods, but not inevitabilities of memory issues and things of that kind. And so we need to be clear that the person has the capacity to express their preferences, but we start with person-centered. The elder is the person who whatever is happening is happening on behalf of, or for, or with. And that's where we start." On students "That's our future. … Our legacy is you see the students that go through our program and they're very excited about learning and they bring innovation and enthusiasm, and then they go out and do wonderful things and they become the leaders of the field. And you could see that across the board in so many areas."

Rong Lu is an associate professor of stem cell biology and regenerative medicine, biomedical engineering, medicine, and gerontology at USC. She joins George Shannon to discuss her research into the complex and surprising behavior of individual blood stem cells and what it could mean for treating diseases associated with aging. Quotes from this episode On stem cells and what makes them so promising for medical research Stem cells are the special cells in the body that can produce other type of cells. So in particular there are two type of stem cells, one called embryonic stem cells that only exist in the embryonic stages. And the other type of stem cells are called somatic stem cells that are also exist in adulthood. And these somatic stem cells can produce only a specific subset of the cell types in the body. For example, skin stem cells can only produce skin cells and blood stem cells can only produce blood and immune cells. But all the stem cells share the general special property called self-renewal and differentiation. So differentiation describes their ability to produce a different type of cells and self-renewal refers to their ability of making more of themselves over time and sustain the long-term differentiation and tissue regeneration. On the ability of stem cells to regenerate as we age …that's what makes stem cells super special because they are the only long-lasting cells in the body that continuously regenerate and sustain the tissue. But over time, stem cells capacity in terms of self-renewal are reducing and therefore the tissue as homeostasis decline when the body ages. On whether stem cells might offer protection against age-related immune decline Sure. So over aging stem cells become less and less competent in producing immune cells. And, the hope is if we can maintain the stem cells capacity over time then we could make the stem cells offer the protection. Again, this is very much a research in progress and many research labs are working on this important question, including my own lab. On the focus of research in her lab In our lab, we're interested in understanding how are individual stem cells different from each other and how different stem cells work together to maintain an overall balanced blood pool. And in particular, over aging, we want to understand how individual blood stem cells change during aging and how their change lead to the aging phenotype of the animal. And what we found is that there are a specific subset of blood stem cells that age, particularly faster than the others. And there's also another group of stem cells that actually can change in the opposite way during aging and provide more immune cells and their presence really correlate with the delayed aging phenotype of the animal. So we're very excited about this finding and we're following up on this study using our bar coding tool to track these anti-aging stem cells and study what make them so special. On the development and use of a tool to label individual cells with unique "barcodes" The barcoding tool was developed a couple of decades ago by several labs simultaneously. At that time they used the viral insertion site as a marker to track individual cells. So about 10 to 20 years ago, high throughput sequencing technology started to emerge. And at that time, I started to combine the new capacity of this high throughput sequencing to quantify the cellular behavior at a single cell level. So instead of using viral insertion site, I provide a particular DNA barcode sequence into the virus and use that as a marker to track individual cells. And what this allow us is a high precise quantification of the cellular behavior and also the high throughput that is needed to track hundreds and thousands of stem cells in the body. We can use this tool to study cancer cells and understand the heterogeneity among individual cancer cells. For example, a recent study from my group used it to track the primary acute lymphoblastic leukemia cells in xenograph mouse model. And what we found is that individual leukemia cells have different ability to grow to metastasize and to respond to the drug treatment. And we found that some cancer stem cells that are particularly resistant to drugs to drug treatment In particular, some leukemia cells that are particular resistant to chemotherapy treatment, exhibit distinct gene expression signature compared to others. On gene expression signatures The gene expression signature means these particular subset of cells express a distinct subset of genes that make them different and potentially may cause their specific drug response behavior. So these particular gene expression signature can allow us first to identify these cells and to detect whether these cells exists and whether the patient has the potential of resist chemotherapy. And secondly, these gene expression signature can also be potential drug treatment targets to allow us to particularly target these cancer or leukemia cells in the therapeutic treatment. On future directions in aging research So in the context of aging, we are very excited about our recent discovery of these anti-aging, uh, stem cells. And we would like to further understand how to activate these anti-aging behavior and how to expand their function in the animal. And we are also very excited about our discovery on the cellular heterogeneity in disease, in particular, in their response to chemo drug treatment. And we would like to further identify the potential functions of the gene expression signature that we discovered. In addition, we also want to understand whether the microenvironment of the stem cell play a role in terms of instructing their heterogeneous behavior.

Assistant Professor of Gerontology Ryo Sanabria joins Professor George Shannon to discuss their research seeking to understand why stress response pathways break down as we grow older and whether there may be ways to delay that breakdown and potentially promote healthier lifespans. Quotes from this episode On the definition of stress: Stress can come in so many different forms and flavors. It can come in the form of something external, something like heat stress. For example, being out in the desert heat, it can be something as similar to cold stress of a winter storm, or even something like a bacterial or viral infection… Stress can also be internal though. It's not only external. When we think of humans, we can think of big things like mental stress, emotional stress, social and societal stressors. So really the definition of stress is pretty large. And just to say anything that causes some kind of adverse reaction to the body is a stress. And so we study all of these various types of stresses and how it impacts our bodies, our health, and of course aging. On how our cells respond to stress: The response to stress within the cell is simply to activate mechanisms that prevent damage. And the main way that this happens is to turn on genes. So genes encode specific types of proteins and processes and mechanisms that are important to mitigate the stress. So it's like essentially activating or turning on a switch that has some kind of functional output, similar to how you will just flip a switch to turn on a fan or an air conditioner. So you can cool down the house. Exactly in the same way, the cells will switch on jeans that can activate pathways that prevent or mitigate that is associated with exposure to stress. So for example, when we are under heat stress, our cells will turn on the mechanisms and pathways that will essentially alleviate damage associated with heat stress, such as damaging proteins or things like that, that happen under heat stress. So the cell is essentially trying to repair or discard damaged proteins that happen with exposure to heat. On efforts to give older person to have a younger person's ability to deal with stress We know that the capacity to deal with stress declines during the aging process. So the question is if we give an older person, a younger person's capacity to deal with stress, would that actually combat aging? So if we go back to example again, before, if I give the grandmother her grandchild's capacity to deal with desert heat, we know that she'll be more resilient to the heat. She'll likely survive the desert, but generally, would she actually be healthier overall as well? Would she be in a sense younger? And the answer in most model organisms that we study is yes. When we give an old organism, a young organism's capacity to deal with stress, not only can they handle that specific stress better, but overall they're healthier and live longer. So when we think about model organisms, what we're doing is activating those genes that I talked about. So essentially turning on those switches that will then activate a specific pathway, like in the example I gave earlier where heat stress causes damaged proteins, you can turn on the switches that will essentially activate pathways that will remove or repair the damaged proteins. So what happens during the aging process is that the capacity to turn on these genes switch on these genes are impaired. So what do we do with this? We really try to increase the capacity of that gene to turn on. So it would be like increasing the electrical circuit's capacity to pump energy into your AC so we can increase the gene's output and in model organisms, this is easy. We can simply overexpress your gene. So what does that mean? If we think about the number of copies a gene has, usually one gene will have one copy, but if we give an organism 50 copies of the same gene, even if we decrease the output by half during aging, you're still having 25 times the gene expression, which will improve the overall outcome. But of course, in humans, you can't just go in and increase the number of copies of a gene. We're not yet there for gene therapy. So what can we do in humans? Well, if we know what specific mechanisms are activated by the gene, we can try to target them with drugs. So use drugs that increase the function of one specific mechanism. So we know many of the genes and mechanisms that get activated when we're exposed to for example, heat stress. So we can try to develop drugs that activate these pathways to essentially hyper-activate the stress response and try to use this to combat aging. On the concept of hormesis and the benefits of exercise: Hormesis - what it means is that exposure to low levels of stress can activate a beneficial stress response that makes you more resilient to exposure to future stressors. Exercise is exactly this. When you exercise you're stressing out the body, you can get micro-tears and the muscles when you do strength training, and that's what lets the muscles grow and become stronger. Any kind of cardio or any type of fitness will make your body temperature elevate, which will cause a mild heat, stress and exposure to all of these mini stressors during exercise activates all of these stress response pathways that I talked about before. And so when your body faces stress, you essentially become more resilient to it. So athletes tend to be healthier mostly because they have a higher tolerance for stress. Their bodies are better able to mitigate damage associated with stress because their bodies can activate stronger stress responses. So the concept of hormesis is that what doesn't kill you makes you stronger. Every hardship you face makes you more resilient and stronger to face the next one. So truly there's a connection to exercise and fitness as a model of essentially adapting to stress, to essentially combat aging. On the benefits of stress Yeah, I know we covered a lot today. I went into so many diverse topics, so I just want to summarize everything by, uh, saying Kelly Clarkson sings it right. For sure. She says what doesn't kill you makes you stronger. Definitely true. So while people will always tell you avoid stress, it isn't good for you. I want to just say, well, some stress isn't so bad living a completely stress-free life might actually not be so beneficial. So let yourself experience some good stress, work out, go to the gym, fight off a bully, maybe, immerse yourself in a challenging job. Everything you face in life will make you that much stronger. And who knows. It might even positively impact your lifespan.

Research Assistant Professor Thalida Em Arpawong joins Professor George Shannon to discuss her research to better understand how our genes and environments influence how we respond to stress and adversity and impact how we age. On the definition of bioinformatics and its use in research "Bioinformatics is a science subfield, but really just refers to a set of tools that we use to collect, analyze, and interpret findings from large volumes of biological data. We use tools like super computers, biostatistical models, computer programming, and specific types of software, while at the same time, integrating biological concepts to guide how we use these tools. So the data we use—we call it "omics" data, for short—includes primarily genomics, transcriptomics, epigenomics, proteomics, metabolomics, that is, all the omics. Here in the school of gerontology, Dean Cohen had a vision of creating a core to help support researchers in their labs that want to use omics data but may not have the background to do so. So, relatedly, with the Genomic Translation Core, we also use bioinformatics to work with human data, to collaborate with biologists. So these biologists work on model organisms for their research, like worms, mice, or yeast, and the biologists who have been granted pilot awards through the Nathan Shock Center because they've made some important discoveries in their model organisms, we work with them to confirm what the relevance is of their findings for human aging processes. It's an exciting time because through this work together, we have the potential to use the expertise across different disciplines to answer some bigger questions that we haven't been able to previously with regard to cross-species effects of genomics and health." On her research on how experiences of stress and adversity throughout different developmental stages in life and genetic factors work together to influence emotional and cognitive health as we age "So we used to think that genetics was much more deterministic, but we now know there are much more complex and interrelated processes occurring. We found that social structures in which we can characterize groups, such as gender, race and ethnicity or social status, are very importantly related to how genes get expressed. Similarly, people's behaviors shape levels of gene regulation and expression, then have downstream effects on immune system health, development of chronic diseases—for example, obesity, heart disease, depression—and even lifespan. So it's becoming more critical to include these key social factors in human research when we evaluate the effects of genomic data on health." On her research looking at how having early childhood adversity and adulthood adversities affect the level of depressive symptoms when older "What we found were two main things. First, that there was essentially a dosage effect, so that with each additional childhood adversity, there was an even greater risk for more later-life depressive symptoms, even after the age of 50. And second, the hypothesis that was supported was called stress proliferation, which is essentially the idea that stress begets stress. So therefore, earlier-life adversities are accompanied by more adulthood adversities, and that's how they work together to impact mental health later on." On the mind-body connection, or the role of mental health in healthy aging "When we think of psychological factors, such as stress and adversity and socioeconomic hardships, compared to other factors that affect aging, we're finding that there are more influential compared to genetic or biological factors. And in a recent study by Eileen Crimmins, she found that, in particular with mortality and cognitive functioning, these factors explain 25 to 30% of the variance. So that's a significant amount and often much more variance explained than we can detect for something like genetics." On epigenetics and how our social environment can affect our genetic expression "We used to work under the assumption that the effect of genes was best studied at the level of a genotype or just what's encoded in our DNA sequences. But we're finding that there's so much more and we need to measure how our DNA has structural changes that occur throughout life that are not in the code itself but actually in our epigenome. So similar to using genetic risk scores, we can actually now calculate these epigenetic risk scores, and those tend to encapsulate things we've been exposed to or behaviors. … There is research on how we react to stressful experiences, how that it gets embedded into our epigenome. And we can quantify some of that using these epigenetic scores." On the role of education in health outcomes as we age "Education is important for aging because it's one of the most consistent measures to relate to almost all of the health outcomes that we look at, including cognitive, emotional, physical outcomes, financial outcomes, and mortality. So it's an important aspect, and what we found is that the heritability of educational attainment has been estimated to be around 40%, which then leaves 60% attributable to social influences, or the environment, but unpacking how those genetic factors and environmental factors sort of work together is important if we're looking from the perspective of how to promote more education, especially for those at high risk for some of the negative health outcomes." On her research looking at psychological resilience in aging "I appreciate that the aging field is really the only one that embraces the resilience concept in a way that there isn't a sole focus on disease or deficits, but an interest on healthier aging or successful aging from the perspective that there are different processes involved than when avoiding or preventing disease and morbidity. A lot of my work has focused on psychological resilience in different developmental stages of life, which means evaluating what contributes to people doing better than expected in the face of adversity or challenge. So not just having greater wellbeing or greater health, but having those states despite having been exposed to having to adapt to life insults and significant stress. So what I'm focusing on now is evaluating lifelong effects from adolescents through older adulthood for psychological resilience and how that affects biological aging." On her research looking at the importance of physical activity across the lifespan "One of my projects uses the Project Talent Twin and Sibling study to answer the question of 'Does it matter when somebody is more physically active in earlier life or later life, or do you need both to result in better cognitive and emotional health later on?' and how much of the determination of those behaviors is nature versus nurture. For instance, how much is physical activity dictated by socioeconomic adversity when growing up or [by] later-life financial constraints? And then with regard to nature, one key finding is that there seems to be very little overlap between earlier and later life physical activities that's due to genetic factors. So I didn't expect to find this, but it's interesting because from a public health perspective, I'm interested in how physical activity is a protective factor against adversity [and] results in better health and how the implications for findings from this work can inform how we design interventions to support how individuals adapt to stress throughout life." On the concepts of generativity and post-traumatic growth "There has been a lot of research on generativity and how that relates to a resilience concept called post-traumatic growth. So people who've been through really intense, kind of acute stressful experiences have to reflect and rethink what their life means, what their purpose is, what their direction is in life, how they orient to people and relationships. And one of the things that is very related to gaining more post-traumatic growth is, for older individuals, having this perception of greater generativity because I think there's that relationship to purpose and meaning. And at the same time when you're talking about looking forward, there's that whole concept of future orientation that also is related to higher levels of post-traumatic growth and adaptation post-acute stress and adversity. So I think these are all very intertwined and interesting." On efforts to study the effects of mindfulness and meditation "There's that whole field of psychoneuroimmunology that also bears some similar concepts [to transcendence] where there's a lot of researchers who were looking at things like mindfulness, or flow. But the concept of mindfulness, I think, relates to transcendence and there is a whole group of researchers that formed these collaborations with the Dalai Lama, and they were trying to conceptualize how to operationalize these aspects of meditation and other things that we find are beneficial, but we can't really study that clearly. And so there is a whole area that has emerged about the mind and the psyche and how we can use the mind and psyche to manipulate the effects on our immune systems and other aspects of our biology." On expressing gratitude to research study participants "I'd really like to thank all the people who participate in surveys. Some who've taken part since high school, in the case of the Project Talent Studies, and allowed us to follow them up over 50 years later, and others who've answered question every two years for almost 30 years, some have given DNA and biological samples. But this method of tracking people's experiences, their natural histories, their biology, and how well these all come together has been absolutely invaluable to research across so many fields. And what we know about life course risk and protective factors for health as we age would not be where it is today without these folks, especially the diverse range of folks involved, so we can make research more relevant to addressing health needs for everyone. So if any of them are listening, a hearty, very grateful, 'Thank you.'"

Mireille Jacobson is an associate professor in the USC Leonard Davis School and the co-director of the Aging and Cognition Initiative at the USC Schaeffer Center for Health Policy and Economics, where she's also a senior fellow. She joins Professor George Shannon to discuss her research using economic insights to better understand decision-making around vaccines, palliative care, Alzheimer's disease and more. On health economics and the role it plays in healthy aging "Health economics really is just the application of economics to health and healthcare… So whether it's time or money or attention, we all have to kind of make what we call trade-offs. Health economics is really thinking about how to make choices in the context of healthcare and health. Economics isn't just relevant, but I think really critical to understanding things like how to incentivize healthcare providers to coordinate care or encourage people to save for retirement." On a recent study (with colleagues at USC, UCLA and Contra Costa Health Services) looking at whether financial incentives could increase vaccination rates among the vaccine-hesitant "What we did is we invited unvaccinated members of this health plan, this Medicaid plan, to participate in a survey. And some of the people who were in the survey were randomized to receive an offer of financial incentives, either $10 or $50, if they got vaccinated in the next two weeks. Some people saw public health messages several different kinds of public health messages that we used in the survey and others got access to kind of an easy vaccine scheduling link. And I should say all of these, what we call interventions, were crossed. So some people got none of them, and some people got financial incentives and a public health message and an easy vaccine scheduling link and kind of everything in between. And then after the fact, we kind of looked at both what people said they would do. So did they say they were going to get vaccinated after they saw our public health message? And then, more importantly, did they actually go get vaccinated? And unfortunately, none of our nudges actually moved the needle here. So we just found that unlike in other contexts, like flu vaccinations, where we know that financial incentives can really increase uptake, that didn't work in this context. In fact, when we kind of looked at the data more finely and tried to kind of see how different groups responded, we found something actually somewhat troubling, which was that while as a whole people didn't respond to the financial incentives, people who said that they supported Trump in the 2020 election, for example, were less likely to get vaccinated if we offered them a financial incentive. The same is true for the kind of older respondents in our survey. You know, the people 65 and over, most of them had gotten vaccinated, but if we look at the people 40 and over, if we offered them a financial incentive, they were also less likely to get vaccinated. ... This is how we interpret the data. They had very strong beliefs about COVID-19 vaccinations kind of not being a good thing, and offering money to them seemed to kind of reaffirm that for them and almost encourage them to dig in their heels further. The reason I'm so excited about this project is there's been so much discussion about how to move the needle on vaccinations but really very, very little data on actual vaccinations. So most of the work in this area … has been focused on what people would say they would do. So you'd say if I gave you $50, would that increase your likelihood of getting vaccinated? And we were able to both ask that question, as well as look at people's actual vaccinations. And in fact, the funny thing is that we found that often people said they would do things and that just didn't show up. When we looked at their actual vaccinations. So many of the public health messages, we used seemed to increase the likelihood that people said they would get vaccinated in the next, say 30 days. But then when we looked at the actual data, that wasn't the case." On the role of economics in understanding low rates of palliative care usage "So palliative care is care from a team of specially trained doctors, nurses, social workers, and chaplains to focus on improving quality of life and reducing the disease burden for seriously ill individuals and their families. It can be provided alongside other treatments to people of any age facing serious ailments. The focus is really on treating pain and other distressing symptoms, addressing family needs, coordinating care, really focus on kind of the quality of life of patients and families. And there's actually a wealth of evidence that palliative care can improve quality of life. There's a now-famous study, for patients with advanced lung cancer, that showed that those receiving palliative care, in addition to regular treatment, not only had reduced symptoms of depression and a lower likelihood of hospital admission but also improved survival than those who received regular care. Kind of a stunning finding. I would say sometimes you know, a payer's savings is a health systems loss, right? So the incentives really matter. To the extent that palliative care saves money through a reduction in kind of unnecessary treatments or hospital readmissions, I think traditionally in our healthcare system, that meant a loss for healthcare providers, our system systems really changing, and hospitals increasingly for Medicare have incentives to kind of lower spending. And so maybe we'll see more of a push towards palliative care and growth in the next decade or so, but I think really up until very recently, it was really at odds with providers incentives to widely offer palliative care." On her research concerning Alzheimer's disease "So this is work that I'm doing mostly with Julie Zissimopoulos at the Schaeffer Center. And she's really the kind of Alzheimer's disease kind of expert. Where I fit in is, is really thinking again about incentives that different payers face and how that kind of relates to Alzheimer's disease. So we've looked at screening and Medicare, for example, and found perhaps not surprisingly after the fact that beneficiaries who are enrolled in Medicare advantage, kind of private Medicare plans, were much more likely to say they had received cognitive screening -- so to identify or to kind of set people on the path to identifying Alzheimer's disease or other dementia-related dementias -- than individuals who are enrolled in traditional Medicare. And why I say that's not that surprising at the end of the day, is that Medicare Advantage plans get paid for their enrollees based on what we call a risk-adjusted payment, so based on the severity and extent of disease facing their beneficiaries. And so people have found that they're actually kind of do a better job of screening in general and identifying health conditions of their members. And so this kind of carried over cognitive screenings in the work that we've done. We're also looking right now at, kind of the time path or trajectory of treatment for people who are diagnosed with Alzheimer's disease or related dementias in Medicare, both in, again, traditional Medicare and this Medicare advantage or Medicare managed care plans. And what we find is that actually, people in Medicare, in traditional Medicare, where care is very fragmented, are much less likely to be diagnosed outside of the hospital. Said differently, they're much more likely to be diagnosed in the hospital than those in Medicare advantage and their rate of hospitalization and other service utilization remains much higher than those in Medicare advantage. On top of that, it looks like they're also much more likely to die within a year of their diagnosis. And all of this at least seems to suggest that care really is not as well managed in traditional Medicare plans." On her future research goals "I think most of what I'd like to do is to try to take what people think are kind of commonly held beliefs or their instincts about, whether it's COVID-19 vaccinations or advanced care planning conversations, and try to test them with data. I think that's kind of really what motivates me at the end of the day, finding data to ask what's happening and can we improve outcomes for patients, for providers, really for everybody?"

Assistant Professor of Gerontology Joseph Saenz joins Professor George Shannon to discuss his ongoing work on rural-urban differences in cognitive ability among older adults in Mexico, as well as whether certain personality factors make people resilient to the negative effects of early-life disadvantage. Quotes from this episode On the focus of his work I focus my research on looking at how it's socioeconomic disadvantage throughout the life course relates with cognitive ability and late life. I'm interested in education. I'm interested in income, wealth and the resources that we have available to us throughout our lives and how this relates with better cognitive functioning, as well as lower dementia risk and the population of older adults of Latino origin here at the United States and also older adults in Mexico. On demographics and differences between rural and urban populations in Mexico One of the things that's very important about the Mexican population is we've seen a lot of demographic changes over the past century. In addition to seeing rapid population aging with the share of the Mexican population aged 60 and over increasing rapidly. We've also seen a large urbanization process where people are going from rural areas to urban areas. For example, back in 1920, only about 70% of the Mexican population lived in rural areas, but by 2010, this had declined to only about 20%. So a lot of people have been going from rural areas to urban areas. And this is important because in Mexico we see a lot of differences of a lot of disparities between urban areas and rural areas. Rural areas tend to be disadvantaged in several ways. They tend to have lower access to education. There's fewer schools for people to go to. And the educational quality that people got, especially if you look at several decades ago was significantly lower quality than their urban counterparts. Also in rural areas, we tend to see higher rates of poverty and various measures of SES. And we also see that the rural population tends to have less access to healthcare. This as the gap between the rural and urban areas in terms of healthcare access has shrunk a little bit over the past couple of decades, but there's still a disparity there. And so when you bring up the idea of the life course and where people live throughout life, I think this is especially important in Mexico, where we saw that rural to urban population shift, that many people who are living in urban areas now were living in rural areas as children. On his research looking at where people live throughout their lives In this more nuanced approach, what we see is that the people that had the lowest exposure to urban areas throughout life, those who lived in rural areas in early and late life, ended up doing the worst cognitively. And those who are doing the best are the people that lived in urban areas in early life and urban areas that late-life... And what we also see is that compared to people that stayed in rural areas throughout their entire lives, those who went from a rural to an urban area, also show advantages. So what it looks like we're finding in our current studies is that both early life, urban-dwelling and late-life urban dwelling are related with better cognitive ability. And there is an advantage that comes from moving to an urban area throughout life. On the negative impacts of indoor air pollution And then the other reason that we could expect to see these differences between rural and urban areas is that in urban areas, we know that people have high exposure to air pollution from the outdoor environment. When we look at pictures, for instance, say in Mexico City, we see the smoggy skies and we see this high level of air pollution that people are breathing in urban areas. However, in rural areas in Mexico, a significant portion of the population relies on solid cooking fuels. So this could be wood and coal and Mexico is primarily coal if people are using solid fuels for cooking. And when people use these solid fuels for cooking, particularly inside the house, you can imagine how quickly the pollution builds up inside the home. So people in rural areas have greater exposure to air pollution inside the home from solid cooking fuels. And we know that that exposure to air pollution is associated with poor cognitive functioning. And in my own work, looking at the effects of indoor air pollution from solid cooking fuels, I find that people who cook with these solid cooking fuels tend to have lower cognitive functioning and also more rapid cognitive. On the potential to improve outcomes We've seen several large policy changes in Mexico in the past couple of decades that are aimed at improving access to healthcare and primarily in rural areas. And so improvement of access to healthcare, access to health insurance, and regularly seeing doctors are something that we could use to improve cognitive ability and cognitive outcomes of older adults in rural areas. And last on the topic of cooking fuels, we know that one of the challenges and one of the reasons that people in rural areas are more likely to use these solid fuels is because maybe there's not the infrastructure to bring clean cooking fuels such as gas and electricity to more remote rural areas. Policy changes aimed at improving infrastructure to bring clean cooking fuels to rural areas and to educate people on how to cook with clean cooking fuels could be something very important to bridging these disparities that we see across rural and urban Mexico. On the role of cognitive resilience and personality characteristics in overcoming the negative effects of early life disadvantage What cognitive resilience is looking at is one's ability to not show the negative effects of stress. So people who are cognitively resilient can experience stress but don't show effects on cognitive functioning. They look like they're doing okay, cognitively, even though they're experiencing high levels of stress. In my work related to personality, I look at how personality characteristics are related with one's cognitive resilience or one's ability to overcome the negative effects of early life disadvantage. Early life disadvantage, being a stressor that I'm considering. So the personality characteristics that I tend to look at include a locus of control, which is how strongly one feels that he or she has control over their lives. And people who have an internal locus of control tend to think that the things that happen to them are the results of their own work. That they're the results of their own choices. Whereas people who have an external locus of control tend to believe it's external influences that affect their life. And so they're the ones that tend to believe that maybe the bad things or good things that happened to them throughout life are the example are, are the result of luck or of chance. Now, the other personality characteristic that I look at is conscientiousness, which has one's tendency to plan, one's tendency to be goal-oriented and to delay gratification. And when we look at the locus of control and when we look at conscientiousness, both of these affect how people tend to cope with stressors. So in my work on personality, what I do is I look at how personality relates with one's ability to overcome those effects. And we see that having an internal locus of control and having a conscientious personality are both independently related with one's ability to overcome the effects of early life disadvantage. On the importance of midlife research We also see a lot of focus on early life, a lot of looking at early life SES, a lot of research looking at education and childhood, but I don't think we see nearly enough work looking at mid-life. I think there's a big gap in our understanding of the courses or the trajectories that people take throughout life. We don't see enough about midlife. So I think this is another area that I'd like to go into more in terms of looking at midlife. So what are the specific occupations that people worked? What are the levels of cognitive stimulation and those activities also looking at midlife, we could also look at people's marital histories when they got married, whether they were married multiple times. So I think there's a lot of information out there on midlife that could be very valuable in predicting where people are going to be 10, 20 or 30 years down the road.

Assistant Professor of Gerontology Andrei Irimia joins Professor George Shannon to discuss brain imaging and brain health, including his work to determine who is most at risk for Alzheimer's disease after suffering a concussion or traumatic brain injury. Quotes from the episode On who is at risk for traumatic brain injury or TBI and adverse impacts from them Usually, injuries sustained early in life are the least likely to cause issues down the road during the aging process. And in fact, the brain is most robust to brain injuries in the first and second decades of life and injuries sustained during that period have typically the best outcomes and the best rates of recovery. And as we age, it becomes more and more difficult for the brain to recover after a traumatic brain injury. So, older adults, especially those over the age of 65, are at the highest risk for a poor outcome after a concussion or a more severe traumatic brain injury. After the age 40 or 45, there is a little bit of an increase in the risk for degenerative disease, including Alzheimer's disease. And that risk really increases after age 65. We have a preliminary study where we found that the biological age of the brain increases dramatically after a traumatic brain injury sustained after the age of 65, whereas for concussions sustained before that time, the biological age of the brain does not increase substantially at all. On sex differences in traumatic brain injury impacts It appears that in males, there is a higher risk for sequelae down the road up to about age 65, but for persons who are injured after the age of 65, there's actually a greater risk for atrophy of the brain in females, which is interesting because, as you already know, the risk for Alzheimer's disease is higher in females. And also the onset of Alzheimer's disease is typically after the age of 60 or 65. So one thing that my lab is very interested in is how exactly sex interacts with hormonal changes with the rates of biological brain aging and with other factors in determining the risk for Alzheimer's disease. There have been studies indicating without a doubt that there is an increase in the risk for Alzheimer's disease after traumatic brain injury, especially moderate to severe brain injuries. On identifying patients at risk for cognitive impairment after brain injury We've done a number of studies that have been funded by the National Institutes of Health and the Department of Defense on how we might be able to predict the risk for cognitive decline after traumatic brain injury. And we have studied cohorts of patients with Alzheimer's disease and compared them to healthy control adults who are age and sex match, who did not have a history of neurological disorders or have mental health disease. And, we found that it is actually possible using some tools that involve machine learning to predict the rate of cognitive decline based on acute imaging findings shortly after the injury. And we were able using these techniques to determine that the fact that we can actually identify the patients who are most likely to, uh, be at the highest risk for accelerated cognitive impairment six months or even one year or further after injury based on imaging scans. So this value, I believe is very valuable because it can identify patients who might benefit from additional monitoring and supervision by their clinicians and who might benefit from tailored therapies and from lifestyle changes that might decelerate the rate of cognitive impairment and might decrease the risk for Alzheimer's disease or other neurodegenerative diseases. On studying the brain and heart health of the Tsimane This is a very interesting and very important project that's been ongoing for essentially 20 years now. And I'm very fortunate to be part of a very large and talented group of interdisciplinary researchers who study the Tsimane people of the lowland Amazon basin in Bolivia. The Tsimane are a group of forager horticulturalists who live a very traditional lifestyle that does not rely on electricity or any of the amenities that we are used to in the industrialized world. They live in villages located in the forest of lowland areas in Bolivia very far from, uh, electricity from paved roads from modern medicine. And the reason they are very interesting to study is because they have profiles, especially pertaining to their cardiovascular health, to their neurological health and to their inflammatory profile that is very similar to that of our ancestors, many thousands of years ago. And here's a lot of interest in whether, Alzheimer's disease, whether cardiovascular disease and, and many other disorders are perhaps, at least in part, the result of a modern industrialized environment, where we have a large amount of processed foods being used, especially here in the United States where we have air pollution, water pollution where we have a lifestyle involving sedentarianism, which is, uh, very common in the United States and elsewhere in industrial life countries. And by contrast that Tsimane live a very active lifestyle and they live off the land. So, the men go hunting in the forest with bow and arrow. Their cooking does not involve trans fats or a lot of the unhealthy fats that are included in many of the processed foods here in the United States. So it's a very interesting natural experiment so to say, because their example allows us to study how Alzheimer's disease and cardiovascular disease might be in fact, predicated on some of the environmental factors that we have here in the United States and in other industrialized countries. And, my part of this collaboration is focused again, on the brain. And we had a study recently in the Journal of Gerontology where we showed that the brain of the Tsimane people after adjusting for head size, have a rate of volume decrease, which is considerably slower than in populations from the United States and Europe. And we found this to be a significant result because the rate of brain atrophy is very highly correlated with the rate of cognitive decline and with the rate of Alzheimer's disease risk. And, in addition to that, the Tsimane have a very low prevalence of cardiovascular disease. And in fact, a couple of years ago, our group published a paper in the Lancet showing that the Tsimane are the population at the lowest risk for cardiovascular disease out of all populations that have been studied by science. So this is a very unique group who seemed to have excellent cardiovascular health. And now with our study on the brain, we have shown that they also have a very slow rate of brain atrophy, which raises the question as to whether our lifestyle here in the United States and in other countries that are industrialized, where we have unhealthy diets and a sedentary lifestyle might actually increase the risk of Alzheimer's and risk of cardiovascular disease to extent that are highly significant.

Instructional Associate Professor of Gerontology Paul Nash joins Professor George Shannon for a conversation on the impacts of ageism, intersectionality and LGBTQ+ issues in aging, and the importance of talking about sexual health with older adults. Quotes from the episode On stereotypes and the impacts of ageism Well, there are some huge implications when it comes to ageism. So when we look on an individual level, we know that those people who have internalized ageism, so when they've acquired ageist attitudes across the life course, and then they reach older age themselves and they start to internalize those negative perceptions. We know that people that do that tend to walk slower, they tend to be more unstable on their feet, more likely to fall. They also have reduced cognitive functioning. So we actually start to see these stereotypes as we call it embodied. So we call it the stereotype embodiment theory, and we know that older adults have this more negative opinion of aging and being older themselves also have an average life expectancy that is about seven and a half years, less than those people that have a positive attitude about aging. When we look at society, we know that older adults make a huge contribution to society. We talk about billions of dollars a year in things like informal caregiving, even in terms of paid work, but also within the volunteer sector as well. So older adults make a continued service to society and to the economy, but it's often something that is not really discussed this often. So it's not really met. And when we start to prejudice against old people, we actually discriminate against their engagement in society. And as such what we're doing is actually making things an awful lot worse for ourselves. So what we need to do is start to actively embrace older adults and their diversity and understand accurate perceptions of aging rather than these stereotype myths that are widely held. Ageism is essentially prejudice against your future selves. So if we set up an ageist society, now when we read later life for ourselves, then we're going to be living and growing old in that age of society. So we need to start to challenge that younger people need to appreciate that actually having no wrinkles having gray hair or whatever, having wrinkles and gray hair is not a bad thing. Being older is not a bad thing. When we start to see all these anti-aging serums, well, that's kind of a fallacy. It's not going to stop you from aging. Every moment that we're alive, we are aging. Therefore, really the alternative to aging is death. And I don't think many people would like to wish that upon themselves either. When it comes to the wider social problems and the stigmas and things that I think we need to try and do is we need to be very much aware of our own language. And language, as you know, is incredibly powerful. So for example, we might see ageist stereotypes in greeting cards, and we will have a bit of a giggle about that, but, well, that reinforces the stereotypes. That adds to the issues that older people think that well, okay, I'm 60, I'm 70 I'm 80 as well, I must have cognitive impairment. Well, indeed, what we need to do is start to challenge these stereotypes. We have this assumption, or we paint this mental image in our head that all older people are going to be frail. All older people are going to have cognitive impairment. That's just not true. The majority of older adults, even the age of 80 are not going to be living with cognitive impairment. It's a disease state. Yes. We understand that people who, as they age are more likely to develop dementia, but the majority still don't. On intersectionality and LGBT issues in aging We know that the majority of older adults within the LGBT community are likely to be single. They're also less likely to have a biological family, so children of their own. And they're also more likely to be estranged from their own family, which has led really to the development of what we call family of choice, which is really where people surround themselves by friends and friends basically take that role of family within your own life. But that can be kind of challenging unless we have intergenerational family or intergenerational families of choice, because it may, be for example, that a group of people at the same age all start to require support and help at the same sort of times. We have to be very, very conscious of this. And then as I mentioned before, with that intersectionality, when we look at how racism and sexism and homophobia has developed across the last 50 years, we can start to understand then why, for example, gay women of color, and especially trans women of color are subject to the most forms of discrimination, which leads to problems in terms of accessing services, because they don't have faith in healthcare services, in support services, in any formal structure. So we have to make sure that there are targets and health messages. We need to make sure that we are removing some of these intersectional barriers so we can try and aim for a more equitable society. One of the problems that we have within the LGBT community is that there are very few quote-unquote safe spaces. And these often revert around bars around nightclubs, around places, for example, that you might meet with loud music and as an older adult, that might not necessarily be your ideal situation, especially if you're living with cognitive impairment, if you're living with a visual impairment or indeed issues with hearing as well. So we find that older adults often feel slightly isolated from these particular groups, which leads to larger issues with their social network, having reduced social networks and indeed self-isolate. And we start seeing then the problems around social isolation and loneliness that you mentioned earlier, George. And these are huge issues, not just within the LGBT community, but within the older adult population as well. But before we go down that rabbit hole, it is worth mentioning that older adults are not the most lonely in society. Actually, that is something that we can pass off to the younger generation, which arguably is partly down to that social comparison with social media. On the importance of talking about sex and older adults One of the problems that we've got and this really pervades through research as well, is we have this wide-standing assumption that older adults don't have sex. So as soon as you reach 50 ok and say, you're done, you never have sex again. We know this to be untrue, but research and mostly policy also stopped collecting data about older adults and their sexual health and their sexual behavior as well. So there's a lot of data that we just don't have on this population. So when it comes to sex and sexual health, what we need to do is make sure one, we're engaged in the older adult population and saying, well, we know you're having sex, but let's make sure we can do it in a safe way. We also need to make sure that sexual health screening is available for older adults because we have targeted interventions for youth groups, for hard-to-reach communities, but we don't have sexual health screening that goes around residential care, for example. And there's no reason why we build that. We also have to be very, very aware that older adults have different relationship styles. So gone are the days where every older adult is in the same relationship that they were in when they were 20 years of age. Indeed, now we're seeing increased divorce rates. We're seeing open relationships, polyamorous relationships, the same as we're seeing across other age groups as well. So we have to be very aware that for example, condoms, aren't just there to prevent pregnancy, but they're also there for sexual health. And we can take that across to, for example, HIV, where we see now that over 50%, nearly 60% of all those people living with HIV are older adults. And within this population, those are people over the age of 50. And that's been a real challenge, both in terms of healthcare providers also in terms of policy. So really what we need to do is open our minds and address some of these ageist assumptions that we have around older adults, and actually start to work with older adults as well, rather than making these assumptions about this homogenous group, which is exactly the opposite. It's the most heterogeneous group that you're going to get and actually work with them to understand some of these intricacies and understand some of these challenges that have been faced. So again, what we can do is try to make sure that these health messages are targeted and available for these specific groups. If we make these assumptions, the old people don't have sex well, we're automatically cutting them off from research or automatically cutting them off from health services. So really, I think one of the key lines is something that we used very, very widely in the UK. When working with older adults, we should be saying nothing about us without us. We should have that participating in inclusion work with older adults. Don't make assumptions around them and what aging actually entails when actually we've got these experts in the field, as it were, that are largely ignored from social policy and from research.

Associate Professor of Gerontology and Sociology Jennifer Ailshire joins Professor George Shannon to discuss the impacts of air pollution, global aging and how factors like location and education can influence the way we age. On the importance of place, or location, on aging Well, I think of place as one of the greatest supports and constraints on the way that we want to live our lives. So we envision a life for ourselves, our daily decisions, but it's really dependent on where we live. So for instance, I have a goal to be a very physically fit person and to engage in physical activity every day because I know that's one of the best ways to support my own health and aging. But if I live in a place where there aren't a lot of opportunities for me to exercise outdoors, maybe because I don't have access to good park space or other recreational spaces, maybe because of weather problems, it's going to have a constraining power on my individual choices. So a lot of people really want to eat healthy and exercise. And some people live in places that provide a lot of opportunity for that. And other people live in places where actualizing those wishes, those goals is really quite difficult. And then of course there are other factors about environments that really matter in terms of social stressors like crime or feeling safe in your neighborhood, and also more physical characteristics like, air pollution, which is one of the things that I've spent a lot of time studying while at the school of gerontology here at USC. On air pollution and aging We think of air as a physical characteristic. It's something that exists in the physical environment, but actually, maybe it's because I've been trained as a sociologist. I think of the air pollution as a social phenomenon because after all it's produced by humans for the most part. And so air pollution is located in places where we have a lot of industrial activity and where there's a lot of car traffic. So some people live in areas where they're closer to those sources of air pollution, and it usually is the case that those are lower income communities because throughout much of our kind of industrialized history in this country, people who could afford to live in a nicer area that was further away from sources of pollution would move and they would end up in a cleaner air environment. Now here in Los Angeles, we have poor air quality in a lot of places. On average, LA has worse air quality than a lot of cities in the rest of the United States, but there's also pockets of poor air quality here as well. So by the ports of Los Angeles and the ports of Long Beach, for instance, they have much worse air quality because a lot of that shipping and trucking activity, moving goods around. But living in California these days, particularly during fire season means that a lot of us are going to be exposed to poor air quality at some point during the year. And it doesn't at that point, it doesn't really matter what our own socioeconomic resources are. It's really just ways which way the wind blows and where the fires pop up around us. Most of the research had been conducted in younger populations in children and adolescents and in younger adults, but just in the past 10 years, it's become really clear that older adults are a vulnerable population and that they're more likely to suffer adverse consequences from chronic exposure to air pollution, and also from these acute episodes. So we've done a lot of work trying to grow that area of research in public health air pollution topics. And I think that it has really caught on, and there are a lot more people who will have been working in this area, trying to understand the negative impacts of air pollution on older adults. Our group was most interested in the aging brain. And so most of my research has been in trying to understand how air pollution might impact cognitive aging, increasing risk of cognitive decline or risk of cognitive impairment or the onset of dementia, for instance. I would say that until recently, although people understood that older adults were a vulnerable population, there wasn't necessarily a lot of direct attention on older adults themselves. So, those of us who work in this area of air pollution and its impact on health among older adults have been saying for a number of years that the federal regulatory standards that are used to regulate air quality, which had been really successful actually at improving our air quality over the past few decades since these regulations were codified and put into action at state and local levels, they tend to be driven by empirical evidence over the entire life course. They don't necessarily focus on the evidence for older adults specifically. And the problem that we've seen with that is that we tend to find that there are adverse health impacts at lower levels of pollution for older adults than there are for younger adults. So I think that we need to have a louder voice as gerontologists, geriatricians, people who are focused on the other end of the life course, that we need to have more of a voice at the table when these conversations are occurring about how we should be improving air quality. And I think that the EPA and state and local organizations are really receptive to this idea because they also see the need for it and the importance of it. I've already noted in federal documents that they have been highlighting the need to focus more on older adults. But of course we need that expertise kind of among their ranks. So I'd like to see more partnerships between the environmental sciences side and the policymaker and programming side with gerontologists who are focused on this population. On the protective role of education The importance of education for healthy lives cannot be overstated. It is simply the most important factor in all of the research that we've conducted and the aging brain is certainly no exception. But actually we think education is particularly important for the brain because we think what happens is that in early life people develop a cognitive reserve or some people call it resilience, but essentially we're building capacity in the brain to be able to deal with insults that might occur later in life. So for instance, something like building up brain volume or neural connections and early life, which can happen in part through education is really important when an individual gets older and they have exposure to toxic chemicals, for instance, that might cross the blood-brain barrier or enter the brain through other means that having that underlying reserve or that ability to deal with these external threats to brain health is really important. And people with higher levels of education seem to have a little bit more of that capacity. The other important thing about education though, is that it really sets people up for a lifetime of cognitive engagement. So people who have higher levels of education tend to engage in daily activities that are more likely to operate almost like a brain exercise, but it could be something as simple as playing instruments, speaking other languages and learning new things, taking classes later in life and, socializing with people, but anything that kind of keeps you sharp and keeps you on your feet is another good way to cope with the realities of some of the things that we're exposed to that might otherwise weaken the health of our brain. On global aging and Colombia I think if you ask most people, if you think of a place where there's aging happening, or there's a large population of older adults, where are those places? And they would say, think of countries like Japan, the United States, the United Kingdom, some of the countries in Western Europe, but aging is happening everywhere, everywhere, even in lower and middle income countries like Colombia that we didn't previously think of in terms of being an aging country. But Colombia, like a lot of countries in Latin America and other countries around the world, is experiencing a couple of key demographic changes like falling fertility rates and increased lifespan. And it's all happening very quickly. So Colombia will experience the same amount of aging in their population in about 20 years that the United States went through and, you know, in 50 plus years and some countries in Europe did and over a hundred year period. So this is a really opportune time to look at these countries that are undergoing this rapid transition to help us better understand aging. I also think that there is a potential to use the unique context of Colombia to help us gain insights, to help us understand aging in the United States population. So some of my colleagues in Colombia are working on a very famous study of genetics and Alzheimer's disease that are currently the home of one of the world's most important clinical trials of drugs and interventions for Alzheimer's disease at the moment. And it's because they have a cluster of people who are genetically predispositioned to get Alzheimer's disease at a very young age, in their forties and fifties. And so it's created this real world laboratory to understand a disease that we've just really been struggling to get a handle on. The discoveries made in Colombia will have far reaching impacts outside of that country, into the United States and other countries around the world, because we're all sort of dealing with this impending challenge of an increased number of people in the population who will have some form of dementia in their lifetime.

Julie Zissimopoulos is an associate professor in the USC Price School of Public Policy and the co-director of the Aging and Cognition Program at the USC Schaeffer Center for Health Policy and Economics, where she's also a senior fellow and the director of two NIA-funded centers that support innovative social science research on dementia. She recently spoke to us about her research using economic insights to better understand the impact of Alzheimer's disease on individuals, families, caregivers, and society. On the demographics of Alzheimer's disease: "People are living longer than ever. So, for example, today about 50 million Americans are aged 65 and older. It was about half that in 1950. And by 2050, US census projects about 20% of the population will be 65 and older. And age is one of the foremost risk factors for Alzheimer's and other dementias. So what does this mean for our future? Well, it means that without new treatments or innovations or ways to prevent or delay Alzheimer's and dementia, the number of persons living with this disease will be about 12 million by 2050. The risk of Alzheimer's is really a risk at older ages and it rises dramatically with age. So for individuals 65 to 79, about 7% of them will have dementia. But in your eighties, the risk of dementia is about 20% prevalence. And by 85 and older, if you live that long, about 40% of those persons will have Alzheimer's. It's also much higher for women than men. And that difference is not explained just by the longer lifespans of women compared to men. It's also about one and a half to two times higher for Blacks, Hispanics, American Indians, and indigenous Americans compared to whites. And we know a little bit about what explains some of the differences by race. Some of its explained by education and prevalence of chronic conditions that are associated with higher risk of dementia, like hypertension and diabetes, but it does not explain it all." On cognitive assessments at wellness visits "We collected data from a nationally representative sample of older Americans to understand better their use of annual wellness visit and the cognitive assessments. And what we found that was only about a quarter of them who received an annual visit also reported receiving a cognitive assessment. And this was higher for beneficiaries who were in Medicare Advantage-type plans versus those who were in the traditional Medicare plans. And this might have an important indication that these traditional benefit plans, the Medicare benefit plans, where there's direct service-related payment for a set of bundled services, like at the annual wellness visit, may not be a very efficient way to increase our cognitive assessments. We also, I think, have some opportunities to improve our policy around cognitive assessments. Right now there's no guidance about what constitutes a cognitive assessment or how it should be performed. So a clinician can use a structured tool, which we have many of, or they might just ask the beneficiary, the patient, if they're concerned about their memory. And so all of these factors may affect whether we are actually providing good early detection or not." On the costs of Alzheimer's "Along with the incredible health toll that Alzheimer's and dementia takes on a person and their families, it also takes an incredible, tremendous financial on the person who's living with dementia and their family. Alzheimer's disease leads to cognitive decline slowly destroying the brain functioning. It also leads for many to behavioral and psychiatric disorders and declines in ability to self-care, functional status. And all of this is extremely, extremely costly. So we estimated the costs for all the persons with Alzheimer's disease, other medical care costs in long-term care costs, and it's about $200 billion. But that's only a partial a portion of the costs. So as I mentioned persons with dementia need a lot of care and much of this care is provided by family members, unpaid care. And if you value the hours of family members caregiving, that's about a hundred billion dollars So we're talking about over $300 billion in costs of care for dementia. And this is more than the cost of cancer and heart disease combined . There is a growing literature… looking at what are these impacts on the unpaid care provided by family members and other caregivers. And there's very consistent evidence that there is negative health effects, particularly on mental health. Caregiving for a person with dementia, particularly as the disease progresses from mild symptoms to severe is a very stressful type of caregiving. There's a very long arm of financial impacts. For spouses, wealth is consumed to pay for long-term care. So care in a facility such as a nursing home can cost anywhere between $50-100 thousand a year. And most families don't qualify for Medicare that reimburses for the cost of long-term care. And for adult children who are caregivers there's impacts on their work productivity, their ability to maintain work in the labor force on their income. We don't have, as a nation, national family leave policies to support and pay for time away from work for caring for older family members with dementia or other conditions." On the need for policy changes "I think one important policy change is we need solutions to support family caregivers in the workplace, compensation programs. But this isn't going to be enough. Demographic trends suggest that family caregiving as the main source of care is likely not sustainable. People are having fewer children and they are more Americans with dementia. So we really need an insurance system to cover long-term care. The current system does not function well who, who take it up, tend to only be those at high risk with very high healthcare costs. So we need to be a little innovative here, maybe consider a voluntary auto enrollment in long-term care insurance with an opt-out much like what has worked well in the retirement savings market. Medicare could also help; we had a new benefit of Part D that covers drug expenditures and protects against very high out-of-pocket spending for those beneficiaries with high drug expenditures. This was very successful. Medicare could do something similar for long-term care, but it will be very costly. So we will need to figure out who will pay, how we will finance this and, and, and who is going to bear the costs of this. Will it be the younger generation through taxes on, say, health insurance premiums? If so, how are we going to make sure that they don't bear the full burden?" On future research goals "I'm very interested in continuing to try to understand how drugs for our chronic conditions are affecting our risk of Alzheimer's. Looking at anti-diabetics right now, and some of those drugs that are potentially increasing risk of Alzheimer's and dementia. I've been working on understanding and reducing barriers to early detection, how we might improve that and have some real impact there. And then there are many policy changes that are happening to Medicare, new benefits and Medicare advantage and these could all impact the care and quality of life for persons living with dementia. And it's important for us to understand what care systems best serve the needs of those individuals, protect against financial impacts for them and their families." On the importance of social science research "…Social science has a lot to offer in terms of identifying opportunities to reduce risk, reduce disparities in risk and improve quality of life and care, and really reduce financial burden. And at the USC Schaeffer Center for Health Policy and Economics and in collaboration with the school of gerontology, we have two NIH funded centers that support grant awards and mentorship opportunities for social science scholars who are interested in this area of research. Through efforts like this and growing this area of research, I think we can make immediate impact while we hopefully wait for clinical development of that drug that everyone is hoping for."