Of Mice and Men

For middle-aged mice, these are the best of times. Scientists now understand genetic factors that lead to the development of disease, disability, and death—in mice. Most importantly, researchers have found ways to improve the “healthspan,” the period of disease- and disability-free life before death—in mice. The question is whether the approaches they are developing will be applicable to people, and the ethical implications if they are.

The basic ideas are spelled out in a trio of “viewpoint” articles published in JAMA last week. S. Jay Olshansky, writing from an epidemiologic perspective, observes that over the past century, dramatic gains in life expectancy have been accomplished by reducing in mortality of children and young adults. But once these gains have been made, the only remaining way to lengthen life expectancy is by extending the lives of people at the other end of the age spectrum. Medical science has therefore concentrated on tackling the diseases of old age, one by one. Unfortunately, as Barzilai et al comment in their essay, “efforts focused on preventing individual diseases will have limited net effect on population health because one disease will be exchanged for another.” We’re already seeing this phenomenon: as fewer people die of heart disease, they develop and die of Alzheimer’s instead. Far better would be to tackle the aging process itself. Targeting the underlying driver of all the chronic diseases at once could, in principle, prevent or at least delay those disorders.

So, what do we know about turning off biological aging? We know there’s a gene in mice with the euphonious name rps6kb1 and if it’s “knocked out” (molecular genetics speak for “inactivated”), female mice live longer, healthier lives. We know there’s another gene called Sirt6 (short for Sirtuin 6), which is present in multiple mammalian species including humans, and if it is “overexpressed” (genetics speak for “turned on”) in male mice, they live longer. We also know that all creatures including people have “senescent cells,” cells that, old cells that start releasing all kinds of chemicals. When an individual has more than some threshold number of such cells, it develops chronic diseases, frailty, and is at high risk of dying. When the senescent cells of a mouse are destroyed, the mouse lives longer and without a long period of deterioration before death.

And what progress has been made in identifying drugs that achieve these goals in mice? And what about in people? Reportedly, the Interventions Testing Program, funded by the National Institute on Aging, has examined 26 “candidate drugs” for their effects on mice. They have identified 6, including the anti-inflammatory drug, aspirin, the anti-diabetes drug, acarbose, the immunosuppressive drug, rapamycin, and the estrogen, 17a-estradiol, as effective in some mice. Intervening in mice of an age equivalent to 70 human years has “extended life by more than 20 years and increase[d] health span even more substantially.” Other studies have found that the drug dasatinib (related to the anti-cancer drug, Tarceva) has a powerful effect in destroying senescent cells. In mice that are the equivalent of 80 human years, treatment with dasatinib combined with quercetin (a plant chemical found in green tea, red wine, apples, and other foods) increases survival 36 percent without increasing disability before death.

We don’t know whether any of these chemicals work in humans. And we have no idea at all whether they will produce side effects, though we do know that earlier attempts to interfere with cell lifespan were associated with the development of cancer. This is not entirely surprising, as the essence of cancer is uncontrolled cell proliferation. So even the very upbeat article by Tchkonia and Kirkland, the third of the triad, ends on a cautionary note: “…Patients should be advised not to self-medicate with senolytic agents or other drugs that target fundamental aging processes in the expectation that conditions alleviated in mice will be alleviated in people.”

If, years from now, human studies indicate the drugs or others like them are effective, we will have to deal with the ethical implications of extending the “healthspan.” What will they cost? Will everyone have access to such medications? Will we create greater inequality within society? Between countries? Banning such research on the grounds that a ballooning of the elderly population is unsustainable is almost certainly going to be impossible—the lure of more disease-free life will be irresistible. But we can begin to think about the consequences of our brave new world.

Make Our Lives a Blessing

Kaiser Health News ran an article this week about “the secret happiness as you age.” It features the story of a 76 year old man who, despite severe heart disease, diabetes, glaucoma, and osteoarthritis, describes himself as a “happy guy.” He can’t see well, he can’t drive, and he has to rest after walking short distances—really short, like 10 yards. So how does he manage to be happy?

His secret is that he focuses on those things in life that do bring him joy—listening to music and audiobooks, and writing. He also derives pleasure from helping others in small ways. The article concludes with a quote from a geriatrician who says that “the real key to happiness at every age and stage—particularly old age—is not material things, but gratitude for life’s simple blessings, like laughter among friends or watching a sunset with a loved one.”

The message that frailty doesn’t have to spell misery is a refreshing one. Readers of this blog know that I spend a great deal of time discussing frailty: defining it, advocating screening for it, and promoting an “intermediate” approach to care for people who have it. I lament the disproportionate time and energy spent on addressing robust old age and dying, two important states but not where most older people spend most of their time. The Kaiser Health article is an important reminder that we don’t need to hide frail people from view as though they carry an unbearable, unmentionable stigma. But what is missing from the piece is the recognition that while individuals who are frail can take steps to make their lives rewarding, the larger society has an important supportive role to play. 

Creating and disseminating the technological aids that can make life enjoyable are crucial: without his audiobooks and his virtual assistant (in the example given, Amazon’s Alexa), achieving satisfaction might have been impossible. We need to make age-friendly environments, like those promoted by the World Health Organization’s “Age-Friendly Cities and Communities Program.” This means building walkable communities, providing appropriate transportation, and linking service providers to individuals. It means developing accessible housing and means for civic participation, along with access to medical care. It means joining the AARP Network of Age-Friendly Communities or local organizations, such as the Massachusetts Healthy Aging Collaborative. Only then will happiness among frail elders be the norm rather than the exception.

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No Man is an Island

The United States produces outstanding reports about just about any health-related topic you can imagine. Some of the reports are produced by branches of government: for example, the CDC issues a series of Vital Statistics Reports that summarize and analyze data about deaths, births, and diseases. Other medically oriented reports are produced privately, and the crème de la crème of such reports stem from the National Academies of Sciences, Engineering, and Medicine. 

Created by congressional charter in 1863 and signed into law by President Lincoln, the National Academy (as it was called until recently) is a private institution charged with providing “independent, objective analysis and advice to the nation to solve complex problems and inform public policy decisions related to science, technology, and medicine.” Its recent report, Families Caring for an Aging America, is in a long tradition of distinguished monographs. Some of these have gone on to be extremely influential, such as To Err is Human: Building a Safer Health System, the report published in 2000 that triggered a serious campaign to enhance the safety of hospital care), others languish on library shelves. Which category the new report on caregiving will fall into remains to be seen. So far, the response of the most influential newspapers has been resounding silence. It deserves better.

The theme of the report, the drumbeat intoning relentlessly throughout its seven chapters and eight appendices, is that no man—or woman—is an island. We are parts of families, whether defined biologically or otherwise, of neighborhoods, and of communities. In the words of the poet, John Donne:

                   

No man is an island,

Entire of itself,

Every man is a piece of the continent,

A part of the main.

As we age and develop assorted frailties, we rely increasingly on those others in our lives to help sustain us. The truth is that younger people are also parts of families, neighborhoods, and communities, and they, too, depend on others for sustenance, support, and succor. The notion that individuals act and think in isolation is a myth. Americans may be more individualistic and less communal in their attitudes and behavior than any other group in human history, but we are still fundamentally social beings. The collision between myth and reality is starkest, however, for those who are physically or cognitively frail, most commonly due to age-related changes.

In medicine, the relentless focus on the individual results in a paradox: in the words of Families Caring for an Aging America, “care delivery simultaneously ignores and relies heavily on family caregivers to provide ongoing support to older adults with cognitive and/or physical impairments.” According to one national survey, only 1/3 of family caregivers had ever been asked by a doctor, nurse, or social worker what they needed to care for their relative, and in a second survey, only 1/6 of caregivers had been asked what they needed to care for themselves. The evidence that caregivers are important is ample: the availability of a family caregiver is associated with fewer and shorter hospital stays for older adults, that caregivers reduce home health care use generally, and that they delay nursing home entry.

             The facts in the new report are not new.  But Families Caring for an Aging America is unusual in emphasizing the role of family caregivers in medical care as well as personal care, for dwelling on the effect of caregiving on the quality of health care as well as on the mental health and pocketbook of the caregiver. An entire chapter is devoted to “family caregiver integration with health care and long term services and supports.” The report assembles all the evidence demonstrating both the crucial role of family members (in the most generic sense) and the obstacles to their fulfilling that role. Caregivers participate in a wide variety of activities on behalf of their elderly charges, including making decisions about stopping and starting medications, selecting alternative treatment options when confronting a major life event, choosing whether to institute or continue life-support, and opting to move to congregate living, assisted living, or a nursing home. Despite the importance of family in older adults’ decision-making, “little attention has been directed at developing interventions to support older adults and their family member when confronting difficult decisions.” Moreover, caregivers are directly involved in the administration or supervision of a variety of sophisticated medical treatments, ranging from peritoneal dialysis to ventilators. Yet, doctors and nurses do little to provide those caregivers with the knowledge and skills they require to competently perform these tasks.

The report goes further: it outlines a strategy for change.

Change must begin with a “reorientation of care systems to a focus on family-centeredness.” That means health professionals need to listen to and honor the person and family’s needs, values, preferences, and goals of care. It means taking into account the physical and mental health of patients and caregivers, and engagement with their community. It entails developing a plan of care that is based on the patient’s needs and wants as well as what the family needs to provide support. It will require that the patient and family have access to timely, complete, and accurate information as well as the tools necessary to make shared and informed decisions. Overall, families need to be integrated into the care team to provide care and supportive services that are accessible, comprehensive, continuous over time, and coordinated across settings.

Medicare has taken a few small, shaky steps in the direction of implementing this model. CMS introduced a billing code that allows physicians, NPs, and PAs to be paid for time spent coordinating care for patients with multiple chronic conditions, without requiring that the patient be present and a physical exam be performed, the previous sine qua non of a “visit.” New home health agency regulations require that the plan of care developed, say, by a visiting nurse, identify the primary caregiver and assure that individual gets the necessary education and training to play the role required of him or her in the overall plan. But much, much more is needed and the report acknowledges this.

Families Caring urges the next US president to create a National Family Caregiver Strategy. Executive orders and new federal legislation should then “explicitly and systematically” recognize the essential role of family caregivers. This means designing specific assessment measures, programs, and research—and the funding to support them. In particular, the strategy should include mechanisms for Medicare, Medicaid, and the VA to identify family caregivers and assess their needs in the delivery of health care and long term services. It should involve directing CMS to develop, test, and implement payment reforms to motivate providers to engage family caregivers and to provide them with evidence-based supports. It should increase funding for programs that support family caregivers and explore adopting additional policies to provide economic support for working caregivers. And it should both collect data to monitor and track the experience of family caregivers, and also develop a multi-agency research program to evaluate caregiver interventions.

It’s a bold vision. And it will need to expand even further, starting not just with the doctors and nurses who care for older patients, but including the educational and training programs for those nurses and doctors. Medical school and nursing school are critical venues to model the kind of collaborative, team-based decision-making the vision assumes. It will need to go back even further, to high school and college, planting the seeds for the role that we will each play as a caregiver and a health care partner by educating young people about all the stages of human existence.

Home Not Alone

Last June, Medicare announced preliminary results from its “Independent at Home” demonstration project. They showed the program provided high quality care and at the same time saved money. Not only that, but the population it served was the sickest of the sick and the frailest of the frail—people with multiple chronic conditions who needed help with personal care. But the reports in the news media didn’t explain what exactly the program did. Now, a study in the latest issue of Health Affairs explains how the program works and analyzes its achievements to date. 

The new study confirms the earlier reports: participants in the study had lower rates of acute hospitalization, which saved Medicare money. They also had a lower risk of nursing home admission, which saved Medicaid money. But the results so far—the analysis is based on data from the first year of a three-year pilot project—are modest. In one group of program participants, the hospitalization rate fell 14%; in a second group (the criteria for enrollment were somewhat different), the hospitalization rate fell only 1%. And understanding the analysis is almost impossible for the general reader. Not only were there two different sets of participants, with slightly different characteristics, but there were four different comparison groups. Then the authors invoked something called “entropy balancing.” The most it seems to me reasonable to conclude at this point in time is that the program isn’t hurting and it might be helping both patients and Medicare’s budget woes. But the benefits, if they exist at all, are likely to be small.

But what really struck me about the program is the description of what it actually involves—and what it doesn’t. Independent at Home does not support ongoing, comprehensive primary care provided in the home. It is nothing like a program reported on in the media at the same time that the Health Affairs article came out, a program on Long Island, New York that in fact moves all of health care into the home of its frail enrollees. That House Calls program sends doctors and nurses into the home and offers simple lab tests, basic x-rays and services such as physical therapy in the home. The doctor or nurse who visits the patient goes back again and again, providing continuity. The Independent at Home initiative, by contrast, provides a single home assessment each year that involves a history, physical exam, and lab tests, including a screen for depression, a review of medications, and a needs assessment. The upshot of this home evaluation is the development of a “plan of care” that is transmitted to the primary care physician for implementation. That plan might include referrals to social work or palliative care, but the individuals providing these services are not members of the primary team. When the patient develops an acute medical problem, nobody comes to the home to assess the patient--the primary care doctor is called. No medical personnel return to the home until it’s time for the next annual home assessment.

How can such a limited program possibly work? And if it does, what does that say about our usual way of providing care? It’s worth noting that the design of Independent at Home took into account the utter failure of an earlier demonstration program that tested the effectiveness of  “care coordination” and “disease management.” In this model, which had been instituted by 34 programs and which the Congressional Budget Office pronounced ineffective, patients were encouraged to participate actively in their own care and a case manager helped them negotiate the system and facilitated communication among all those involved. Perhaps not surprisingly, a system that relies on very frail older people, many of whom suffer from cognitive as well as physical impairments, to self-manage their care is fraught with peril, however effective such an approach might be in other patient populations. So the new model, the basis for the Independent at Home project, has as its centerpiece a plan of care and it’s the primary care physician, not the patient, who is supposed to implement the plan. It draws on studies such as the University of Pennsylvania’s transitional care program that found that a single home visit by a nurse  after a hospitalization could markedly decrease the risk of readmission to the hospital the following month.

Conceptually, the new model is an improvement over its care coordination/disease-management predecessor. It makes sense to determine whether anything short of comprehensive home-based primary care can provide high quality, cost-effective care, since the more all-encompassing home care won’t be cheap. But why place the responsibility for implementing the “care plan” squarely on the shoulders of the primary care physician, when we already know that most primary care physicians aren’t equipped to care for frail elders? Why rely on the primary care doctor to follow the plan when we already know from studies of geriatric consultation done years ago that when doctors receive recommendations for how to take care of patients that are based on unsolicited medical consultations, they ignore them? Why not focus on the caregiver as a crucial and untapped resource? 

The older patients who enroll in Independent at Home need help to get by day to day. Almost by definition, they have caregivers. Only when we involve the caregivers in medical care (and not just in providing personal care or crisis decision-making) will we be able to provide the kind of care that patients want and deserve. Yes, we will need a home visit to develop a plan—a plan which must reflect the values, preferences, and resources of the patient and caregiver. And yes, the physician needs to be involved in implementing the plan. But so, too, does the caregiver.

I stumbled on it purely by accident. I was looking for a picture to illustrate "diversity" for a talk I am preparing, and I seemed to remember that the World Health Organization had some beautiful photos in its earlier reports. Maybe what I liked best about those photos is that they capture the beauty and the humanity of their subjects without insisting that everyone smile for the camera. As it turns out, I didn't find what I was looking for but I discovered that on the very day I was searching, the WHO released a brand new report. It doesn’t have a very snazzy title—it’s called World Report on Ageing and Health—but it’s a remarkable and inspiring document. 

Not surprisingly, none of the major US newspapers breathed a word about its release. Maybe the reporters just haven’t had time to go over it: it is, after all, 260 pages. Or maybe they figure that what’s happening in the rest of the world isn’t terribly germane to the US. Perhaps--and I suspect this is the real reason--the media don't want to think about aging. In fact, the report is brimming with fascinating observations and interesting insights, many of which are relevant to the United States both in terms of our own aging population and in terms of national security. There is so much in here worth commenting on, that I think I will devote more than one blog post to the report. Let me begin by sharing some of the most astonishing things I learned in the first half of the report.

The report begins by suggesting that rather than thinking about expenditures on older people as pure costs, they should be seen as investments. It points to a study done in the UK a few years ago which calculated that if you put everything that the government spends on old people in one column (pensions, health care, other social welfare programs) and you put the contributions of older people in another column (taxes, consumer spending, work), you come up with a positive balance. At least in England, the net contribution of older people amounts to 40 billion pounds per year.

One of the most startling differences between this new report and its predecessor is that today's version defines healthy aging as the process of developing and maintaining the functional ability that enables well-being in older age. iI like that. All health care systems in all countries, the authors argue, should have as their single goal fostering the functional ability of older people by supporting and maintaining their intrinsic capacities and by enabling those with diminished functional capacity to do the things most important to them. This is a marked improvement, in my view, from the last major WHO report, Active Ageing, which came out in 2002, that talked about "optimizing opportunities for health." Then, health was the ultimate objective; now, health and healthcare are means to an end and that end has to do with the ability to function in society.

The description of what health in older age looks like in different countries is both intriguing and sobering. My attention was drawn to a single chart showing the percent of the population age 65-74 and the percent age 75 and older with limitations in one or more activities of daily living, by country. Only a handful of countries were listed. But the gap between the worst off and the best off was shocking—as was the revelation of who occupied the extremes. In first place is Switzerland, with fewer than 10% of the 65-74 year olds suffering a limitation in function and fewer than 20% of those over 75. In last place is Russia, with 60% of the younger old and 80% (that’s not a typo) of the older old reporting at least one ADL deficit. I haven’t quite figured out how this relates to Putin’s policy in Ukraine and Syria, but I suspect there’s a connection. There's something very rotten in the state of Russia.

On a more optimistic note, the chapter on “Health Systems” gives some uplifting examples of countries that have introduced novel approaches to improving the well-being of their older populations. Ghana is making an effort to harness its well-established system of community health workers to meet the needs of older people. And Brazil has begun integrating aging into its national family health strategy: it is using multidisciplinary teams comprised of physicians, nurses, and physical therapists, psychologists, nutritionists, occupational therapists, and others to work in community centers and to go into patients’ homes to deliver care.

More to follow…

Til Death Do Us Part

Why did this image go viral? In case you haven’t seen it before, it depicts a couple who were admitted to separate rooms in a Georgia hospital. Thanks to the wisdom of the nursing staff—and some bending of the rules—they were reunited. I think the photo struck a chord because it captures the important reality that what matters most as we get older—and perhaps at any age—is relationships.

We devote an inordinate amount of effort when we are younger to being “successful,” which we tend to define in terms of fame and fortune. And then, when we retire, we focus on living longer, on diet and exercise, on health and on experiences. But what so clearly mattered most to the couple in this photo is each other. Yes, the oxygen flowing through the plastic tubing is important. Yes, the intravenous catheter (not visible in the photo but I’m reasonably sure it was there) was useful for delivering potentially life-prolonging medication. But what makes life meaningful above all is our connections to others.

Lisa Berkman, a prominent social epidemiologist, has found compelling evidence that social networks—our links to our community—even affect our physical health. They influence whether we get a heart attack or stroke in the first place and how we fare if we get one. They affect our propensity to develop cognitive impairment and how well we cope if dementia strikes. But perhaps George Vaillant said it best when summarizing his book, Triumphs of Experience: the Men of the Harvard GrantStudy. This ambitious, longitudinal project followed 268 men who graduated from Harvard in the 1940s with a series of in-depth interviews over the course of their lives. Of course, generalizing rom these privileged Americans, all male and all born in one era, to the rest of us is risky. But despite their talents and their opportunities, these men had their share of alcoholism, of poverty, of suffering, and of disease. The inescapable conclusion that Vaillant reached  was, as he put it himself: “It was a history of warm, intimate relationships—and the ability to foster them in maturity—that predicted flourishing in all aspects of these men’s lives.” And that's the message conveyed by the photo of the two nonagenarians in their hospital johnnies, holding hands.

Helping the Other Half

There’s nothing much new in the latest edition of the Alzheimer’s Association Alzheimer’s Facts and Figures, which came out last month. Once again, the report documents that about 43% of people age 75-84 have Alzheimer’s. Since no more than 75% of all dementia cases are due to Alzheimer’s disease, that means that over half of  people in this age group have dementia of one kind or another.

The proportion varies depending on how dementia was assessed and on the ethnic, geographic, and gender composition of the people studied. But despite an enormous amount of effort and much progress in the domain of understanding the pathophysiology of Alzheimer’s disease, the Alzheimer’s Association reminds us that there is no drug available today that slows or stops the death or neurons that causes Alzheimer’s disease.

The federal government’s National Alzheimer’s Project Act and Obama’s BRAIN (Brain Research Through Advancing Innovative Neurotechnologies) initiative are redoubling the effort to find a cure. That would be terrific—though we should remember that the last concerted effort to wipe out a chronic disease, the War on Cancer, was launched in 1971 and is still being fought.

But what about the other half—those older people who don’t have dementia? Is there anything that medicine should be doing special for them?

A new report from the well-respected, non-governmental, non-profit Institute of Medicine released last week addresses this question. Entitled Cognitive Aging: Progress in Understanding and Opportunities for Action, the report makes ten recommendations for collecting data, engaging in research, developing programs, and providing resources that seek to maximize cognitive function in older people who don’t have dementia. It’s an intriguing report, principally because it focuses on what is most important to older people and is the essence of geriatric medicine—function, rather than disease. The authors cite an AARP survey of members in which fully 87% identified “remaining sharp” as one of their major concerns. Older individuals and their families are concerned with optimizing mental performance. They are alarmed by the recently described disorder, “Mild Cognitive Impairment,” a condition that does not meet the criteria for dementia but affects the ability to function in day to day life, whether or not it progresses to full-blown dementia.

The study is also of interest because of it public health angle—it draws attention to the major societal consequences of age-related cognitive decline, things like traffic accidents (as people with impaired judgment or slow reflexes continue to drive) and financial fraud (resulting from impaired decision-making on the one hand and minimal consumer protections on the other). The recommendation to develop assessment tools, educational programs, and improved regulations, as well as alternative means of transportation, have the potential to maintain quality of life for older individuals and to lower costs.

The report makes common-sense suggestions for preventing age-related cognitive decline: being physically active, remaining socially and intellectually engaged and getting enough sleep. Unfortunately, there is no more evidence that these measures will maintain cognitive function than there is that they will prevent dementia. That is, they might help and they can’t hurt. But to suggest that they are proven to be effective is, alas, to overstate the case.

Despite succumbing to the temptation to offer a little bit of hype along with a lot of wisdom, the report’s authors make a valuable contribution by reminding us to pay attention to the other half. Its broad societal focus is welcome, as is the recognition that it is function rather than disease that matters most to the majority of people as they age.