Don't Fall for It

In an earlier posting, “Break a Leg,” I recommended that frail older people use hip protectors to prevent hip fractures. The data, at that time, were suggestive but not conclusive. A recent study, unfortunately, definitively argues against the benefits of hip pads. In an article published in the Journal of the American Medical Association, Dr. Douglas Kiel and his colleagues reported on a large randomized trial that used a very elegant approach to answer a difficult and important question (D Kiel, J Magaziner, S Zimmerman et al, “Efficacy of a Hip Protector to Prevent Hip Fracture in Nursing Home Residents,” Journal of the American Medical Association 2007; 298: 413-422).

Earlier studies were plagued by all sorts of problems: people didn’t like wearing the hip pads, leading to what was called “poor compliance,” making it hard to analyze the results. The hip pads studied were made of differing materials and some of the pads may actually have increased the chance that a fall would cause an injury to the hip bone itself rather than merely to the surrounding soft tissue. This new study used a hip protector that had been shown to have the desired biomechanical properties. It was conducted in nursing homes, where the frailest elders live, the people with the highest risk of falling and fracturing a hip. And the investigators did something very ingenious: they used each nursing home resident as his own control. Every individual in the study wore a one-sided hip pad on either the right or left hip. The researchers would then observe all the residents over time to see whether the protected hip was any less likely to be fractured than the unprotected hip.

The study was carried out in 1042 individuals with a mean age of 85 who lived in one of 37 nursing homes located in Massachusetts, Missouri, or Maryland. What the authors found was that the nursing home residents were just as likely to fracture the protected hip as the unprotected one. In fact, the study was stopped early because preliminary evidence was so overwhelming that the hip pads, contrary to everyone’s hopes and expectations, simply did not work. Even when the analysis was restricted to the 334 nursing home residents who wore the pad more than 80% of the time, there was still no difference in fracture rates between the protected and the unprotected hip.

It would have been great to be able to say, at last, that hip pads really work. But at least we now have the necessary information with which to conclude that they don’t. Now we know that we shouldn’t spend money on hip pads. I have to retract my earlier recommendation. It’s time to look for other strategies.

A New Test for Alzheimer's Disease: Hype or Hope?

The New York Times reported today on “a blood test” for Alzheimer’s disease (Andrew Pollack, “Progress Cited in Alzheimer’s Diagnosis,” NYT October 15, 2007). Is there actually such a test? If not, is one imminent?

Don’t hold your breath. I’m old enough to remember the eye drop test for Alzheimer’s and the skin biopsy for Alzheimer’s, neither of which panned out, not to mention the serum beta amyloid test and a few spinal fluid tests. What the news media are reporting appeared in the on-line edition of Nature Medicine yesterday in a letter-to-the-editor, not in a peer-reviewed article (Sandip Ray, Markus Britschgi, Charles Herbert et al, “Classification and Prediction of Clinical Alzheimer’s Diagnosis Based on Plasma Signaling Proteins,” Nature Medicine online, October 14, 2007). This means the findings have not been written up in an article and subjected to careful scrutiny by other scientists who are experts in the field. The letter, penned by 25 scientists, notes that the group has been studying over 100 different proteins found in the blood of patients with a diagnosis of Alzheimer’s disease to see if some combination of them might serve as a diagnostic test. They have found that a particular pattern involving 18 different proteins successfully classified 8 out of 9 patients with Alzheimer’s disease (confirmed at autopsy) as having the condition. The results, while interesting, are far too preliminary to be of interest to the general public.

If we did have a test that could accurately diagnose Alzheimer’s disease, would it matter to the millions of people with cognitive impairment and their families? Probably not. Right now, physicians can already diagnose Alzheimer’s disease with 90% accuracy, based on a careful history and physical examination together with existing laboratory tests. Even more crucial, while it is useful to diagnose dementia (whatever the cause) so as to begin planning for the future, it’s only important to distinguish Alzheimer’s disease from other forms of dementia to the extent that we have good treatments specific to Alzheimer’s. Today, the only “treatment” we have for early Alzheimer’s disease is a group of drugs known as cholinesterase inhibitors—drugs such as Donepezil (Aricept). This medicine can temporarily improve cognitive function a very modest amount. Its effectiveness is so questionable that the British NICE (National Institute for Health and Clinical Excellence) recommends against its use in patients with mild dementia (see my earlier blog posting, “Americans, Alzheimer’s, and Aricept,” February, 2006). It doesn’t cause any harm if it’s administered to patients who prove to have a non-Alzheimer’s dementia, such as vascular dementia.

One day, when we have good treatments for early Alzheimer’s disease, it will be important to make the diagnosis early and accurately. Today, what a good doctor can do is good enough.

"The Denial of Aging" is Available in Paperback

Putting the Brakes on Technology

In a dramatic twist of fate, one of the world’s premier heart surgeons recently underwent cardiac surgery utilizing a technique he had devised, at the hospital where he had practiced. What gave the story added interest was that the surgeon, Dr. Michael DeBakey, was 97 years old at the time of the operation, and it was carried out against his express wishes.

As is recommended for all patients, Dr. DeBakey had an advance directive: he had stated, while in good health, what approach to medical care he would want if he became ill and was unable to speak for himself. He specifically indicated that he would not want to undergo major surgery. A cardinal principle of contemporary medical ethics is that it is the right of patients to make just this sort of decision and the obligation of physicians to follow their wishes. To respect a patient’s preferences as long as he is able to speak for himself—as happened with Dr. DeBakey during the nearly six weeks following the onset of symptoms—and then to disregard those wishes once the patient loses the ability to make decisions—as occurred when Mrs. DeBakey reportedly stormed into a late night hospital ethics committee meeting and demanded that the surgery take place—violates the hard-won respect for their autonomy that patients have gained over the past twenty years.

Much of the commentary about the case has centered on whether a patient’s wishes can be overridden, even by loving family members. What has largely been left out of the discussion is whether it is ever appropriate to perform invasive, dangerous, and expensive surgery on 97-year olds—even if they want it.

The operation performed on Michael DeBakey involved putting him on cardiac bypass and opening the aorta, the artery that carries blood from the heart to most of the major organs of the body. The damaged part of the aorta was then replaced with a synthetic graft. The risks were high—in a group of elderly patients who had the procedure, the oldest of whom was 77, 18% died. Moreover, simply surviving the surgery does not mean returning to one’s usual state of health in a matter of a few weeks. It typically means, as DeBakey experienced and as his physicians anticipated, an extended hospitalization marked by reliance on machines, marred by multiple complications, and fraught with considerable suffering. Dr. DeBakey spent three months in the hospital, much of the time unable to speak or eat, let along get out of bed, read, or interact with others. He was attached to one machine for breathing and to another machine to clear wastes from his system. He was fed through a stomach tube. The cost of his hospital stay is estimated to have exceeded one million dollars.

Dr. DeBakey is glad to be alive—and I am delighted for him that he survived his ordeal. But how many people should we subject to the grueling treatment DeBakey endured for a chance of a few more weeks or months of life? Is it reasonable for 99 or perhaps 999 people to suffer for days or months, only to die from complications of the surgery, because very occasionally, one person might live?

The number of potentially life-prolonging technologies offered by contemporary medicine is proliferating rapidly. The implantable cardioverter defibrillator jolts the heart back to normal if an irregular, life-threatening rhythm develops in patients who have had a heart attack. The left ventricular assist device is a partial artificial heart used in patients dying of heart failure. Sophisticated biopharmaceuticals created by biotechnology are also multiplying, drugs typically used in patients with extremely advanced cancers. Some of these technologies offer a chance of additional months or even years of life to people in their prime; but do they make sense, especially when they are invasive and costly, in the oldest old?

When the baby boomers begin turning 65 in the year 2010, they will account for 13% of the U.S. population; by 2050, they will make up 20.6% of the population. Medicare expenditures for this group—the money spent by the government insurance program for the elderly alone—are projected to soar from the current 2.6% of the Gross Domestic Product to 9.2% in 2050, and technology will account for over 50% of the increase in costs. If we are to have the resources to spend on public goods other than health care—on education, on national parks, on highways—not to mention to spend on medical care for poor people and for children—we need to put the brakes on technology.

In a rich country like the U.S., this does not have to mean rationing care based on age alone. But surely the place to start is to limit treatment that is burdensome and expensive, that has a miniscule chance of success, and that is proposed in someone who is at the very end of life. We need to accept human mortality and, as a matter of practice and of policy, concentrate on improving the quality of life of older people. This means assuring compassionate nursing home care, coordinated management of chronic diseases, and competent palliative care as death approaches, rather than using ever more technology to try to eke out a little more life. And it means systematically considering cost and life-expectancy in decisions about reimbursing high technology medical care.

An abridged version of this article appeared on Project Syndicate (www.project-syndicate.org). It was translated into 7 other languages and distributed to over 300 newspapers worldwide.

How Different Are We?

Ample evidence indicates that African Americans, on average, favor more aggressive medical care near the end of life than do white Americans. This translates into more days in the intensive care unit and more unsuccessful attempts at cardiopulmonary resuscitation before death, and it means less hospice care. This phenomenon is typically attributed to differences in values between minorities (Asian Americans and Latinos express similar preferences to blacks) and whites or to a deep-seated mistrust of the medical profession—or both. In a new study released today, my colleagues and I suggest that lack of understanding of their health status may play a role as well. Moreover, showing patients a video can overcome poor comprehension.

In our study, “Using Video Images of Dementia in Advance Care Planning,” (Archives of Internal Medicine 2007; 167:828-833), we looked at advance care planning, at what approach to care patients say they would want in the future. Specifically, we asked how they would want to be treated if they developed advanced dementia, a condition in which they were dependent on others for their most basic needs such as eating and going to the bathroom and in which they could speak only a few words. Our strategy was to give the research subjects a verbal description of advanced dementia and then ask them whether they would want life-prolonging care (conventional comprehensive care), limited care (excluding CPR and ICU care), or comfort care (treatment of symptoms). Next we showed each of the 120 individuals enrolled in the study a 2-minute digital video of a real person with advanced dementia. The film showed a nursing home resident being fed by her daughters; it showed the daughters asking her questions and failing to elicit a response; and it depicted the daughters transporting her in a wheelchair. The accompanying narrative was identical to the previously delivered verbal description of advanced dementia as a progressive, ultimately fatal neurologic disease that causes profound impairment in memory, thinking, and judgment. After watching the video, the research subjects were again asked what approach to medical care they would favor.

What we found is that before watching the video, 21% wanted life-prolonging care, 18% wanted limited care, 50% wanted comfort care, and 11% were uncertain. After seeing the video, nobody favored life-prolonging care, 8% wanted limited care, 89% said they wanted comfort care, and 3% were unsure. None of the subjects switched from a less intensive to a more intensive level of care and 98% said they found the video “very helpful” or “somewhat helpful.”

When we focused on the 30 African American patients and the 30 Latino patients in our study (we intentionally recruited our sample so as to ensure that ½ would be white, ¼ black, and ¼ Latino), the results were even more striking. After being exposed only to the verbal description of advanced dementia, more blacks and Latinos than whites favored life-prolonging care. In fact, race/ethnicity—along with education—was the best predictor of whether a person would select more aggressive care. After watching the video, there was no longer any association between the level of care chosen and either race/ethnicity or education.

This was a small study conducted entirely in the greater Boston area. We don’t know whether our results would hold up if we carried it out in other locations and if we tested our video on a large and more diverse group of African Americans and Latinos. But we have reason to believe that part of what is going on when we ask patients to imagine future health states and to tell us what treatments they would or would not want is that we are failing to adequately capture what it would be like to have a hypothetical condition. We suspect that blacks, whites, and Hispanics often have a shared conception of what constitutes appropriate care—but we may need a medium such as video to better explain unfamiliar clinical situations.

Alzheimer's Toll Reaches 5 Million

A new report released by the Alzheimer’s Association brings some bad news: an estimated 5.1 million Americans currently have Alzheimer’s disease (“Alzheimer’s Disease Facts and Figures 2007,” available at http://www.alz.org/national/documents/Report_2007FactsAndFigures.pdf.) And the problem is likely to get worse. By 2050, the number of people over age 65 with Alzheimer’s will have more than doubled, rising to at least 11 million. In a press release put out by the Alzheimer’s Association, the organization’s president issued a call to action: “We must make the fight against Alzheimer’s a national priority before it’s too late. The absence of effective disease modifying drugs, coupled with an aging population, make Alzheimer’s the health care crisis of the 21st century” (Alzheimer’s Association News Release, 3/20/07, available at www.alz.org/media_7362.asp). He’s right: we need to turn our attention to this devastating disease, both by looking for treatments and by finding better ways to care for afflicted individuals. But there’s something else we can do now which would improve the quality of life for those with Alzheimer’s—and simultaneously decrease the cost of their care. The media’s response to the Alzheimer’s Association report is to clamor for more research—which is a fine idea as far as it goes, but it fails to acknowledge that no progressive neurologic disease has yet been cured, not Parkinson’s disease, not stroke, not multiple sclerosis. What we can do today is to provide more hospice care and less intensive hospital care to people with Alzheimer’s disease.

The report presents a striking graph showing that the average amount spent by Medicare on people with dementia (both Alzheimer’s disease and other types) was almost three times what Medicare spent on other patients: $13,207/year compared to $4,454/year. A small fraction of the total is spent on home health aides, but an enormous proportion is spent on hospital care and on nursing home care: the cost of hospital care for the patient with dementia is 3.2 times higher for a patient with dementia than for other Medicare patients ($7,074/person compared to $2,204/person) and the cost of skilled nursing home care is more than ten times higher for a patient with dementia ($2,144/person compared to $210/person), where skilled nursing home care translates into care in a subacute or rehab unit after hospitalization. Medicare pays only for this kind of “skilled nursing facility,” not for custodial long-term care.

By contrast, only a very small percentage of people who die of advanced dementia receive hospice care. One recent study found that a mere 5.7% of nursing home residents and 10.7% of people with dementia living at home were referred to hospice even when they were dying of their dementia (SL Mitchell, JN Morris, PS Park and BE Fries, “Terminal Care for Persons with Advanced Dementia in the Nursing Home and Home Care Settings,” Journal of Palliative Medicine (2004); 7:808-16.

Taken together, these observations about the medical care we give people with dementia paint a disturbing picture. Instead of proving comfort care to people who are at the end of their lives, who no longer can get dressed or go to the bathroom by themselves, and who can no longer carry on a conversation, we are sending them to the hospital and subjecting them to invasive and costly tests and treatments that they cannot understand. If they survive the hospitalization, we send them to a rehabilitation facility because they are often too debilitated after their acute hospital stay to return to the same nursing home or home environment from which they came.

Most older people, when asked, say that if they developed Alzheimer’s disease they would not want invasive and painful medical care intended to prolong their lives, treatment that would simply allow them to develop even more advanced dementia. But once they lose the ability to make decisions for themselves, we routinely subject them to precisely the kind of medical treatment that most of them would not want.

We can do something about this travesty today. We can talk to healthy older people about their preferences for care and document their wishes in an advance directive. It’s not unreasonable to ask patients, well before they show any signs of cognitive impairment, to think about the general approach to medical care they would favor if they turn out to be among the 42% of people over 85 who will develop dementia. We can also establish standards for what constitutes appropriate care for people with dementia, standards that would determine just what physicians recommend to patients and families. Searching for a cure is a noble undertaking and we should pursue it wholeheartedly, but as long as millions of Americans continue to contract Alzheimer’s disease, we have a responsibility to provide humane and appropriate medical care for all who suffer from this tragic condition.

Recent Interview

An interview from Ruth Dempsey at Aging Horizons:

Ruth Dempsey: In The Denial of Aging, you argue: "Despite my vitamin and exercise regimens, I am likely one day to find myself sick or frail. Better I come to terms with this reality now." Why is this message important?

Muriel Gillick: I worry that if we deny the realities of old age we will squander our resources on ineffective but costly screening tests. We will waste our resources on ultimately futile but expensive treatment near the end of life, leaving us insufficient funds for a beneficial cure.

I am concerned that if we assume Alzheimer's disease will be cured and disability abolished in the near future, we will have no incentive to develop long term care facilities that focus on enabling residents to lead satisfying lives despite their disabilities.

And I'm afraid that if we assume diet and exercise will prevent chronic disease, we will fail to look for better models of care for chronic disease. We will not bother to overhaul our medical system so that it provides incentives to physicians and hospitals to improve the care of chronic illness.

RD: You emphasize evidence-based medicine. What is it, and how is it likely to affect me?

MG: Evidenced-based medicine is an approach to medical care that rests on scientific studies. Instead of simply assuming that tests or treatments will produce the desired result, we don't prescribe those interventions unless we have sound evidence that they work.

If your physician adheres to these precepts, he or she will not prescribe something for you without good data indicating that it makes sense. This means that you will not get treatments you may read about in the popular press that sound like a good idea but have not been tested. It means you will not be subjected to treatments that are useless but have worrisome side effects. It also means that what seems desirable treatment one year may turn out not to be advisable the following year when there is new data.

RD: You recommend a brand of intermediate care for frail older people. Can you give me an example? Why is this type of care important?

MG: Many people - including physicians - tend to think that there are only two approaches to medical care: maximally aggressive treatment (whatever devices, drugs, or operations are relevant for your condition) or hospice type care, care that is focused exclusively on comfort. In fact, there are often options in between these two extremes.

A frail older person with a heart attack might be perfectly willing to have a cardiac stent placed to keep his narrowed coronary artery open (a procedure done while you are awake and requiring typically a day or two in the hospital), but not willing to undergo open heart surgery, a riskier procedure with a longer recovery period.

It's important to consider such options so as to avoid over-treatment, which often results in side effects and complications that you might strenuously wish to avoid, and also to avoid under-treatment - being deprived of potentially life-prolonging or quality of life enhancing therapy.

RD: Making end-of-life decisions can be complicated for both patient and family. Can you give me some guidelines?

MG: It's critical to have open conversations with your family members and your physician about your overall goals. You may not know whether or in what circumstances you might want to have cardiopulmonary resuscitation or be on a ventilator. But you may be able to talk about what is important to you - is it living as long as possible, no matter what? Is it retaining whatever independence you have in areas such as walking, hearing, and seeing? Or is it just being as comfortable as possible?

Explain your views to your family and your physician, who can then help translate these goals into practice. Also choose one person to speak for you - to be your surrogate or health care proxy - in case you are too sick to speak for yourself.

RD: In the book, Ruth Schatz, 93, is suffering from dementia. She is also stuck with a high-powered defibrillator that keeps going off. What can be done?

MG: Whenever an older person develops a new medical problem, it's important to think about how to address that problem in the context of the whole person, not just his heart or his kidney or whatever is failing right now. A person who develops heart problems and has progressive dementia may warrant a very different approach from a vigorous older person with the same heart problem. Typically primary care physicians or geriatricians are better at dealing with this sort of issue than specialists.

It's also important to review the overall situation periodically - drugs or devices that make sense for someone at a particular point in time may no longer make sense later. They should be discontinued or turned off if they are no longer serving the original purpose.

RD: You consider community essential for a good old age. Will you please elaborate?

MG: One of the greatest challenges in dealing with older individuals is to help them find meaning in their lives. Typically they are finished with child-rearing and have retired from their occupations. They may simply feel superannuated.

The ways most people find meaning are through participation in something larger than themselves, in their community. They need to find ways to give to that community, whether it's through tutoring elementary school children or providing advice to out-of-work executives or teaching English as a foreign language to new immigrants.

But for older people to find such opportunities, the community needs to make them available. Transportation for older individuals will have to be provided. Part-time work needs to be acceptable. Only if society recognizes its responsibility towards the elderly will the elderly be able to give to the surrounding society.

RD: You say, "A good old age is within our grasp. But we must reach in the right direction." Can you please explain?

MG: There are three or four things to keep in mind.

First, we need to change our personal behaviour. I said we shouldn't put our faith in exercise, but that doesn't mean we shouldn't do what little we can to stay limber. Exercise markedly decreases risk of heart disease, the leading cause of death in people over 65. Exercise can help prevent obesity, increasingly recognized as epidemic. And people who stay fit tend to stay self-sufficient. They can carry groceries and go up the stairs.

We should keep moving but probably shouldn't make so many geographic moves.

Cultivating relationships with family and friends mitigates against loneliness. It also has effects on health - social contacts influence the rate of recovery from a heart attack, a stroke, or a hip fracture. Finally, social engagement can help delay the onset of dementia and minimize its impact.

Second, in the realm of preventive medicine, we need to stop obsessing about things that no longer matter, resisting the impulse to request Pap smears and prostate specific antigen tests, and start paying attention to new areas that do matter. Falling and breaking a hip presents a far greater threat to independence and happiness at age 85 than does cervical cancer. We also need to consider intermediate care not just aggressive care or hospice.

Also, it's important to give people tools to help them change their behaviour. For example, we need to have some kind of continuing health education for older people. We may need prolific peddling points to encourage exercise - something like frequent flyer miles. We could have password protected sign-in sites with exercise bikes. At approved weigh-in centres, we could get points for achieving exercise and weight goals that could be used toward purchase of medications or other medical services not covered by insurance.

Third, institutional changes are also imperative. Nursing homes need to be more resident-centered. There are models of care that let residents decide when they will get up, what they will do.

As well, assisted-living facilities have to allow for negotiated risk. Diabetics may not want tight control of their blood sugar if it means forgoing the few pleasures in their lives. The facility shouldn't be penalized for serving sweets, provided residents have a choice and make an informed decision. A wobbly person may not want to use a walker, even if she risks falling. Again, the facility shouldn't be penalized for falls, provided residents are offered physical therapy, encouraged to use walkers, and they declined based on understanding of risks and benefits.

In the Grey Zone

When I went to medical school, the condition “mild cognitive impairment” had not been recognized. Patients either had dementia (which was often referred to as “senility” or “senile dementia” or “senile dementia of the Alzheimer’s type”) or they didn’t. Now we believe that dementia may be twenty years in the making. This makes a lot of sense for Alzheimer’s disease, the most common form of dementia, because Alzheimer’s is due to the abnormal deposition of a normally occurring protein called beta amyloid. If too much beta amyloid accumulates in the brain—and it tends to build up in the part of the brain particularly involved in memory, the hippocampus—the result is amyloid plaques. These plaques are something like dental plaque, but unfortunately there is no easy way to get rid of them. They can’t just be scraped off. In fact, Alzheimer’s disease may result from an imbalance between the deposition of amyloid and its removal. It takes a good long time for enough plaque to build up to result in the problems with memory, thinking, and behavior that constitute Alzheimer’s disease. So it’s not surprising that somewhere along the line, as the process develops, a person might have enough beta amyloid to experience mild memory loss without having enough amyloid to meet the criteria for dementia.

Mild cognitive impairment, or MCI, has been a hot topic of research. Clinicians have tried to define just exactly what MCI is. They have sought to distinguish it from “age-associated memory impairment,” the very slight degree of memory loss that is typically found when comparing old people (especially very old people) to young adults. MCI is now defined as a condition in which patients or families report memory problems which are not sufficient to interferer with daily life. (See R. Petersen, J. Stevens, M. Ganguli et al, “Practice Parameter: Early Detection of Dementia: Mild Cognitive Impairment,” Neurology 2001; 56: 1133.)

Researchers have also tried to figure out whether everyone with MCI is destined to develop dementia. Studies have varied in their findings, but the rate of progression to dementia is somewhere between 6 and 25% per year. Finally, investigators have studied whether any interventions can prevent the development of full blown dementia in people with MCI. One study evaluated the use of Vitamin E and of Donepezil (Aricept), two drugs that are used in the treatment of Alzheimer’s. Unfortunately, Vitamin E had no effect. Donepezil was associated with a lower rate of progression to Alzheimer’s in the first year of treatment, but not subsequently. (See R. Petersen, R. Thomas, M. Grundman et al: “Vitamin E and Donepezil for the Treatment of Mild Cognitive Impairment,” New England Journal of Medicine 2005; 352: 2379.)

How should physicians approach patients with MCI? What should families do? What should patients do if they are given this intimidating diagnosis? Right now there is no reliable way to predict who will go on to develop dementia. Magnetic Resonance Imaging (MRI) is a promising technology: patients with degeneration in the hippocampus are at risk of progression to Alzheimer’s. So too are patients with abnormal metabolism in the temporal lobe as measured on a Positron Emission Tomography (PET) scan. But these tests cannot determine with certainty who will progress and who will not. (See K. Blennow, M. de Leon, H. Zetterberg, “Alzheimer’s Disease,” The Lancet 2006; 368: 387.) Until we have treatment that will effectively prevent MCI from progressing, there is little point in trying to predict who is going to get the disease. Patients with MCI should be evaluated regularly, however, to see if they have developed Alzheimer’s or another form of dementia. At that point, treatment may be beneficial. In the mean time, patients with MCI should be sure to appoint a health care proxy to make decisions for them if they lose the capacity to make decisions themselves. And they should take the opportunity to tell their proxy what matters to them—just in case.

Alzheimer’s Centennial

On November 6, 1906, Alois Alzheimer presented a paper to his medical colleagues describing a patient, Auguste D, who had a progressive, ultimately fatal form of dementia. He studied her brain tissue under the microscope after she died, describing the tangles and plaques that would become the hallmarks of the disease. Her illness, which he distinguished from the “senility” found so often in elderly patients—Auguste D was only 51—would become known as Alzheimer’s disease.

It would take more than half a century until we recognized that “senile dementia” and “Alzheimer’s disease” were one and the same. Most people who develop this dread condition, marked by cognitive changes (memory loss being the earliest and most striking example), behavioral changes (agitation and often paranoia), and ultimately, total dependence on others for the most basic functions of daily life, are in their seventies or eighties. Less commonly, they develop the same symptoms at a much younger age. Often these individuals have a hereditary form of the disease—but it is fundamentally exactly the same disorder.

How much progress have we made in understanding and treating Alzheimer’s disease in the past 100 years? An article in the British periodical, The Lancet, (Konrad Maurer, Ian McKeith, Jeffrey Cummings et al, “Has the Management of Alzheimer’s Disease Changed Over the Past 100 Years?” Lancet 2006; 368: 1619-1621) argues that many of the basic approaches to care remain unchanged, though the number of available medications has increased enormously. The authors indicate that already a century ago, Alzheimer understood that a key element of care was the environment. Patients with dementia need calm and compassionate caregivers and an atmosphere that is distracting but not excessively stimulating.

But what about all those medications we use today—Donezpezil (Aricept) and Memantine (Namenda) and drugs such as Risperidone (Risperdal) and Olanzapine (Zyprexa)? Just how much better are they than the small doses of alcohol and sedatives such as chloral hydrate and paraldehyde that were used in Alois Alzheimer’s day? Today’s pharmacologic agents may have fewer side effects than their predecessors, certainly an important consideration, but they are far from benign—the antipsychotics, for example, have been associated with an increased risk of stroke.

What concerns me is that the effectiveness of the medications we routinely and liberally use in Alzheimer’s disease is regrettably only modest. The cholinesterase inhibitors (such as Aricept) result in a statistically significant improvement in measures of global function—but it’s far from clear that they make a real difference in the daily lives of most patients and their caregivers. A review of all studies on these drugs by the British National Institute for Health and Clinical Excellence concluded the evidence for real benefit was so questionable that they should not be considered the standard of care (see my blog posting, “Americans, Alzheimer’s, and Aricept..”) The antipsychotic drug that are commonly used for agitation, restlessness, paranoia and other major behavioral features of Alzheimer’s have just been examined at in the most sophisticated and careful study to date. Unfortunately, the conclusion of this study is that these medicines are usually no more effective than placebo (See Lois Schneider, Pierre Tariot, Karen Dagerman et al, “Effectiveness of Atypical Antipsychotic Drugs in Patients with Alzheimer’s Disease,” New England Journal of Medicine 2006; 355:1525-1538). And the glutamatergic antagonists (ie Memantine) have been shown to slow the progression of disease in patients whose dementia is already advanced—an effect which some might regard as tantamount to leaving patients suspended in a condition worse than death. (See Barry Reisenberg, Rachelle Doody, Albrecht Stoffler et al, “Memantine in Moderate-to-Severe Alzheimer’s Disease,” New England Journal of Medicine 2003; 343:1333-41).

Scientists have made remarkable strides in understanding the genetic and biochemical underpinnings of Alzheimer’s disease. Several promising avenues of research into treatment are being vigorously pursued—a vaccine, tested in mice, has led to dramatic regression of plaques in the brain. But bran diseases are extraordinarily complicated and those affecting thinking are particularly recalcitrant to treatment. Perhaps we should spend as much effort on designing more humane environments in which to care for people with dementia as we do searching for a pharmacologic fix.

A Time to Be Born, A Time to Die

On September 6, the Food and Drug Administration (FDA) approved the use of the artificial heart. The AbioCor heart, the device that was approved, has been used in 14 people. Their experience formed the basis of the FDA decision. All 14 had very advanced heart failure at the time of the surgery, so advanced they were not expected to live for more than a month. They could scarcely walk without getting short of breath and they were not candidates for a heart transplant (typically because of their age or other medical conditions). All 14 have died: 2 died during surgery, and 6 of the survivors suffered strokes. They lived an average of 5.2 months with the surgery, including one subject who lived for 17 months. However, only one was discharged home. Ten left the hospital only with short passes, and 1 moved to a hotel near the hospital. The cost of the device has been set at $250,000 by AbioMed, its manufacturer. The hospital charge for the insertion (not counting the cost of the prolonged hospital stays that have been required to date) is estimated at $100,000.

A little over a year ago, the scientific advisory panel to the FDA recommended against approving the device. FDA approval is contingent on a device being “safe and effective.” The artificial heart was deemed “effective,” since it prolonged life from an expected one month to an average of 5.2 months. The advisory panel, by a 7:6 vote, concluded they could not consider a device which led to major strokes in 50% of the recipients and which kept almost all patients hospitalized until their deaths “safe.” Usually, the FDA heeds the recommendation of its advisory panel. In this instance, without any engineering modifications since the advisory panel met in June, 2005, the FDA nonetheless approved the device. What happened?

The story of just who put pressure on whom to win approval of the device has yet to be researched. Interestingly, back in 1976, the director of the National Heart, Lung and Blood Institute tried to pull its contracts with 4 firms for designing and manufacturing the total artificial heart on the grounds that the technology was too flawed and too expensive. He didn’t expect anticipate the response from 2 powerful senators, Orrin Hatch of Utah and Edward Kennedy of Massachusetts, in whose states several of the firms were based. At their insistence, the contracts were reinstated—including the one to Abiomed, the Danvers, Massachusetts firm that produces today’s AbioCor heart. (For further insights on the history of the AbioCor heart, see the article by Renee Fox and Judith Swazey, “He Knows That Machine is His Mortality: Old and New Social and Cultural Patterns in the Clinical Trial of the AbioCor Artificial Heart,” Perspectives in Biology and Medicine 2004; 47:74-93).

What we know today is that the FDA decided not to grant full approval, but to allow use of the device under its “humanitarian exception” provision.” The standard in these cases is that the device be “safe and probably beneficial” and that the condition for which it is used afflicts fewer than 4000 individuals per year. The FDA, to be fair, has a tough job. It has to weigh the risks and the benefits of a new device. It has no clear calculus for doing this. In clinical practice, we typically offer treatments that “work” and expect patients to figure out, using their own personal values, whether the potential advantages of the treatment outweigh the disadvantages. When the treatment (whether drug or device) simply doesn’t do what it’s supposed to do, the job is fairly easy. When it does what it’s alleged to do, but there’s a safer alternative, the job of deciding on approval is also fairly straightforward. In the case of the artificial heart, it seems to “work,” if we define working as, on average, prolonging life. But the cost to the individual is enormous. Tom Christenson, the one subject who lived for 18 months after the implant, developed a fever to 107, kidney and liver failure and respiratory problems. He actually made it home for a few months, only to be readmitted to the hospital at which point the decision was made to disconnect the power source of the device and allow him to die.

Just because the FDA has approved use of the device doesn’t mean that it will automatically be paid for by the major health insurers. Medicare, for instance, has a process for making coverage decisions for controversial technologies such as the artificial heart. Medicare is required by law to make available to enrollees in the Medicare program any medical intervention that is “reasonable and necessary,” a phrase even less well-defined than the FDA’s “safe and effective.” Officially, Medicare is not supposed to take cost into consideration. This has become increasingly problematic as more and more expensive and only marginally useful procedures have entered medical practice, such as lung volume reduction surgery (an operation in which parts of the lung are cut out of patients with emphysema), the implantable defibrillator (a device that automatically shocks the heart if it detects a potentially dangerous heart rhythm), and the left ventricular assist device (another device used for patients suffering from very advanced heart failure, one that boosts the function of the heart rather than replacing the heart entirely). As a result, the Centers for Medicare and Medicaid Services has begun setting the price it will pay for certain procedures far below their actual cost—the left ventricular assist device was initially reimbursed at $70,000 even though the device alone cost $65,000 and the surgery to insert it typically cost over $200,000. With the AbioCor Heart, if Medicare does agree to cover the device, it will no doubt employ a similar strategy: it will choose to permit use of the device but pay something like $150,000—roughly what it pays for a heart transplant but less than half the cost of the new procedure—a strategy that will no doubt put a crimp on actual use of the procedure. (See my article, “Medicare Coverage for Technological Intervention: Time for New Criteria? Published in the New England Journal of Medicine 2004; 350: 199-203).

Replacing the human heart has been the American dream since the National Institutes of Health established an Artificial Heart Program in 1965. Originally granted $600,000 and 5 years to achieve its goal, the project has continued for over 40 years. Along the way, it has been critically reviewed multiple times, sometimes with the recommendation that the work continue only if the technology is expected to be cost-effective, or a good “value for the money.” At $350,000 to implant the AbioCor heart—and this figure does not take into account the full cost of hospitalization for these patients (all but 2 of the initial 14 cases spent the rest of their lives in the hospital)—it is surely not a good value. Heart disease is a critically important problem in America, afflicting some 5 million people. Perhaps it’s time to focus on preventing this disease—which we can do, if we do a better job on the prevention of high blood pressure, diabetes, and cigarette smoking. For those patients who do develop heart failure and who are dying of their heart failure, palliative care is an excellent means of addressing their symptoms and supporting them and their families in their final days.