The Skinny on Longevity

It’s been known for some time that skinny rats live longer than fat rats. They have to be extremely svelte for this effect to kick in: laboratory rats that consume 60% of the usual rat diet live 30% longer than the average rat. Studies are underway in primates, but because monkeys live for many years, the results of “caloric restriction,” as the intervention is called, on their longevity is not yet know. But a new study in the Journal of the American Medical Association suggests that a comparable phenomenon is at work in people.

A team of researchers from Louisiana State University in Baton Rouge and the Garvan Institute for Medical Research in Darlinghurst, Australia reported on a randomized study involving 48 people (see Leonie Heilbron, Lilian de Jonge, Madlyn Frisard et al, “Effect of 6-Month Calorie Restriction in Biomarkers of Longevity, Metabolic Adaptation, and Oxidative Stress in Overweight Individuals,” Journal of the American Medical Association 2006; 295:1539-48). The 48 people included men under 50 and women under 45 who were healthy but sedentary and overweight but not obese. It was hard to find people to participate: of 599 people who were screened for participation, 460 failed to meet the criteria. Another 91 people decided as they were being screened that they weren’t interested in participating. For the 48 people who did enroll, 12 served as controls and were kept on a weight-maintenance diet; 12 were assigned to a calorie restricted diet (25% restriction of their baseline energy requirements); 12 were assigned to a combination of calorie restriction and exercise (12.5% calorie restriction and 12.5% increase in energy expenditure through exercise); and 12 were assigned to a very low calorie group (890 kcal/day). Midway through the study and then at the end of the 6-month study period, all sorts of measurements were performed, including tests reflecting metabolism, tests of DNA damage, and of course weight.

What the authors found was that after six months of the prescribed regime, insulin levels and core body temperature were decreased in the intervention groups, both of which are “biomarkers of longevity.” They also found evidence of “metabolic adaptations,” i.e. lower energy expenditure in the groups on the special diets. While they could not conclude anything about whether these changes would persist if the subjects continued on their diets indefinitely and they certainly could not conclude that the subjects would live longer if they kept up the diet, they found the results “suggestive.”

The interesting aspect of this work is the possibility not that we could live longer if we starved ourselves, but rather that the aging process might be slowed down if we could find ways to emulate the effects of caloric restriction. Nobody seriously believes that large numbers of people are going to go on an 890 calorie diet indefinitely in a society where we cannot even find ways to prevent obesity or to help markedly overweight individuals lose weight. Most people aren’t really interested in living to be 100, particularly not if it means a long period of physical frailty and cognitive impairment. But if scientists could design chemicals that mimic the effects of calorie restriction and if these chemicals are able to delay aging, then conceivably all the major disorders of old age—heart disease, cancer, dementia—would have a later age of onset.

Of course it’s far from clear from a study of 48 people conducted over a mere 6 months that caloric restriction will have the desired age-delaying effect. And even if caloric restriction does prove effective, it will be a long way to finding a pill that produces the desirable consequences of caloric restriction without any significant side effects.

Before any older individuals cut down on food in the hope of preventing disability, it’s critically important to note that among older people today, malnutrition rather than obesity is a major problem. In the National Health and Nutrition Examination Survey, a study conducted periodically by the federal government, the incidence of malnutrition is reported to range between 12 and 50% among hospitalized older people and from 23-60% among institutionalized older adults. In the community, where malnutrition rates are lower, it remains a problem among people with low income, difficulty digesting or chewing food, and people who have trouble shopping or cooking (See Carol Evans, “Malnutrition in the Elderly: A Multifactorial Failure to Thrive,” Permanente Journal 2005; 9:3).

Facing our mortality is not easy. But phantasmagorical dreams of perpetual life are not the answer. What I argue in my book, The Denial of Aging: Perpetual Youth, Eternal Life, and Other Dangerous Fantasies is that immortality projects are better ways to cope with knowledge of our finitude than are searches for the elixir of life. Immortality projects—whether a book we write, a company we found, or the children we nurture—help us transform our painful awareness of our own limits into enduring memories. They are the way we leave a mark on the world, even after we ourselves have departed.

Newsweek Interview

Here's an interview Newsweek did a few days ago.

Adding Life to Years

The latest statistics on life expectancy were released by the National Center for Health Statistics in January, 2006 and they show continued improvement in the prospects for old age (DL Hoyert, M. Heron, SL Murphy, and HJ Kung, “Deaths: Final Data for 2003,” National Vital Statistics Reports. National Center for Health Statistics, Hyattsville, MD, released January 19, 2006). Life-expectancy at birth is 77.5 years, as of 2003, the year on which the results are based, surpassing the previous record, from 2002, by 0.2 years. The age-adjusted death rate (that is, the death rate taking into consideration the distribution of ages in the population) is also at a record low, down 1.5% from 2002.

If we examine the statistics more closely, we discover several interesting observations. First, let’s look at life expectancy at age 65. Life-expectancy at birth reflects the risk of dying of congenital abnormalities or of the dangers that affect young adults, such as AIDS and homicide. For older people, what is of concern is how much time they are likely to have left if they have made it through middle age. The answer is that life-expectancy at age 65 is an impressive 18.4 years. It is even higher for white women (19.8 years) and a little lower for white men (16.9 years). What is disturbing, however, is how much lower life-expectancy at age 65 is for black men (14.9 years). Black women, by contrast, are just about exactly at the national average (18.5 years).

Since age 65 really is not considered “old” any more, what is of even greater interest is the data on life-expectancy at age 75. The 2003 data indicate that 75-year olds can expect, on average, to live for another 11.8 years. Again, the situation is a little better for white women (12.6 years) and a little worse for white men (10.5 years). And again, the life-expectancy for black men is unfortunately only 9.7 years, although black women are almost as well off as white women, in terms of years of life left (12.4 years compared to 12.6 years).

Another important result reported by the government is that while the age-adjusted death rate is down for several of the leading causes of death, including heart disease, cancer, and stroke, the rate of Alzheimer’s disease continues to rise. Regrettably, this means that as we make strides in the treatment of many of the diseases afflicting the elderly, the net result is often that people live long enough to develop and ultimately die of dementia.

What is not discussed in the government statistics is the rate of chronic disability in old age. While we all aspire to live longer, for many of us it is critical that those additional years be good ones. We want to live longer but we want to be as independent as possible. We don’t want to require the help of others for our most basic activities—dressing, bathing, eating, walking. It turns out that the studies that have been done analyzing disability rates show that from 1982 to 1999 (no more recent figures are available for the U.S.) disability declined: one report calculates that the decline from 1982 to 1989 was 0.26% per year, the decline from 1989 to 1994 was 0.38% per year, and the decline from 1994 to 1999 was 0.56% per year (Kenneth Manton and XiLiang Gu, “Changes in the Prevalence of Chronic Disability in the United States Black and Nonblack Population Above Age 65 from 1982 to 1999,” Proceedings of the National Academy of Science (2001); 98: 6354-6359). A second report, summarizing the results of various other studies, suggests that the rate of decline in disability among the elderly has been 1% per year for several decades (David Cutler, “Declining Disability Among the Elderly,” Health Affairs (2001); 20: 11-27).

But if we examine the data on chronic disability carefully, what we find is that the improvements are most pronounced for domains such as the ability to cook or shop or clean house. The fraction of the elderly population with severe disability remains virtually unchanged. Moreover, historical research indicates that it is hazardous to predict future rates of decline based on recent trends: in the past, sharp declines in disability rates have often been followed by stability or increases in disability. (See: Donald Redfoot and Sheel Pandya, “Before the Boom: Trends in Long-Term Supportive Services for Older Americans with Disabilities,” AARP Policy Institute, October, 2002.) Recent work on the potential long term outcome of the obesity epidemic, for example, predicts that even the gains in life expectancy may be reversed (see S. Jay Olshansky, Douglas Passaro, Ronald Hershow et al, “A Potential Decline in Life Expectancy in the United states in the 21^st Century,” New England Journal of Medicine; 2005; 352: 1188-95).

What should we conclude from all of this? We can conclude that most of us who reach retirement age will live past 80. During much of our old age, we will be quite vigorous. But we are still at considerable risk for developing frailty (severe physical disability) and dementia (cognitive disability). Preventing these conditions, treating these conditions, and developing supportive care that will enable us to make the most of our old age despite these conditions, are the challenges that lie ahead.

Break a Leg?

Sometimes I wonder what disease will get me in the end: statistically speaking, it’s a toss up between cancer and heart disease. But I worry even more about breaking a hip. For many older people, a hip fracture is the beginning of the end. After sustaining a hip fracture, only 50-60% of people walk as well as they did previously. About 20% never walk again and 40% end up in a nursing home. Within a year, 37% of elderly Americans who break a hip are dead.

Not only are your odds of returning to your baseline level of functioning poor, but the chance of breaking a hip is substantial: 350,000 Americans break a hip each year. Older people are at risk of fractures because they fall and because they have thin (osteoporotic) bones. So articles in two major medical journals in the last month that call into question the efficacy of two leading preventive strategies—calcium and vitamin D on the one hand and hip protector pads on the other—are worrisome. Should all older people give up their calcium supplements and forget about wearing hip pads?

The study of calcium and vitamin D appeared in the New England Journal of Medicine (R. Jackson, A. Lacroix, M. Gass et al, “Calcium Plus Vitamin D Supplements and the Risk of Fractures,” NEJM 2006; 354:669-83). The authors had the opportunity to randomize over 36,000 women who had previously enrolled in a Women’s Health Initiative trial to receive either 1000 mg of calcium carbonate and 400 units of vitamin D or placebo. They were monitored for fractures for the next 7 years and their bone density was measured. The results? There was a small but not statistically significant decrease in the risk of hip fracture, a small improvement in bone density, and a small increased risk of kidney stones.

Before throwing away those calcium and vitamin D pills, it’s important to realize that only 59% of the women were actually taking the recommended dose at the end of the study. When the authors evaluated the outcomes in women who really took the medicine, there was a 29% statistically significant decrease in the likelihood of hip fracture. For scientific reasons, the analysis should be done the way the authors did it—using an “intent to treat” approach. This allows them to conclude that from a public health or policy perspective, they cannot recommend the use of calcium and vitamin D because prescribing those supplements is not likely to produce the desired outcome. But that’s different from concluding that taking the medication will not result in lowering your chance of hip fracture. It’s also important to realize that the 36,000 women in the study were healthy, community-dwelling post-menopausal women with an average age of 62. Inferring from this study that calcium and vitamin D do not prevent hip fractures in older women with other medical problems is not warranted. And in fact there was some suggestion that women over 60 did in fact benefit.

The second study on a related subject was a meta-analysis or pooled analysis of previous studies that was published in the British Medical Journal. (M. Parker, W. Gillespie and R. Gillespie, “Effectiveness of Hip Protection for Preventing Hip Fractures in Elderly People: Systematic Review,” BMJ 2006; 332: 571-4). It asked whether hip pads achieved their initial promise: earlier studies of nursing home patients had found that hip protectors could halve the rate of hip fractures. After combining the information from 14 studies, 11 of which involved nursing home patients and 3 of which were conducted in community-dwellers, the authors were unimpressed. They concluded that the pads were ineffective in the home setting and conferred only a small (but statistically significant) benefit in institutionalized individuals. But very much like the work on calcium, it turns out that many of the people who were supposed to wear the hip pads didn’t do so for much of the time. They found them inconvenient or awkward or uncomfortable, despite efforts to streamline the pads. Once again, it’s reasonable to conclude that hip pads should not at this point be the “standard of care.” We shouldn’t routinely expect insurance companies to pay for them or nursing homes to provide them. But there may well be a benefit for the person who is at high risk of falls and fractures and who is motivated to use them.

The data aren’t all in yet—we may find that calcium and vitamin D are effective, but higher doses are required, or it may turn out they are principally useful in an as yet undefined subgroup of the population. We may discover that certain types of hip protectors work and others, made of different materials, do not. In the meantime, these two interventions may make a lot of sense for people who want to do everything they can to avoid a hip fracture. And that’s not such a bad idea.

How Much will Medical Care Cost After Retirement?

Fidelity Investments just released a report estimating what the average 65-year old couple can expect to pay in medical expenses during their retirement (Reuters: “US Retirees’ Health Care to Cost $200,000-Fidelity”) Fidelity’s prediction is that a couple can anticipate spending $200,000 over the next 20 years. This is up from $190,000 in 2005 and $175,000 in 2004.

This figure—and clearly it’s just an estimate—is based on the expected cost of premiums for Medicare Part B and Medicare Part D, plus the cost of co-payments, deductibles, and out-of-pocket prescription drug costs. It does not include dental care, over-the-counter prescriptions, or long term care (ie nursing home costs).

It’s important to realize that this figure is based on the fact that the average life expectancy for a man at age 65 is 15 years and for a woman is 20 years. Actually, a 65-year old white man will, on average, live another 16.6 years; a 65 year old white woman will live 19.5 years; a 65 year old black man can expect to live another 14.6 years; and at age 65, a black woman will, on average, live for 18.3 years (see Health United States, 2005). Since these are averages, some people will live less long, and others a good deal longer.

Fidelity’s estimate assumes the couple will enroll in Medicare but have no supplementary employee health insurance coverage. Increasingly, corporations are discontinuing their medical care coverage for retirees in order to save money, so couples should not count on having such benefits. Out-of-pocket medical costs are the single largest expense for most retired couples, so start saving now!

The New Presidential Ethics Commission Report

You may never have heard of a national bioethics commission. At best, such commissions can perform a valuable synthetic function, summarizing the best current thinking on a controversial ethical topic. The 2 reports of the President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research, one on defining death and one on decisions to forgo life-sustaining treatment, did exactly that. As Alexander Morgan Capron comments in his article, “Governmental Bioethics Commissions: the Nature of the Beast,” (Lahey Clinic, Fall, 2002) these reports were successful because they “built a bridge connecting the legislative and executive branches, experts and academics in science, philosophy and law, and the general public,” resulting in the adoption of better policies. Regrettably, the current “President’s Council on Bioethics,” appointed by President George W. Bush and chaired by Dr. Leon Kass, has not served as a forum for public discussion of controversial issues, but rather as support for the president’s political agenda (for a discussion of how this problem could be remedied, see Arthur Caplan’s article, “Free the National Bioethics Commission”.)

The newest report, “Taking Care: Ethical Caregiving in Our Aging Society,” (September, 2005) has unfortunately adopted the ideological coloring of the executive branch. Taking Care is important in recognizing that one of the major challenges our society faces is how best to deal with the growing elderly population, many of whom will develop dementia. It makes the critical point that dementia in particular and frailty in general are unlikely to disappear any time soon. But the ideological driving force behind the report is the belief that euthanasia and assisted suicide are “antithetical to ethical caregiving” and “should always be opposed.” The report devotes one of its four chapters to a tirade against advance directives. The authors seem to think that the purpose of advance directives is to enable patients to decide, at the first sign of incipient frailty, to end their lives by forgoing life sustaining treatment. They envisage long lines of patients clamoring for physician assisted suicide. In fact, in Oregon, the one state where PAS is legal, a total of 33 people availed themselves of it in 2004, accounting for less than one-eighth of one percent of the deaths in that state. And advance directives, for all their flaws and limitations, have as their goal to enable prospective patients to avoid unwanted, burdensome, and often near-futile treatment near the end of life.

The report is also disturbing in its excessive focus on family caregivers. Having attacked individual autonomy as inadequate, Taking Care endorses family responsibility for the frail elderly. The relentless emphasis on individual responsibility that characterizes much of modern biomedical ethics may indeed be inadequate to address the situation of impaired elders. But surely a more communitarian vision warrants consideration—a society in which we build nursing homes and assisted living facilities that are truly resident-centered, rather than “total institutions,” a society in which we develop a system of health insurance that includes long term care and that provides excellent treatment for chronic as well as acute conditions, and in which we find ways to enable people to remain engaged and contributing citizens, even if they have problems with their hearing, their vision, their memory, or their walking. Taking Care seems to echo the party line that “family values” are paramount. Let us hope that this report receives the disregard it deserves.

The Medicare Cuts

Last week, President Bush released his proposed budget for 2007, which included $36 billion cuts in Medicare spending over 5 years. The response has been anxiety on the part of older people who worry their benefits will be slashed, as well as by hospitals and physicians who depend heavily on the Medicare population for their business. But are the cuts—if they go through, and in an election year, many will not—such a bad idea?

Medicare spending is growing at a phenomenal rate. If we don’t put the brakes on it, according to some projections, Medicare will consume 24% of all federal income tax revenue by 2019 and 51% by 2042 (quoted in “Medicare: A Ticking Time Bomb for Tax Increases” by Daniel Mitchell of the Heritage Foundation). We won’t have much left for education, housing, and other social programs (leaving aside the issue of national security). The Medicare prescription drug benefit alone, crucial as it is for the millions of elderly people who rely on medicines to treat chronic illnesses and who previously had no drug coverage, is expected to cost at least $700 billion over the next 10 years. It won’t do to protest every attempt to control Medicare spending. The question is not whether Medicare should be trimmed back, but how.

The suggested approaches in the President’s budget largely reflect the recommendations of the Medicare Payment Advisory Commissions (MedPac), an independent, bipartisan panel that has a reputation for thoughtful, careful proposals. And it’s important to realize that the budget proposal isn’t calling for lower reimbursement rates than currently prevail; it’s calling for a smaller increase than previously planned (eg payments to hospitals would increase by 2.9% rather than 3.3%). Moreover, to complement moderately increased reimbursement rates, Medicare would introduce a quality incentive payment policy for hospitals. While this has to be done carefully to make sure hospitals are not penalized for taking care of the sickest patients (if quality is defined in part by mortality rates, for example, adjustments must be made to take into consideration just how complex and elderly a hospital’s patients are), it is potentially a means of stimulating improved quality of care.

One piece of the budget that is worrisome is the freeze on prospective payment rates to home care agencies and skilled nursing facilities. Home health care has been one of the fastest growing components of the Medicare budget and is thus a logical target for cost-cutting. But a large fraction of the cost of home health care and of nursing home care is labor. And most of this labor is provided by aides, who are among the lowest paid, least appreciated workers in the US economy. The average hourly wage for a nursing home aide, as reported in 2002, was $8.29, less than what she would earn working in a fast food chain. Only 68% of home health aides receive health insurance from their employers. To make matters worse, home health aides and certified nursing assistants experience higher injury rates than workers in any other industry, including the construction industry. Lifting and turning sometimes resistant older people is literally backbreaking work. (Statistics are from Nora Super, “Who Will Be There to Care? The Growing Gap between Caregiver Supply and Demand,” a National Health Policy Forum Background Paper, issued January, 2002). To freeze payments to home health agencies and nursing homes will prevent wages from rising for their workers. As it is, we are facing an imminent shortage of long term care workers. The number of people who will need personal care (whether in a nursing home, assistant living facility, or at home) is going to soar from 8 million today to 19 million in 2050, at the same time that the working population is growing slowly. If we want to have aides to care for older people, we need to make the work more attractive—and freezing salaries at their current low rate is exactly the wrong way to proceed.

What’s striking about the proposed Medicare spending cuts is what measures aren’t included that should be. Right now, Medicare will reimburse for any medical treatment that it accepts as “reasonable and necessary.” Costs don’t figure into reimbursement decisions at all: the Centers for Medicaid and Medicare Services (CMS), which runs the Medicare program, pays for technology and now medications even if their added benefit is miniscule and their cost is enormous. As an example, Medicare will pay for the left ventricular assist device, a kind of partial artificial heart. This device is implanted in people with extremely severe heart failure who are too sick or too old to qualify for a heart transplant, at a cost of roughly $250,000. Even with the device, about half such patients are dead within a year and only a quarter are alive at the end of 2 years. People who have the device are at high risk of developing severe infections, bleeding, or device failure (which necessitates a second open heart operation). One way to rein in Medicare spending is for CMS to consider costs in its decisions about which treatments to reimburse. A well-established way of doing this is with cost-effectiveness analysis, a means of comparing the costs of alternative strategies for treating the same condition relative to their efficacy. For the left ventricular assist device, a cost-effectiveness analysis by Blue Cross/Blue Shield shows that the cost/quality-adjusted-life-year, the standard unit of measurement, is about $500,000, compared to the benchmark of $100,000/quality-adjusted-life-year for widely accepted procedures such as kidney dialysis (see the report by the Technology Evaluation Center of BC/BS, “Special Report. Cost-Effectiveness of Left-Ventricular Assist Devices as Destination Therapy for End-Stage Heart Failure,” released in April, 2004).

The Bush budget proposal starts the critically important process of controlling Medicare spending. It includes a number of reasonable strategies, and several short-sighted ones. But it misses a major opportunity, the chance to systematically build considerations of cost into the process of deciding what Medicare will cover and what it won’t.

Americans, Alzheimer’s, and Aricept

According to the drug company giant Pfizer, 2.4 million Americans have taken donepezil (Aricept) since it was approved by the Food and Drug Administration in 1996 for use in mild to moderate Alzheimer’s disease. The British think tank, NICE (National Institute for Health and Clinical Excellence), which evaluates the effectiveness of drugs and devices, reported last month that the drug’s usefulness is very limited. If it’s helpful to anyone, it’s mainly those with somewhat more advanced Alzheimer’s who stand to benefit. By contrast, the American Academy of Neurology says that “considering” Aricept is the “standard” approach for mild to moderate disease (RS Doody et al, “Practice Parameter: Management of dementia: An Evidence Based Review. Report of the Quality Standards Subcommittee of the American Academy of Neurology,” Neurology 2001; 56: 1154-66.) And the Alzheimer’s Association, the leading non-profit advocacy group in the field, while falling short of endorsing the use of Aricept and related drugs, recommends their use “if clinically indicated, to treat cognitive decline.” (California Workgroup in Guidelines for Alzheimer’s Disease Management: Alzheimer’s Association of Los Angeles, Riverside and San Bernardino Counties, 2002).

The latest dispute over anti-Alzheimer’s drugs began last March when, after performing an exhaustive review of every study published on the effect of the drugs on cognition, on daily functioning, or on behavioral symptoms, NICE issued a report concluding that neither Aricept nor its newer cousins, Rivastigmine and Galantamine, were worth the money the National Health Service (NHS) spent on them. They clearly did something—they produced a statistically significant improvement in various test scores, but the real life benefit was miniscule. When NICE released its report, family members of Alzheimer’s patients, physicians, and of course the drug manufacturers, were outraged. They were convinced, based in many cases on anecdotal experience, that the drugs worked. NICE responded by asking the drug companies to produce evidence that there were in fact subgroups of people who benefited substantially from this entire class of drugs, known as cholinesterase inhibitors.

Last month (January, 2006) NICE released a new report in which it once again asserted the drugs are of no meaningful use in people with mild Alzheimer’s. They concede there may be enough benefit in people with moderate Alzheimer’s to warrant trying them. In other words, even after bending over backwards to find some justification for recommending the use of Aricept and similar drugs in people with early Alzheimer’s, NICE just couldn’t find any.

The view that Aricept, with US sales in 2004 of just under a billion dollars, probably shouldn’t be used in most of the patients for whom it’s prescribed, has so far been largely ignored in the U.S. It hasn’t been picked by the New York Times or the Washington Post or by the news section of leading American medical journals such as the Journal of the American Medical Association. And this isn’t the first time we in America have chosen to pay little attention to fairly compelling evidence that Aricept doesn’t work well. In 2004, another British study, this one a randomized controlled clinical trial, tested whether Aricept could delay nursing home placement, a claim made in many advertisements for the drug. The study, which compared 283 patients who got Donepezil with an equal number who did not, found the two groups had exactly the same chance of admission to a nursing home (AD2000 Collaborative Group, “Long-Term Donepezil Treatment in 565 Patients with Alzheimer’s Disease: Randomised Double-Blind Trial,” Lancet 2004; 363:2105-10.) It was published in a leading journal, the Lancet, and did generate a response by the Alzheimer’s Association, journals such as the Journal of the American Geriatrics Society, and also by the New York Times, but many practicing physicians remained unaware of its existence. The study has been criticized on a variety of technical grounds. But why accept the results of earlier, small, non-randomized studies and reject the results of a much better, although less than perfect, randomized study? Only a fervent desire to believe the conclusions of the study that professed to show Aricept keeps people out of nursing homes can explain this phenomenon.

The irony is that when the cholinesterase inhibitor Tacrine was first alleged to help in Alzheimer’s disease, back in 1986, the American neurologic community was extremely skeptical. How could a drug that worked by preventing the destruction of a neurotransmitter in the brain (acetylcholine) be useful in a disease in which the nerve cells that used that neurotransmitter had already been destroyed? And the skeptics seemed justified when the experiments behind the first enthusiastic reports were found to be if not fraudulent, at least questionable. After years of further study, rigorous tests established that the drug did have a statistically significant effect. Whether it had a clinically meaningful effect was another matter.

Even when Tacrine was approved by the FDA in 1994, and then, in record time, its successor, Aricept, was also approved, many Alzheimer’s researchers were dubious that the drugs was actually helpful. John Growdon, a prominent researcher at the Massachusetts General Hospital in Boston, wrote diplomatically in an editorial in the New England Journal of Medicine that “the expectation of benefit…exceeds reality.” Yet use of cholinesterase inhibitors in the US has become more and more widespread. In 2004, Aricept was ranked #52 in the top 200 drugs by sales in the US ($.92 billion, up from a rank of 62 and sales of $0.7 billion in 2003). Why?

Alzheimer’s is perhaps the most feared disease of old age. Called “the gray plague,” it makes once vibrant people debilitated and dependent (see my book, Tangled Minds: Understanding Alzheimer’s Disease and Other Dementias; NY: Dutton, 1998). It’s not surprising that family members of those afflicted are desperate for a treatment. It’s not surprising that physicians are eager to have something to offer—and one after another, the various proposed remedies have proved worthless or even harmful, including estrogen and Rofecoxib (Vioxx). But should we be spending nearly a billion dollars a year to indulge our wishful thinking? Or would we all be better off spending the billion dollars on research for other drugs which might actually be effective? Or perhaps we could invest the billion dollars in improving the quality of nursing homes and assisted living facilities that claim to specialize in the care of people with Alzheimer’s so as to find ways to promote dignity and well-being in some of our most vulnerable and most demeaned citizens. The British seem to recognize that an unchecked appetite for drugs that might be beneficial has consequences when our resources are unlimited. Americans are loath to accept this view. Maybe we have something to learn from our English cousins.

Does Exercise Prevent Dementia?

We would all like to believe that if only we eat well and exercise regularly, we will remain vigorous well into our eighties and perhaps our nineties. But is it true? A new study published this week argues that exercise can help fend off dementia, one of the major plagues of old age.

Writing in the Annals of Internal Medicine, a leading medical journal, Dr. Eric Larson and his colleagues in Seattle, Washington, describe a study in which they monitored a group of 1740 people over age 65 for an average of 6 years to see whether they developed dementia. To be part of the study, you had to be free of any evidence of dementia. You were asked questions about your medical conditions, whether you smoked, whether you used alcohol, and whether you rated your health as excellent, very good, fair, or poor. You were also asked one question about exercise: over the past year, how many times per week did you spend at least 15 minutes on an activity such as walking, hiking, bicycling, aerobics, or swimming. All the people who agreed to be in the study were then tested for dementia twice a year. By the end of 6 years, 1185 of them were still free of dementia, 158 had been diagnosed with dementia, and another 397 either died or withdrew from the study. The authors then compared the risk of developing dementia among those who had said they exercised at least 3 times a week with the risk of developing dementia among those who said they exercised less than 3 times a week. What they found was that when they made adjustments to account for factors such as age and gender, the exercise group was 32% less likely than the low-exercise group to be diagnosed with dementia. (See Eric Larson, Li Wang, James Brown et al, “Exercise is Associated with Reduced Risk for Incident Dementia among Persons 65 Years of Age and Older,” Annals of Internal Medicine 2006; 144: 73-81).

Physical activity in both middle age and old age is a good idea for a variety of reasons. In addition to its well-known effects on preventing heart disease, the leading cause of death in older adults, exercise can prevent or at least delay the onset of frailty, a syndrome in which people typically have multiple medical problems which together cause impairments in their ability to function in their daily lives (see my book, Lifelines: Living Longer, Growing Frail, Taking Heart, NY: Norton, 2001.) Exercise can help prevent obesity, which is currently epidemic in the U.S. But it’s important to remember that while exercise can decrease the risk of a variety of conditions that afflict older people, it does not prevent them. In the study of exercise and dementia, for instance, fully two-thirds of the people who developed dementia had exercised at least 3 times a week. Among those who did not get dementia, there were more regular exercisers (77% instead of 67%), but it was hardly the case that the couch potatoes got dementia and the exercisers did not. In fact, in this study of relatively young, educated, middle class people, dementia didn’t develop very often either in exercisers (10.38%) or non-exercisers (16.4%). Among the general population over age 85, by contrast, nearly 50% have dementia.

It’s also important to realize that the new study doesn’t definitively show a causal connection between lack of exercise and dementia. Because it is an observational study and not a randomized trial—the people in the study were watched and tested rather than being assigned to either an exercise group or a sedentary group—we don’t know for sure whether it was exercise that was responsible for the difference in outcomes. The authors did their best to make statistical corrections to account for factors such as age, cigarette smoking, and alcohol use that might affect the likelihood of getting dementia. But it’s possible that people who exercised (or more precisely who said they exercised) were also more socially active or intellectually engaged and it was those behaviors that helped protect them from dementia. It’s even possible that the people who didn’t exercise were already in the early stages of dementia—so early they still did well on the tests of cognitive function they were given—and that it was the dementia that prevented them from exercising rather than the other way around.

The answer to whether you should exercise, whether you are 60, 70, or 80, is a resounding yes. But will exercise save you from dementia? Maybe, but don’t count on it.

The Supreme Court and Physician-Assisted Suicide

The good news is that the Supreme Court just ruled 6-3 that the U.S. Attorney General has no business trying to prevent Oregon from implementing its physician-assisted suicide law (Linda Greenhouse, “Justices Reject U.S. Bid to Block Assisted Suicide,” NY Times, 1/18/062006;). Regardless of what you think about the appropriateness of physician-assisted suicide—and I think there are better ways to address end-of-life suffering—you should be glad that the Court has upheld Oregon’s law. The Supreme Court already concluded 8 years ago that there is no constitutional right to physician-assisted suicide, but neither is there any constitutional prohibition of the practice. States were held to be free to pass legislation legalizing physician-assisted suicide if they wished.

State legislatures haven’t exactly jumped at the opportunity to pass such legislation. To date, only Oregon has a “death with dignity” law. And very few individuals have taken the steps outlined by the law to obtain prescriptions for medication they could use to end their lives (only 326 people between 1997 and 2004). Even fewer actually took the medication (only 208)—most died of their underlying disease and just wanted the medication as an insurance policy. There are even some suggestions that the availability of physician assisted suicide in Oregon led to improved palliative care and more referrals to hospice as physicians developed a heightened awareness of the inadequacies of end-of-life care. Instead of choosing to end their lives as a response to their physical or psychic distress, patients have enhanced access to programs that ameliorate symptoms and provide support to both patients and families.

Former Attorney General Ashcroft did not approve of physician assisted suicide and tried various strategies to declare Oregon’s law unconstitutional. The most recent was the argument that physicians who prescribed medication that could enable a patient to end his life violated the Controlled Substances Act of 1970. These physicians, he believed, should have their federal prescribing privileges revoked and be prosecuted. Such measures would potentially have dire effects on physician prescribing sufficient pain medication for dying patients (see T. Quill and D. Meier, “The Big Chill: Inserting the DEA into End-of-Life care,” New England Journal of Medicine 2006;354: 1-3;). The Controlled Substances Act was intended to prevent the use of addictive medication as recreational drugs. Invoking it to prevent dying patients from exercising control over their deaths is sheer trickery, attempted sleight-of-hand to interfere with a medical practice of which the Administration disapproved. Fortunately, the trick failed and physicians can continue to prescribe opioids (which, parenthetically, are not typically the medications prescribed to aid in suicide) and other controlled substances to treat pain, shortness of breath, and additional symptoms near the end of life without fear they will be punished.

The bad news is that Chief Justice Roberts joined the predictable duo of Scalia and Thomas in dissenting from the majority opinion. We can anticipate that Judge Alito, when he is confirmed as the next member of the Supreme Court, which appears almost certain, will join with his ideologically motivated colleagues in interpreting the law so as to support his moral and political views. That still leaves a majority of justices, some of whom are considered liberal and others of whom are considered conservative, without these unfortunate biases. But it’s a tenuous majority, composed of Justice John Paul Stevens (age 85), Ruth Bader Ginsburg (age 72), Anthony Kennedy (age 69), David Souter (66) and Stephen Breyer (67). On the other hand, we have Justice Antonin Scalia (69), Clarence Thomas (57), John Roberts (50), and probably soon will have Samuel Alito (55). My geriatric word of the day is the fervent hope that Justice Stevens remains healthy for at least the next 2 years.