Chapter 130
There Are No Randomized Controlled Trials on Parachutes
After reading this chapter, you may be surprised if, in summaries of what we can do against cognitive decline, you read something like: “The literature provides insufficient evidence to recommend specific measures.” Scientists justify such conclusions with the lack of randomized controlled trials. For testing new drugs, randomized controlled trials are indisputably the gold standard. This highest level of evidence is necessary because an estimated 100 000 Americans die each year from medications. I am not talking here about overdoses, medication errors, or illegal drugs. Completely normal, FDA-approved prescription drugs are the sixth leading cause of death in the United States. So you have to be absolutely sure that the benefits of new medications outweigh their life-threatening risks.
When it comes to a healthy lifestyle, however, the side effects are essentially all good, so we hardly need the same level of proof in order to prescribe it. In my video see.nf/rctdementia, I present the “modest proposal” for a series of randomized controlled trials on dementia prevention that was published in the Journal of Alzheimer’s Disease. To really know whether traumatic brain injuries increase dementia risk, wouldn’t we actually have to randomly hit people over the head with a baseball bat? And how can we doctors recommend to our patients that they not let themselves be hit on the head as long as we have no randomized controlled data? And while we’re at it, we could also chain a few thousand people to a treadmill or a couch for a few decades, or force them to smoke. My report ends with the words: “It is time to recognize that the ultimate study … with regard to lifestyle and cognitive health in old age cannot exist. Yet the lack of definitive proof should not prevent physicians from making reasonable recommendations based on the available evidence.”
A randomized controlled trial that aims to find out whether a whole-food plant-based diet and a changed lifestyle can slow, halt, or even reverse the course of Alzheimer’s is nearing its end as I write these lines in 2023. To that end, Dr. Dean Ornish and his colleagues randomly assigned 51 patients with early-stage Alzheimer’s to the same diet and lifestyle program with which Ornish had already reversed heart disease, type 2 diabetes, high blood pressure, high cholesterol, and early-stage prostate cancer. Because this book would be published before the first results were announced, Dean gave me an exciting preview of the preliminary finding—and what can you say: It looks like the plant-based lifestyle is more effective than the new 50 000 dollar biotech infusions, without the brain swelling and bleeding in the process.
Preserving Muscle
In every animal species studied to date, the loss of muscle mass is a hallmark of aging. In humans, muscle loss begins at 30 and accelerates from 50 to 1 to 2 percent per year. By age 80, about 50 percent of the muscle fibers in the limbs are gone. The annual loss of muscle strength can be even more dramatic, meaning that not only quantity but also quality suffers. This is not only because people become less active as they age. Even in elite athletes such as marathon runners and weightlifters who stay fit their entire lives, performance tends to decline starting at 40, and by 80 only half remains.
A Pound of Flesh
An excessive age-related loss of skeletal muscle mass, strength, and function is referred to as sarcopenia, from the Greek sarx for “flesh” and penia for “loss.” About 25 percent of us have sarcopenia by the late 60s. Among 80-year-olds it is 40 percent, and among those over 70 in nursing homes it is nearly 70 percent.
Sarcopenia is not only associated with an increased risk of falls, but also with a shorter life expectancy overall. Loss of muscle strength may be even more crucial, since it is associated with mortality independent of muscle mass. This applies to both upper- and lower-body strength, although grip strength is typically used as a proxy for total-body strength. Each kilogram of performance decline in grip strength per year is associated with a 33 percent higher risk of death. Even in middle age, grip strength says a lot about possible disability 25 years later.
A closely related concept is frailty. Although known for centuries, its definition was not standardized until 2001. It is present when at least three of the following five criteria are met: weakness (measured in grip strength), unintentional weight loss (five kilos or five percent of body weight in the past year), exhaustion (self-reported), slow walking speed (measured over a distance of about 4.5 meters), and low physical activity. If only one or two of these criteria are met, this is referred to as pre-frailty. At age 65, about 1 in 40 is frail; at 75, 1 in 4; and among those over 85, 1 in 3.
Muscle mass and strength can be 50 to 60 percent genetically determined. What can we do for the remaining percent—the part we may have some influence over?
Use it or lose it
A study that followed Americans over 65 with low physical activity for twelve years found that they lose about one percent of muscle mass each year. Quite different in a comparable study in Japan: there the age-related decrease in muscle mass was “insignificant.” Why this difference? In the Japanese study, participants were kept informed about their results, so they often tried to improve their strength through training before the next assessment. This was especially true for middle-aged men, who were so ambitious that their muscle mass even partially increased with age. This shows that steady muscle loss with aging is not inevitable. You just have to do something about it.
Although we have not yet found the best “dose”—timing, frequency, and repetitions—resistance training is considered the most effective strategy for preventing age-related muscle weakness, treating muscle loss, and improving physical function. For example, in a typical 24-week strength-training program with three training sessions per week, men and women averaging 70 years of age achieved an increase in leg muscle mass of about 10 percent, an increase in lower- and upper-body strength of 40 percent, and about a 20 percent reduction in sit-to-stand time, a measure of mobility that can predict fall risk. Exercise interventions are considered key to maintaining independence among frail and pre-frail people, but they can also reverse a frailty classification. Frail men and women averaging 80 years old were randomized to a program that combined endurance, strength, coordination, balance, and stretching exercises for one hour a day, five days a week. In the control group, all 49 people were frail at baseline and remained so. But in the exercise group, 16 of the 51 (31 percent) were able to reverse their status after six months.
On the other hand, inactivity—or a decline in activity—can actively make things worse. Everyone loses muscle mass when lying in bed for days, but in older people it appears to happen six times faster than in younger people. After just ten days of bed rest, older study participants (average age 67) lost one kilo of lean muscle mass in their legs—more than younger participants (average age 38) lost in an entire month. Immobilizing one leg with a knee brace caused a similar decline in muscle strength (about 10 percent) in young and old people over four days, but a week later strength in people in their mid-20s had fully recovered, whereas those over 60 had not yet recovered. This is one explanation for why 30 to 60 percent of older patients can partially lose their independence in activities of daily living during a single hospital stay.