Keeping your wits about your cholesterol

We have long known, and right we have been, that elevated blood cholesterol levels, notably LDL levels, are bad for hearts and arteries, and the bodies and minds those suffuse and serve. What then accounts for headlines like “High Cholesterol Linked to Better Brain Health in People Over 85” issuing from a study just published in Alzheimer’s & Dementia?

The answer, in a word, is: age. The slightly more elaborated five-word answer is: age as an effect modifier. An effect modifier is a factor that, as it changes, alters the relationship between two other factors. One example is the relationship among weight, illness and mortality.

We have talked ourselves into the mistaken belief that there is an “obesity paradox,” meaning a survival advantage to being overweight rather than lean. The reality, though, is that being lean portends better health outcomes than being either overweight or obese. But, people who are sick tend to lose weight, and being overweight, stable and basically well is better than losing weight due to illness. So, the presence of illness as a cause of weight loss alters, or modifies, the otherwise reliable relationship between body mass and mortality. Health status as the reason for weight loss is an effect modifier.

Another example dealing with widely familiar matters is the relationship among exercise, heart attack risk and coronary atherosclerosis. As we all know, exercise is good for health in general, and good for the heart specifically. Exercise throughout your life, and other things being equal, your chances of a heart attack will decline accordingly. But what if you suddenly take up intense exercise once you already have advanced coronary atherosclerosis? That is likely to cause a heart attack! Our recent, heavy snow poses just this kind of risk. The effect of exercise on heart attack risk just did a 180, because it was modified by the baseline status of the coronaries.

As for the study of dementia and cholesterol, the investigators set out to clarify the relationship among blood cholesterol levels, dementia and age. They followed nearly 2,000 participants in the Framingham Study who had normal cognition at the start. The researchers analyzed the associations between blood cholesterol levels at various times from midlife to advanced old age, and the change in cholesterol levels over time, with cognitive function. In general, elevated cholesterol levels throughout life were associated with a higher risk of cognitive impairment.

This association reversed, however, in the oldest group — those age 85 to 94. Those without cognitive impairment at 85 were actually less likely to develop it in subsequent years if their cholesterol was elevated, or even rising, than if it was normal or falling.

Like weight, cholesterol often falls as health fails. In particular, an occult cancer or other wasting illness in old age will tend to cause weight and cholesterol to begin falling together. We are led back to a fairly obvious truism: people over 85 healthy enough to maintain their cholesterol levels (and weight) are less likely to experience diminished cognitive function than those with some undiagnosed malady causing those levels to fall.

The obvious peril of effect modification is to generalize. The idea that high cholesterol is suddenly “good” for cognition is dangerous folly, on the basis of the current study, as well as many others. There is a small and unusual group that can reach advanced old age with high cholesterol and no apparent ill effects. The study highlights that interesting fact, and perhaps also implies that treating high cholesterol in those unharmed by it at age 85 would be ill advised. It does nothing to refute the harms of high cholesterol over time in everyone else.

Worth noting, too, is that by the standards of truly healthy populations, almost everyone in the U.S. has high cholesterol. In the world’s Blue Zones, people routinely live to advanced old age without dementia. They have a health-promoting culture and lifestyle, with resultant low cholesterol levels on average, to thank for it.

From the new research, we have learned it is possible to keep our wits and elevated cholesterol in tandem into the ninth and tenth decades of life. We now need to keep our wits about effect modification, the nuances of epidemiology, and what findings like these really mean.

Dr. David Katz