Chapter 117
Taking the Pressure Off
In see.nf/cholesteroldementia I explain how cholesterol is not only involved in forming atherosclerotic plaques in our brain arteries, but also contributes to the amyloid deposits that run through the brain tissue of Alzheimer’s patients. Under the electron microscope, you can see the accumulation of amyloid fibrils on and around tiny cholesterol crystals. Pharmaceutical companies try to cash in on this connection and sell cholesterol-lowering statin drugs to prevent Alzheimer’s, but statins themselves can cause cognitive impairment, including short- and long-term memory loss. For people who are not willing to change their diet enough, the benefits of statins outweigh the risks, but it is better to lower your cholesterol level naturally with a healthy diet to protect your heart, brain, and mind.
In 2022, the most important recommendation of an expert consensus panel for preventing cognitive decline revolved around the concept “brain health equals heart health.” It is therefore no surprise that the centerpiece of the “Diet and Lifestyle Guidelines for the Prevention of Alzheimer’s” published in Neurobiology of Aging was: “Vegetables, legumes (beans, peas, and lentils), fruit, and whole grains as staple foods instead of meat and dairy products.”
Oxidized cholesterol from food
Total cholesterol levels in the brains of Alzheimer’s patients vary greatly at autopsy and are not necessarily higher than in people who died from other causes. But something else is the levels of oxidized cholesterol. These rise drastically in the brains of Alzheimer’s patients and also creep upward in the cerebrospinal fluid of people with mild cognitive impairment. This adds to the likelihood that oxidized cholesterol is “the driving force behind Alzheimer’s.” In the chapter “Oxidation,” you will learn how you can expose yourself to less of it.
Taking the pressure off
The first study with an effective strategy to prevent age-related cognitive impairment was published in 2019. An earlier study of 300 Alzheimer’s patients had found that treating vascular risk factors, such as high cholesterol and blood pressure, can slow the progression of the disease but cannot stop it. That is why prevention is crucial. For the SPRINT study (Systolic Blood Pressure Intervention Trial), more than 9000 older men and women with hypertension, with an average age of 68 years, were randomized to one of two treatment targets: medications that lowered the upper (systolic) blood pressure value to under 140, or even more medications that lowered systolic blood pressure to under 120, which is closer to normal blood pressure. The study was designed to run for six years, but the higher medication dose lowered overall mortality by 27 percent and saved so many lives that the study was stopped early, halfway through. But was mental health saved as well?
The SPRINT-MIND study examined the cognitive abilities of the SPRINT participants during the study and then for about two more years afterward. The 17 percent reduction in dementia in the intensive blood-pressure-lowering group was not statistically significant, but the 19 percent reduction in the risk of mild cognitive impairment was. Blood pressure reduction thus appears to prevent cognitive decline. The downside was the side effects of the number and dose of medications needed to normalize blood pressure. Yes, there was less heart failure in the high-dose group, but more kidney failure, fainting, and electrolyte abnormalities. A healthy diet and lifestyle would offer all the benefits: lower blood pressure and plenty of good side effects.
The brain arteries serve not only as conduits but also as cushioning. The elastic recoil of their walls acts like a shock absorber for the pulsating blood pumped up from the heart. However, if the artery walls stiffen with age, the pulse pressure can damage small blood vessels in the brain. That causes “microbleeds” in the brain, which occur about three times as often in people with high blood pressure, even if they have never been diagnosed with a stroke. High blood pressure is also associated with so-called lacunar infarcts, from the Latin lacuna, “hole.” On a CT scan it looks as if the brain has been perforated.
These holes form when small arteries in the brain are blocked, causing a pea-sized area of the brain to die. Up to a quarter of older people have these mini-strokes, and most don’t even know it. They are called “silent infarcts” because they do not have clinically obvious stroke symptoms, but they are still associated with small deficits in physical and cognitive functions and can double the risk of dementia. High blood pressure is also linked to brain shrinkage, especially of the memory center. No wonder elevated blood pressure in midlife carries an increased risk of cognitive impairment and later Alzheimer’s dementia—even more so than the presence of the so-called Alzheimer gene.
14 of 15 cross-sectional studies showed an association between increasing arterial stiffness and reduced cognitive performance, and six of seven longitudinal studies found that arterial stiffness is a harbinger of cognitive decline. How can we reduce the stiffening of arteries? Eat less salt! High sodium intake causes excessive arterial fibrosis, the accumulation of scar tissue in the artery walls, which makes them hard. A meta-analysis of eleven randomized controlled trials found that reducing salt intake by less than a teaspoon per day can significantly reduce arterial stiffness and also lowers blood pressure.
Arterial stiffness from excessive sodium intake is in fact one of the mechanisms by which too much salt raises blood pressure. By now, excessive salt consumption is also seen as a dementia risk factor independent of its effect on blood pressure, since it also impairs arterial function. In mice, heavily salted food directly leads to cognitive impairment and to the development of the brain pathology characteristic of Alzheimer’s.
Diet beats genetics
Few people seem to be aware of the good news that a large share of Alzheimer’s risk is modifiable. For example, in one study only about a quarter of respondents knew that high cholesterol and high blood pressure increase risk. A scoring system was developed that predicts the probability of a dementia diagnosis in the next 20 years, based on factors we can influence. According to the scoring system, a 50-year-old man without a high school diploma, physically inactive and overweight, with high blood pressure and high cholesterol, has a more than 50-fold higher dementia risk than an educated, active, non-obese 50-year-old man with normal blood pressure and cholesterol. So we have enormous influence over our risk.
Even so, the mass media say Alzheimer’s is genetic, not a consequence of our lifestyle that determines whether we develop it or not. However, as I show in detail in the chapter on brain diseases in How Not to Die, Alzheimer’s is distributed very unevenly worldwide, which is why that claim begins to crumble.
The lowest confirmed Alzheimer’s rate is found in rural India, where the traditional plant-based diet consists largely of grains and vegetables. More recently, a study from Taiwan found that vegetarians have only two thirds the dementia risk of nonvegetarians. In the United States, a study showed that those who do not eat meat (including no poultry or fish) cut their dementia risk in half. And the longer you abstain from meat, the more dementia risk declines. Compared with people who eat meat more than four times a week, others who had been vegetarian for at least 30 years had a threefold lower dementia risk.
In the gray box below you can see how much control we fortunately have over the “Alzheimer gene” ApoE4. Too often physicians and patients face chronic degenerative diseases with resignation, and Alzheimer’s is no exception. “It’s all in the genes,” they say, “and what has to happen will happen.” But research shows that even if, genetically speaking, you have been dealt a bad hand, you can reshuffle those cards through diet.