Transcript: Cholesterol and Alzheimer’s Disease
Millions suffer from Alzheimer’s disease. And, the available and foreseeable treatments are disappointing at best. Given the absence of disease-modifying treatments, there has been growing interest in effective strategies for the prevention of the disease in the first place. Even if we were able to just delay the onset by as little as one year, we could potentially prevent more than nine million cases over the next 40 years.
Once cognitive functions are lost in Alzheimer’s disease patients, they may be lost forever. Consequently, prevention, rather than a cure for Alzheimer’s Disease, appears as a more realistic strategy to offset the catastrophic impact of this dementia.
Considerable evidence now indicates that Alzheimer’s Disease is primarily a vascular disorder, based on a number of lines of evidence that point toward impaired circulation of blood to the brain.
Vascular risk factors, such as high cholesterol, can be thought of as a ticking time bomb to Alzheimer’s Disease. What’s bad for the heart may be bad for the mind.
Traditionally, there have been two competing theories for the cause of Alzheimer’s: the amyloid cascade model that implicates the buildup of amyloid plaques within the brain, and the vascular model, that argues that it is the lack of adequate blood flow to the brain due to atherosclerosis. We now realize they are not mutually exclusive, and that arterial disease can set up a vicious cycle, in which atherosclerotic plaques in the arteries may contribute to Alzheimer’s plaques in the brain.
Although at times portrayed as tantamount to poison, cholesterol is an essential structural component of all of our cells, but if there’s too much, it can become a major factor contributing to various diseases, including coronary heart disease, stroke, and neurodegenerative diseases, like Alzheimer’s. Too much cholesterol in our blood is unanimously recognized to be a risk factor for the development Alzheimer’s disease, and cholesterol may play an active role in the progression of Alzheimer’s as well.
Autopsy studies have found that Alzheimer’s brains have significantly more cholesterol than normal brains, and it specifically appears to accumulate in the Alzheimer brain plaques. We used to think the pool of cholesterol in the brain was separate from the pool we had in our blood, but there is now growing evidence to the contrary. For example, LDL may be able to cross the blood–brain barrier into the brain. So, a high-fat diet may not only increase cholesterol levels in the blood, but also the influx of cholesterol into the central nervous system.
In addition, having high cholesterol may even damage the blood brain barrier itself, and allow for even more cholesterol to flow into the brain, providing the missing link between high cholesterol and Alzheimer’s. Individuals with higher cholesterol levels at midlife have a higher risk of going on to develop Alzheimer’s disease. Cholesterol over 250 could potentially triple the odds of Alzheimer’s.
And now we have high-tech PET scanning of the brain that can directly correlate the amount of so-called bad cholesterol in our blood with the amount of amyloid build up in our brains. You can do it right in a petri dish. Adding cholesterol makes them churn out more the amyloid that makes up Alzheimer plaques, whereas removing cholesterol can decrease the levels of amyloid released from the cells.
In addition, amyloid degradation is less efficient in a high cholesterol environment. Cholesterol can then help seed the clumping of the amyloid. Using an electron microscope, you can see the clustering of amyloid fibers on and around little microcrystals of cholesterol.
Once in the brain, cholesterol can also undergo auto-oxidation, causing the formation of highly toxic free radicals. So, having high cholesterol levels in the blood is thought to increase the risk of dementia, not only by inducing atherosclerosis and impairing blood flow, but they may also directly affect neurodegeneration within the brain. In conclusion, excess dietary cholesterol could, in principle, contribute to the development of Alzheimer’s disease, and the evidence linking high cholesterol to Alzheimer’s appears to be steadily mounting.
Of course, some of this work was paid for by drug companies hoping to capitalize on Alzheimer’s with cholesterol-lowering statin drugs. Ironic, since statins themselves can cause cognitive impairment. Though rare, statin side-effects may include short- and long-term memory loss, behavioral changes, impaired concentration and attention, paranoia, and anxiety, as early as five days after starting the drugs, but sometimes even months later, though folks should recover within a month of stopping the drugs.
A better strategy may be to change the lifestyle factors that lead to the high cholesterol in the first place, in particular, reducing saturated fat in the diet, but it’s not enough for us to just tell our individual patients. Systematic implementation of educational campaigns promoting radical changes in cultural and societal values may be necessary to adopt Alzheimer’s defeating strategies by patients in a broader sense, and such actions "may provide potentially huge dividends by preventing both cardiovascular disease and dementia," two of our leading causes of death.
To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video. This is just an approximation of the audio contributed by Katie Schloer.
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