"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 towards 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 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 our cells,
it's why our body makes it
but if there’s too much it can become a major factor
contributing to various diseases including coronary artery 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 specifically appears to accumulate in the Alzheimer brain plaques.
But 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.
A 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 brain.
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 level
of amyloid released from cells.
In addition, amyloid degradation is less efficient,
clearing amyloid 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 may directly affect
the 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 then, may be to change the lifestyle factors
that lead to the high cholesterol in the first place,
in particular saturated fat from 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.