08 December 2017
Statins and Cognitive Impairment
Full list of notes for the article:
Our central nervous system is about 1/4 cholesterol
"It's Not Dementia, It's Your Heart Medication: Cholesterol Drugs and Memory - Scientific American -Why cholesterol drugs might affect memory
Statins and cognition: what can we learn from existing randomized trials?
Statin-associated adverse cognitive effects: survey results from 171 patients.
In 2005, Health Canada released a statement in the Canadian Adverse Reaction Newsletter suggesting a possible association between statins and memory loss. The onset of these adverse events described in the case reports varied, but most occurred within 1 year of statin initiation. Most of the cases (11/19) reported an improvement in cognitive symptoms once the statin was stopped or the dose reduced. In 2012, the Food and Drug Administration (FDA) issued a safety announcement to health care professionals, warning them about the potential risk of cognitive impairment (memory loss, forgetfulness, amnesia, memory impairment, confusion) with the use of statins for a period of 1 day to years. (see next link)
Memory loss and confusion have been reported with statin use. These reported events were generally not serious and went away once the drug was no longer being taken.
Statin side effects can be uncomfortable, making it seem like the risks outweigh the benefits of these powerful cholesterol-lowering medications.
Doctors often prescribe statins for people with high cholesterol to lower their total cholesterol and reduce their risk of a heart attack or stroke. While statins are highly effective, they have been linked to muscle pain, digestive problems and mental fuzziness in some people and may rarely cause liver damage.
Simvastatin is commonly prescribed for hypercholesterolemia to reduce vascular risk in patients. Some of these patients have dementia with cognitive defects of several domains. Although protective effects seem to be present, there is emerging evidence that statins cause cognitive impairment.
Statin-Related Cognitive Impairment in the Real World - You’ll Live Longer, but You Might Not Like It:
They say that the most dangerous kind of ignorance is not knowing what you don’t know. It took me a long time to realize I had statin-related cognitive impairment because I had no idea what it was.
Adverse effects of statins reported in older people include muscle-related symptoms, diabetes, impaired physical function and cognitive impairment.
Books on the topic:
"When Dr. Duane Graveline, former astronaut, aerospace medical research scientist, flight surgeon, and family doctor is given Lipitor to lower his cholesterol, he temporarily loses his short-term memory. Urged a year later to resume the drug at half dose, he lost both short-term and retrograde memory and was finally diagnosed in a hospital ER as having transient global amnesia (TGA). This is the "scary, appealingly written" account of his search for answers that his medical community didn't have -- the how and why of his traumatic experience, and what needs to be done to prevent the devastating side effects to body and mind from the escalating use of the statin drugs."
Simvastatin side effects
Zocor is simvastatin
If LDL levels are a precursor to heart disease, then why do only 50% of victims of heart attacks have elevated LDL? Maybe because the tests performed are not a good indicator of heart disease.
"In a large cohort of patients hospitalized with CAD, almost half have admission LDL levels <100 mg/dL."
Statins deplete CoQ10, so get it from food
HMA Co-A reductase inhibitors or statins inhibit one of the key steps in coenzyme Q10 synthesis. These drugs have been associated with a reduction in serum and muscle tissue coenzyme Q10 levels and may play a role in statin-induced myopathy(disease of muscle tissue). Given the low risk of toxicity and the potential benefit in treating statin-induced myopathy, a trial of 200 mg of coenzyme Q10 daily should be considered for these patients. The elderly appear to be more susceptible to coenzyme Q10 deficiency.
The real problem in heart disease is oxidized cholesterol. Normal un-oxidized cholesterol is harmless...
The “French Paradox” refers to the fact that although the French have notoriously high levels of cholesterol, high blood pressure and most of them smoke, they have low rates of heart disease
Hydrophilic or Lipophilic Statins?
Despite several reports of statin-associated cognitive impairment, this adverse effect remains a rare occurrence ahttps://www.ncbi.nlm.nih.gov/pubmed/22474137mong the totality of the literature. If statin-associated cognitive impairment is suspected, a trial discontinuation can reveal a temporal relationship. Switching from lipophilic to hydrophilic statins may resolve cognitive impairment.
If it is suspected that the statin is contributing to the symptoms(cognitive impairment), a drug-free period of 1 to 2 months is recommended prior to a rechallenge. Expert opinion suggests a switch to a less lipophilic statin, such as rosuvastatin or pravastatin, to limit drug entry into the central nervous system and diminish the effects on cognition.
Lovastatin, pravastatin, and simvastatin are derived from fungi, whereas atorvastatin, fluvastatin, and rosuvastatin are synthetic. Atorvastatin, lovastatin, and simvastatin are lipophilic, whereas pravastatin, rosuvastatin, and fluvastatin are more hydrophilic.
Lipophilic statins cross the blood-brain barrier more readily, which may lead to central nervous system complaints such as insomnia, although this is rare. Hydrophilic statins exhibit greater hepatoselectivity and less influence on smooth muscle proliferation.
Results: Significantly higher proportional reporting ratios (PRRs) were observed for lipophilic statins, which more readily cross the blood-brain barrier, (range: 1.47-3.51) compared to hydrophilic statins (range: 0.69-1.64).
Conclusions: Inconsistent with the FDA class warning, highly lipophilic statins with specific pharmacokinetic properties (atorvastatin, simvastatin) appear to confer a significantly greater risk of adverse cognitive effects compared to other lipophilic statins and those with hydrophilic solubility properties.
In a study comparing the two types of statins, cognitive impairment associated with statins use in 24,595 patients was significantly different in the two types of statins.
In conclusion, although, short-term cardiovascular outcomes were better in the lipophilic-statin group, long-term outcomes were similar in the hydrophilic- and lipophilic-statin groups in patients with AMI. In other words, statin type did not influence long-term outcomes in patients with AMI.
Hydrophilic statins, such as pravastatin and rosuvastatin, have less tissue absorption, except for the liver, and fewer side effects due to lower dependence on the cytochrome p450 enzyme
In a sub-analysis of the Multicenter Study for Aggressive Lipid-lowering Strategy by HMG-CoA Reductase Inhibitors in Patients with Acute Myocardial Infarction (MUSASHI-AMI) database, hydrophilic statins were shown to be superior to lipophilic statins for preventing new Q-waves and reducing cardiovascular events in normocholesterolemic patients with AMI
Furthermore, inflammation was attenuated (weakened in force or effect) by hydrophilic compared with lipophilic statins. [Inflammation is the cause of most health conditions. The hydrophilic statin causes less inflammation. -jw]
LDL Cholesterol - Small Particle LDL (sdLDL) vs Total LDL Levels:
LDL = LDL-C = What is tested for these days "Bad Cholesterol"
HDL = High density lipoproteins "Good Cholesterol"
HDL2b = most beneficial HDL molecule
LDL-P = LDL particle concentration = there are different particles sizes in LDL
sdLDL = sdLDL-C = Small Density Lipoproteins = new research shows this is a better marker for heart disease
LP(a) = consists of low-density lipoprotein (LDL) and apolipoprotein (a) [apo(a)]
apo A-1 = Apolipoprotein A-1 , low levels of this equates to low levels of HDL
apo B = Apolipoprotein B-100 = high levels of this are bad
lbLDL = large buoyant LDL = new research shows these may be protective of CHD
CAD = Coronary artery disease
CVD = Cardiovascular disease = involves heart or blood vessels
CVD includes CHD = Cardiovascular Heart Disease
CAD, CVD, CHD are essentially the same thing with small differences
Smaller apo(a) isoforms appear to be superior to sdLDL for the assessment of CAD risk. Their combined effect is synergistic.
An elevated Lp(a) cholesterol level in the bloodstream increases the “stickiness” of blood, and contributes dramatically to the formation of clots and the chance of a heart attack or stroke.
Lipoprotein(a) in Cardiovascular Diseases
Lp(a) levels have been associated with cardiovascular disease in numerous studies [72,104,105].
Some studies have suggested that the size of LDL-particles may be of importance. People whose LDL particles are predominantly small and dense, have a threefold greater risk of coronary heart disease. Furthermore, the large and fluffy type of LDL may actually be protective.
If you really want to find out the risk your cholesterol levels pose, you shouldn’t rely on a traditional lipid panel to do the job.Such cholesterol tests measure total LDL, HDL, and triglycerides, and they’re what most doctors will order—but they’re outdated!
Granted, standard blood lipid tests are useful for determining whether yourratio of total HDL to LDL cholesterolis within a healthy range. But those cholesterol tests won’t tell you about yourHDL and LDL fractions(that is, whether you have predominantly small dense cholesterol particles, or large buoyant ones).
Particle size is extraordinarily important, because research shows that small dense LDL cholesterol is inflammatory and toxic to blood vessels.
The three specific cholesterol tests:
NMR LipoProfile Test (developed by LabCorp)
Lipoprotein Particle Profile (LPP) Test (developed by SpectraCell)
Cardio IQ Report (offered through Quest Diagnostics
Traditional lipid testing measures the amount of LDL cholesterol (LDL-C) present in the blood, but it does not evaluate the number of particles of LDL (LDL-P). Some studies have shown that increased numbers of small, dense LDL particles (sdLDL) are associated with inflammation and are more likely to cause atherosclerosis than fewer light, fluffy LDL particles. Researchers think that the presence of an increased number of sdLDL could be one of the reasons that some people have heart attacks even though their total cholesterol and LDL cholesterol concentrations are not particularly high.
Small Dense LDL Cholesterol Concentrations Predict Risk for Coronary Heart Disease: the Atherosclerosis Risk in Communities (ARIC) Study:
Since sdLDL particles are smaller and contain less cholesterol, increased levels of sdLDL also represent an increased number of atherogenic(artery-clogging) particles, which may not be reflected by the levels of LDL-C (what normal cholesterol tests show- overall LDL)
An elevated concentration of LDL cholesterol is a major risk factor for CAD [4-6]. However, LDL consists of a heterogeneous spectrum of particles with highly variable atherogenic potential . Small dense LDL particles (sdLDL) are believed to be particularly atherogenic due to increased susceptibility to oxidation...
Conclusion:A significant difference in the proportion of sdLDL was observed between patients with CAD and otherwise highly similar patients without CAD
In summary, our results showed that sdLDL-C was highly
correlated with an atherogenic lipid profile and, in contrast to
lbLDL-C, predicted future CHD events in ARIC participants.
[translation: the new small particle LDL tests are much better at predicting heart disease than the old generic LDL-C tests -jw]
All of this means that your basic total cholesterol reading really doesn‘t mean much unless it's exceptionally high. What truly informs you and your doctor of your risk is the types of cholesterol fraction patterns you have—large or small LDL, and high functioning or low functioning HDL.
But because standard blood lipid tests won't reveal this information, you need to ask your doctor to order one of the newer generation cholesterol tests, such as theLipoprotein Particle Profile (LPP)test (developed by Spectracell), theNMR LipoProfile Test(developed by LabCorp), or theCardio IQ Report(offered through Quest Diagnostics).
The new benchmark ratio is triglycerides to HDL cholesterol. A study published in the journal Circulation found that people who had the highest triglyceride-to-HDL cholesterol ratios were 16 times more likely to develop heart disease than those with the lowest ratios.
The ideal triglyceride-to-HDL ratio, in my opinion, is 2:1 or less. So if your triglycerides are 100 mg/dL, for example, you want your HDL cholesterol to be at least 50 mg/dL.
"I especially like statins in men ages between 50 and 75 why not above 75 I'll tell you in patients over 75 I don't get as much bang for my buck in other words I don't really see the usefulness of a statin in elderly people because a more afraid of CNS(central nervous system) effects and memory effects." 2:00 mark
Should You Take Statin Drugs for Cholesterol?
What is Cholesterol Fractionation?
Despite its well-deserved notoriety as a cause of heart disease, cholesterol is essential for human health. It is the building block of steroid hormones, including the stress hormone cortisol and the male and female sex hormones, including testosterone and the estrogens. Cholesterol is also an essential component of the membranes that surround all human cells. More than simply holding cells together, these membranes have a crucial role in regulating cell function and allowing chemicals to pass into and out of cells.
Because cholesterol is so vital, the body does not rely on diet to provide it. In fact, most of the cholesterol in the blood is manufactured in the liver. Strict vegetarians who don't get any dietary cholesterol have admirably low blood cholesterol levels that reduce their risk of heart disease while providing plenty of cholesterol to keep their cells happy and their hormones flowing. Statin drugs reduce the liver's cholesterol production by targeting the enzyme HMG-CoA reductase; and by lowering blood cholesterol levels, they protect arteries from damage.
The brain has a higher cholesterol content than any other organ. In fact, about 25% of the body's cholesterol is found in this small organ, which accounts for less than 2% of the body's weight.
The brain is highly dependent on cholesterol, but its cholesterol metabolism is unique. Because the blood-brain barrier prevents brain cells from taking up cholesterol from the blood, the brain must produce its own cholesterol. Like the liver, brain cells depend on HMG-CoA reductase to produce cholesterol.
Because of the blood-brain barrier, changes in blood cholesterol levels are not necessarily reflected in the brain itself. In addition, the barrier keeps many chemicals, including medications as well as toxins, away from the brain. Among the cholesterol-lowering statin drugs, some are largely excluded because they are water-soluble, while others that are fat-soluble can enter, at least to some degree (see table).
Statin drugs and the brain
Water-soluble; Excluded : Pravastatin, Fluvastatin, Rosuvastatin.
Fat-soluble; May enter the blood-brain barrier: Simvastatin, Lovastatin, Atorvastatin
A 1998 review of studies that examined the relationship between cholesterol levels and violence concluded that the data "consistently showed increased violent death and violent behavior in persons with low cholesterol levels."
The relationship between cholesterol and depression or suicide is also complex. For example, studies from France and Canada linked low cholesterol levels to an increased incidence of suicide, and research from the Netherlands and Turkey reported an association between low cholesterol levels and depression. On the other hand, data from Hawaii found the reverse: High cholesterol levels were connected with an increased risk of suicide.
[This is because they are only measuring total LDL levels, which doesn't tell us much. Remember 50% of people who have heart attacks have normal LDL levels. What does that tell you?
Our overall LDL count is like a car. It is made of many parts. On the outside you can only see the cars make and model, which is equivalent to our overall LDL counts, what doctors call LDL-C.
Measuring our LDL-C is like trying to diagnose a transmission problem by looking at the color of the car. It won't tell us much. Only by looking at the inter-workings of the car, or the sdLDL, LP(a), and other compounds inside the LDL of a human, can we figure out what is wrong with the car, or the person. -joe]
More Studies on overall health:
A new study finds the chemical war against cholesterol using statin drugs was justified through statistical deception and the cover up of over 300 adverse health effects documented in the biomedical literature.
• Muscle damage (myotoxicity): view80 studies here.
• Nerve damage (neurotoxicity): view54 studies here.
• Liver damage (hepatoxocity): view32 studies here.
• Endocrine disruption: view16 studies here.
• Cancer-promoting: view9 studies here.
• Diabetes-promoting: view8 studies here.
• Cardiovascular-damaging: view15 studies here.
• Birth defect causing (teratogenic): view11 studies here.
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