What Were The Basic Results
Just over half of the 16,699 statin users and their 16,699 non-statin-using comparison group were female. The average follow-up time was five years.
Comparing sociodemographic and health characteristics, there were few significant differences between the statin users and non-users. An exception to this was age and history of chronic diseases such as high blood pressure.
Overall, the incidence of dementia was lower among the statin users than non-users, which calculated to statin use being associated with a 22% reduced risk of dementia .
The risk reduction with statin use was greater for women than men .
When looking at the type of statin, risk reduction was greatest with high-dose statins, and with use for more than three years.
However, on sub-analyses by type of dementia, the only significant association was found between statin use and any type of dementia with the exclusion of vascular dementia. There was no significant association between statin use and Alzheimers disease specifically, or statin use and vascular dementia specifically.
The Diagnostic Process May Differ
There can be more involved in arriving at a diagnosis of Alzheimers versus other forms of dementia. Aside from reviewing your medical history and ruling out other conditions, you might be evaluated by a neuropsychologist trained in brain conditions, notes the Mayo Clinic.
However, you might undergo brain-imaging tests that may indicate a progressive loss of brain cells that are associated with Alzheimers disease. However, its difficult to distinguish normal brain cell decline with Alzheimers using scans, so its not normally used in the diagnosis. Researchers are working on other methods to distinguish Alzheimers, such as using a scan that can detect an abnormal protein called tau.
Cholesterol Levels As An Ad Risk Factor
High levels of cholesterol, and particularly low-density liopoprotein cholesterol, are a well-established risk factor for developing coronary artery disease and stroke. There is an emerging impression that these may also be an AD risk factor, based on human epidemiological studies, human neuropathology studies, and experiments using animal models of AD, each of which we will review in order in this first part.
Although these diverse studies suggest a consensus that high cholesterol levels confer an increased risk of developing AD, some reported results do not fit with this conclusion. Reitz et al., for example, found that high total cholesterol levels in people 77 years and older the risk of AD . The individual effects of HDL and LDL cholesterol, however, were not significant. This group did not find any significant effect of total cholesterol, HDL, LDL, or triglycerides on cognitive ability in healthy elderly persons. A later study by Reitz and coworkers found that high total cholesterol or LDL levels were associated with a decreased risk of developing MCI in people 65 years and older . Mielke et al. similarly found that high total cholesterol levels between the ages of 7079 reduced the risk of developing dementia between the ages of 7988.
Relationship between outcome and age of participants in studies of cholesterols effect on dementia risk and progression
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Understanding Cholesterol In The Brain
Researchers are also interested in cholesterol in the brain, as this substance and the way that it is processed are very important for the health of brain cells, and may be affected in dementia. For example, one of the common genes that increase the risk of late-onset Alzheimer’s disease APOE4 plays a role in the processing and use of cholesterol and other fats. Understanding any differences may lead to clues about changes in the brain that cause dementia, and things that we could tackle with treatments.
Changes with cholesterol processing in the brain may not be related to the levels of cholesterol in the blood. More research is needed to better understand this relationship and what it can tell us.
Alzheimers Is Only Properly Diagnosed After Death
Further to the last point about doctors being able to see the effects of Alzheimers on the brain tissue, this can only be confirmed after the patient has died, notes LiveScience.com. Alzheimers can be diagnosed with complete accuracy only after death, when the brain is thoroughly examined during an autopsy, explains the source.
It notes a microscopic analysis of the brain tissue will reveal the plaques and tangles, which are the proteins we mentioned that are connected to Alzheimers disease. Until the patient passes away, doctors cannot rule out other causes, but can provide a diagnosis of dementia based on certain criteria.
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Characteristics Of Included Studies
A total of 2,513 articles were identified in our initial search. Of these, 2,475 articles were excluded, and 38 potentially relevant studies were subjected to full-text screening. Only 30 observational studies fulfilled all our criteria and were therefore included in our meta-analysis . Figure 1 shows the summary of excluded and included studies.
Fig. 1.
PRISMA flow diagram for study selection.
Table 1 summarizes the 30 eligible studies. These studies involved a total of 9,162,509 participants with 84,101 dementia patients from 23 cohort studies and 7 case-control studies . Of these, 20 studies were published in North America , 4 studies in Europe , and 6 studies in Asia . The eligible studies confirmed dementia patients by using standard protocols such as International Classification of Diseases, Ninth/Tenth revision-CM, DSM-IV, DSM-III-R National Institute of Neurological and Communicative Disorders and Stroke and the AD and Related Disorders Association, ADAS-Cog, 3MSE, whereas statin users were identified by the Anatomical Therapeutic Chemical Classification System. Of the 30 included studies, 3 studies had high methodological quality , 25 studies had moderate quality , and 2 studies had low methodological quality .
Table 1.
Baseline characteristics of included studies
What To Do If You Think Statins Are Causing Memory Loss
If you currently take a statin and are experiencing side effects like memory loss, mental confusion, or muscle pain, make an appointment to talk to your doctor today.
Go in armed with as much information on cholesterol as possible.
If youd like a deep scientific understanding of cholesterols role in the body, I recommend Dr. Peter Attias 9-part blog series The Straight Dope on Cholesterol.
Youll almost certainly know more about cholesterol than your doctor when youre done.
Tell your doctor that you want to have the small particle LDL test done.
As a matter of course, most doctors dont run this test.
Even doctors who understand the value of this test dont recommend it because its normally not covered by insurance.
You can ask for it anyway and offer to pay out of pocket.
Another test to consider is the Vertical Auto Profile or VAP test.
The Wall Street Journal has called the VAP test one worth paying for out of pocket.
And finally, remember that preventing heart disease, not simply having good numbers, is the real goal.
You can proactively prevent heart disease by adopting a heart-healthy lifestyle.
Drs. Bowden and Sinatra offer these simple lifestyle recommendations to address the true underlying causes of heart disease:
- Eat a diet of unprocessed foods
- Reduce sugar, grains, and vegetable oils high in omega-6 fats like canola oil
- Eat heart-healthy fats like nuts, olive oil, coconut oil, and avocado
- Manage stress
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The Alzheimers Disease Integrated Clinical Studies Dataset
Data were drawn from an integrated dataset of Alzheimers clinical trials and observational studies described previously . In brief, the datasets consisted of 18 studies from the Alzheimers Disease Cooperative Study and the Alzheimers Disease Neuroimaging Initiative conducted from 1993 to 2012 to analyze the decline on the Alzheimers Disease Assessment Scalecognitive subscale , the Clinical Dementia RatingSum of Boxes scale and the Mini-Mental State Examination over time. The integrated dataset includes demographics information, cognitive assessments, ApoE genotyping, concomitant medications information and blood test data for a total of 4574 participants, and 25,164 encounters. All diagnoses of AD were based on National Institute of Neurological and Communicative Disorders and Stroke/Alzheimers Disease and Related Disorders Association criteria . Statin use was captured from the concomitant medication logs using the following search terms: simvastatin, fluvastatin, atorvastatin, rosuvastatin, lovastatin, pravastatin, pitavastatin, Crestor, Lipitor, Lescol, Mevacor, Pravachol, Zocor and Livalo.
Re-analysis of a simvastatin trial
Fig. 1
Analyses workflows. a Re-analysis of simvastatin trial. b Analysis of continual use of statins from multiple AD trials and studies. c Analysis of statin use from the ROS/MAP studies. AD Alzheimers disease, MAP Memory Aging Project, ROS Religious Order Study
How Could Statins Do Both
Considering the evidence presented above, it is conceivable that statins can contribute to both reversible cognitive impairment as well as preservation of cognition through the prevention of dementia. If statins have both of these effects, there are a variety of possible explanations as to how this is occurring. The various physiological effects statins have on the body can explain how they can cause a myriad of different outcomes.
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The Link Between Statins And Memory Loss
While statin users have reported memory loss to the FDA, studies havent found evidence to support these claims. Research has actually suggested the opposite that statins may help prevent Alzheimers disease and other forms of dementia.
In a 2013 review, researchers from Johns Hopkins Medicine looked at 41 different studies on statins to see if there was a link between taking the medication and memory loss. Combined, the studies followed 23,000 men and women with no history of memory problems for up to 25 years.
The researchers found no evidence that using statins caused memory loss or dementia. In fact, there was some evidence that long-term statin use may protect against dementia.
Scientists believe this is because certain types of dementia are caused by small blockages in blood vessels that carry blood to the brain. Statins may help to reduce these blockages.
There remains some uncertainty about whether statins affect memory.
A 2015 study found that a small group of patients taking statins experienced amnesia. However, that finding may have been insignificant. The percentage of people taking statins who reported memory issues wasnt much different from those taking other cholesterol-lowering medications.
Like most medications, statins do have side effects. Other reported risks and side effects include:
- muscle pain and weakness
Sorting Through The Mixed Results
Ultimately, when it comes to the research on statins and dementia, there is enough inconsistency in the findings to conclude that if statins do have an effect on cognition, its probably quite subtle, says Dr. Manson.
If you take a statin and do experience symptoms, such as brain fog, confusion, or difficulty concentrating, it might be helpful to talk with your doctor about whether you should lower the dose or switch to a different type of statin, she says.
While the JACC analysis found no cognitive differences between people taking different types of statins, other research has found a higher rate of brain-related side effects related to a category of statins called lipophilic statins, says Dr. Manson. These include
- simvastatin
- lovastatin
- and atorvastatin .
Switching to a different type of statin, called a hydrophilic statin either rosuvastatin or pravastatin might be an option to discuss with your doctor, says Dr. Manson. Your doctor might also want to prescribe a non-statin cholesterol medication instead. Some examples are ezetimibe , alirocumab , and bempedoic acid .
Its important to keep in mind that even if you do experience side effects with one type of statin, dont stop taking it without having a conversation with your doctor.
“People shouldnt just stop taking a statin, because high cholesterol is a clear risk factor for heart disease and stroke, in addition to being a risk factor for cognitive decline,” says Dr. Manson.
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What Kind Of Research Was This
This was a population-based cohort study.
The study included over 33,000 people aged over 60 years from Taiwan and looked back at whether dementia developed in people who were and were not prescribed statins.
The researchers say that there has been some controversy in past research over whether there is any link between statin use and risk of dementia, and Alzheimers disease in particular.
The main limitation of this study, as with all cohort studies, is that it can demonstrate an association, but it cannot definitely prove cause and effect.
The study has adjusted for a number of potentially contributing factors that could be influencing the association including:
- age
- sociodemographic variables
- various long-term medical conditions coded in medical records
Still, this may not fully account for these or other health or lifestyle factors that may be involved in the relationship especially for such a complex condition as dementia.
Healthy Heart Healthy Brain
On the surface, it seems intuitive that statins would reduce the risk of cognitive problems, because many treatments that help your heart can also help your brain, says Dr. Manson. Conversely, high cholesterol levels, high blood pressure, and diabetes are all risk factors for heart disease, as well as for a condition called vascular dementia, in which impaired blood flow to the brain leads to cognitive changes.
“Statins also decrease inflammation, which has been implicated in Alzheimers disease and some other forms of dementia,” says Dr. Manson.
Although it seems to make sense that statins would bring brain benefits, the research doesnt always bear that out.
“While you would expect that statin use would reduce the risk of cognitive decline and dementia because statins lower cardiovascular risks and the risk of stroke, it hasnt been clearly shown to be the case,” says Dr. Manson. “Its surprising that theres not a clearer reduction seen. If anything, some of these studies have raised concerns about cognitive risks.”
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Memory Loss Is A Documented Side Effect Of Statin Drugs
Interestingly, the manufacturers of statin drugs are fully aware of their ability to interfere with memory and learning and to cause brain fog. In fact, these side effects are listed on the insert of every statin prescription bottle.
The reasons for this link are explained by Be Brain Fit:
Statins decrease the production of CoQ10, a nutrient thats protective of both the heart and the brain.
CoQ10 deficiency is believed to be responsible for the fatigue and muscle pain commonly experienced from statin drug use.
Some people get very irritable, depressed, anxious, or even suicidal when taking these drugs or when following a low-fat diet.
The U.S. Food and Drug Administration requires that warning labels state that statins can cause memory loss as well as mental confusion, liver problems, and type 2 diabetes.
Statins can lead to diabetes at an alarming rate.
Research has found that nearly half of women who take these medications eventually develop diabetes, a disease which greatly increases your risk for dementia.
High Cholesterol Is Beneficial
According to Dr. Ravnskov, high cholesterol is beneficial.
He states that the social campaign that cholesterol is harmful to your health is the greatest medical scandal in modern time.
Cholesterol is a waxy, whitish-yellow fat, and it is a crucial building block for all of your cell membranes. It is essential for making the membranes, and actually the entire cell structures, and is vital for synthesis of vitamin D, your hormones , and fat-dissolving bile acids.
Healthy brain function requires amyloid plaques that form in the brain. Researchers have found that higher levels of cholesterol are linked to having more amyloid in the brain. The higher levels of LDL cholesterol, the more amyloid in your brain.
Your body produces three to four times more cholesterol than you eat. The production of cholesterol increases when you eat little cholesterol, and decreases when you eat more. The brain has a higher cholesterol content than any other organ, but it doesnt use the cholesterol from your blood your brain produces its own cholesterol.
So heres my point: if your brain needs cholesterol to maintain healthy cognitive function, and statins keep the cholesterol levels lower in your brain, Dr. Ravnskovs research is right statins accelerate memory loss and Alzheimers.
In your body, cholesterol serves three main purposes:
- It aids in the production of sex hormones
- Its a building block for human tissues
- It assists in bile production in the liver.
It doesnt hurt to try.
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Statins And Memory Loss: Is There A Link
Statins and memory loss
Statins are one of the most commonly prescribed drugs for high cholesterol in the United States. However, recently there have been concerns over their side effects. Some statin users have reported that they experienced memory loss while taking the medication.
Statins Protect Against And Accelerate Cognitive Impairment And Dementia
At least 10% of the U.S. population is currently taking a statin to help lower cholesterol. But can statins help prevent dementia? More importantly, can these same statins accelerate dementia? And how can we explain how statins are responsible for such dramatically different responses? Let’s take a look.
Statin use is ubiquitous, and a careful read of the literature will demonstrate some small percentage of each clinical trial having increased or decreased risk of dementia and Alzheimer’s Disease . It is not a new issue in 2012, the FDA felt it necessary to warn physicians about a small but real incidence of reversible cognitive impairment associated with their use. Of course, the real-world evidence is a bit more ambiguous than that FDA pronouncement would suggest.
Cognitive impairment
Alzheimer’s Disease and dementia
- Two epidemiologic studies demonstrated a lower risk of dementia in statin users.
- Statin’s beneficial effects accrue to specific sub-groups, such as patients under age 80, and women. Similarly, the use of statins in mid-life seemed to reduce AD and dementia in later life.
- The effect of statins, if present, were not directly related to subsequent cholesterol levels.
- Several large clinical trials failed to demonstrate a benefit, but again, dementia was not a measured primary outcome.
- The Cochrane Systematic Review did not identify any protective effect.
Bioplausibility
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