Do Statins Help Prevent Dementia

Effect Of Statins On Cognitive Decline And Dementia In Older Adults

Zhou Z, Ryan J, Ernst ME, et al., on behalf of the ASPREE Investigator Group.

Citation:

Mollie McDermott, MD, MS

Quick Takes

• In this large, prospective cohort study, statin use was not associated with incident dementia, mild cognitive impairment, or cognitive decline.
• No differences were found in any of the primary outcomes between users of hydrophilic versus lipophilic statins.
• These results are encouraging, but a randomized trial with dementia and cognitive decline as prespecified outcomes will be required to prove that statins do not worsen cognitive outcomes.

What The Research Tells Us

Observational studies have produced mixed results: a few early studies reported a significant preventative benefit but others since were much less encouraging. Large-scale randomized controlled trials are challenging for such a complex topic, but the authors of a recent systematic review found two, involving a total of 26,340 participants aged 40 to 82, almost half of them age 70 and over . They were given one of two different statins, monitored and assessed over a three to five year follow-up period, and compared with people in control groups who were given a placebo.

What did they find? Disappointingly, there was no evidence that statins have any effect in preventing cognitive decline or dementia .

If your doctor has prescribed statins, take them. And while youre at it, take any advice offered about lifestyle changes including diet and exercise. The pills alone may not be a magic solution for avoiding dementia but maintaining a strong, healthy heart and body will always have benefits.

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

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Do Statins Increase Or Decrease Alzheimers Risk

Is it possible for a medication both to increase and to decrease dementia risk? In the case of statins, this can appear to be true. Overall, the beneficial effects of statins seem to outweigh their small risk of interfering with cognitive functioning, but we cant ignore the many reports of memory impairment associated with these medications. How can this be? There is evidence both for statin-associated brain protection and for statin-associated cognitive interferenceand there is a credible explanation.

How Statin Drugs Protect The Heart

More than 200 million people around the world take statin drugs for theirheart health. Shifting ideas about the risks and benefits of statins overthe years, however, have left some new patients confused about whetherthese drugs are rightor safefor them.

Traditionally, statins were viewed as purely cholesterol-lowering drugs. So it made sense just to use them for people with high cholesterol, explains Johns Hopkins cardiologist Michael Blaha, M.D.But weve learned that they also benefit people with lower levels of cholesterol who are at a high risk of heart disease. So we now think of statins as risk-reducing drugs.

This dramatic change in thinking means that people who once were not candidates for statins are now prescribed them to lower their risk of heart attack and stroke.

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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.

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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Statins Doubled Risk Of Developing Dementia

Statins effects on cognitive performance have previously been called into question, since lower levels of low-density lipoprotein cholesterol are linked to a higher risk of dementia.8 The featured study, published in The Journal of Nuclear Medicine,9 involved people with mild cognitive impairment and looked into the effects of two types of statins: hydrophilic and lipophilic.

Hydrophilic statins, which include pravastatin and rosuvastatin , dissolve more readily in water, while lipophilic statins, such as atorvastatin , simvastatin , Fluvastatin , and lovastatin , dissolve more readily in fats.10 Lipophilic statins can easily enter cells11 and be distributed throughout your body, whereas hydrophilic statins focus on the liver.12

According to study author Prasanna Padmanabham of the University of California, Los Angeles, There have been many conflicting studies on the effects of statin drugs on cognition. While some claim that statins protect users against dementia, others assert that they accelerate the development of dementia. Our study aimed to clarify the relationship between statin use and subjects long-term cognitive trajectory.13

Further, this group also had significant decline in metabolism of the brains posterior cingulate cortex, which is the brain region that declines most significantly in early Alzheimers disease.15

Specific Combinations Of Drugs May Hold The Key To Reduced Risk

The study examined the medical and pharmacy claims of a random 20% sample of Medicare beneficiaries, aged 67 and higher, enrolled in traditional Medicare from 2007 to 2014. Researchers linked claims from Medicare Parts A , B and D to enrollment files that included beneficiaries characteristics such as race and sex.

To be included in the analysis, individuals had to have used both an antihypertensive and a statin for the two previous years and have no prior dementia diagnoses and no prior use of Alzheimers disease-specific medications.

Even small delays in onset can dramatically reduce the burden on patients, caregivers and the health system as a whole.

The study found the use of cholesterol-lowering drugs pravastatin and rosuvastatin, combined with ACE inhibitors or angiotensin II receptor blockers for high blood pressure, was associated with reduced risk for dementia as compared to other combinations of drugs.

The risk was especially lower for people using pravastatin and rosuvastatin in combination with ARBs, and more so for men than women.

The magnitudes of estimated risk reductions were meaningful for example, using ARBs combined with pravastatin was associated with 21% lower odds of a dementia diagnosis, as compared to individuals using other combinations of drugs.

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Other Readers Say Statins Make You Stupid:

Katy experienced brain fog on simvastatin:

Simvastatin wrecked my cognitive ability, causing memory loss, an inability to process or remember numbers. I also experienced brief episodes of lost time. It scared the hell out of me, given that my mother came down with early dementia. I am in my early 60s now.

I discontinued the medication about a month ago after getting my doctors okay. Its gotten a little better, but I am still experiencing some pretty severe side effects. It scares me. Im going to screw up big time on my job if I cant find a way to get my memory and full cognitive ability back soon.

Patty had concerns about her brain while taking a different statin:

I finally stopped rosuvastatin after many years of statin use. For the first time in a long time, I feel more clearheaded than I have for years. My fasting blood sugar has been steadily rising for the past several years, and then I read about the link to type 2 diabetes and statin use. That mobilized me.

Winnifred is afraid statins make you stupid, or more specifically, made her stupid:

Here is Pats story about statins and brain fog:

To learn more about statin side effects in general and cognitive problems in particular, you may wish to read our book, Top Screwups. It is available in the bookstore at PeoplesPharmacy.com.

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Statins Double Or Triple Diabetes Risk

A connection already exists between statins and diabetes, to the extent that people who take statins are more than twice as likely to be diagnosed with diabetes than those who do not, and those who take the drugs for longer than two years have more than triple the risk.23,24

The fact that increased duration of statin use was associated with an increased risk of diabetes something we call a dose-dependent relationship makes us think that this is likely a causal relationship, study author Victoria Zigmont, a graduate researcher in public health at The Ohio State University in Columbus, said in a news release.25

The data also indicated that individuals taking statin medications had a 6.5% increased risk of high blood sugar as measured by hemoglobin A1c value,26 which is an average level of blood sugar measuring the past 60 to 90 days.

Researchers with the Erasmus Medical Center in The Netherlands also analyzed data from more than 9,500 patients, finding those who had ever used statins had a 38% higher risk of Type 2 diabetes, with the risk being higher in those with impaired glucose homeostasis and those who were overweight or obese.27

The researchers concluded, Individuals using statins may be at higher risk for hyperglycemia, insulin resistance and eventually Type 2 diabetes. Rigorous preventive strategies such as glucose control and weight reduction in patients when initiating statin therapy might help minimize the risk of diabetes.

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Your Brain Needs Cholesterol

About 25% to 30% of your bodys total cholesterol is found in your brain, where it is an essential part of neurons. In your brain, cholesterol helps develop and maintain the plasticity and function of your neurons,16 and data from the Shanghai Aging Study revealed that high levels of LDL cholesterol are inversely associated with dementia in those aged 50 years and over.

High level of LDL-C may be considered as a potential protective factor against cognition decline, the researchers noted.17 They compiled a number of mechanisms on why lower cholesterol may be damaging for brain health, including the fact that lower cholesterol is linked with higher mortality in the elderly and may occur alongside malnutrition and chronic diseases, including cancer. As it specifically relates to brain health, however, they suggested:18

• High LDL cholesterol may be beneficial by reducing neurons impairments or helping repair injured neurons
• Acceleration of neurodegeneration has occurred when neurons were short on cellular cholesterol or cholesterol supply
• Cholesterol plays an important role in the synthesis, transportation and metabolism of steroid hormones and lipid-soluble vitamins, and both of these are important to synaptic integrity and neurotransmission

Lower cholesterol levels were also associated with worse cognitive function among South Korean study participants aged 65 and over, and were considered to be a state marker for AD .19

Cholesterol And Cognitive Function

The human brain contains 25% of the total cholesterol of the body. Cholesterol is a major lipid constituent of the myelin sheath and the membrane lipid rafts in neurons and astrocytes, participating in regulation of ion channel permeability, signal transduction, and other cellular functions . Lipoproteins have very limited permeability of the intact blood-brain barrier. Therefore, essentially all brain cholesterol is locally synthesized in astrocytes, which are the main source of cholesterol for neurons.

One of the pathological hallmarks of Alzheimer disease is the development of extracellular senile plaques, composed mainly of a small peptide known as amyloid- , thought to be a major causative agent in the development of AD. Cholesterol is believed to be an important factor in the regulation of A production, with high cholesterol levels being linked to increased A generation and deposition. Lower cholesterol levels shift amyloid precursor protein processing to nonraft regions of the membrane where the benign -secretase cleavage pathway is favored .

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Where To Learn About Other Drugs That Affect Brain Function

Many other drugs that affect brain function, but they are either not used as often as the ones above, or seem to affect a minority of older adults.

Notably, there has been a lot of concern in the media about statins, but a meta-analysis published in 2015 could not confirm an association between statin use and increased cognitive impairment. In fact, a 2016 study found that statin use was associated with a lower risk of developing Alzheimers disease.

This is not to say that statins arent overprescribed or riskier than we used to think. And its also quite possible that some people do have their thinking affected by statins. But if you are trying to eliminate medications that dampen brain function, I would recommend you focus on the ones I listed above first.

For a comprehensive list of medications identified as risky by the experts at the American Geriatrics Society, be sure to review the 2019 Beers Criteria.

You can also learn more about medications that increase fall risk in this article: 10 Types of Medications to Review if Youre Concerned About Falling.

Statins: How The Drug Prevents Heart Attacks And Strokes

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Statins are a vital medication for people suffering from high low-density lipoprotein , a dangerous type of cholesterol. They target production of the chemical in the liver, lowering levels which could over time cause atherosclerosis and cardiovascular disease . Some people experience memory loss as a potential side effect of Statins, and high cholesterol is associated with an increased risk of dementia.

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Statins Wont Protect Your Heart Health

Statins are effective at lowering cholesterol, but whether this is the panacea for helping you avoid heart disease and extend your lifespan is a topic of heated debate. Again in 2018, a scientific review presented substantial evidence that high LDL and total cholesterol are not an indication of heart disease risk, and that statin treatment is of doubtful benefit as a form of primary prevention for this reason.35

In short, these drugs have done nothing to derail the rising trend of heart disease, while putting users at increased risk of health conditions like diabetes, dementia and others, such as:

• Cancer36
• Triple risk of coronary artery and aortic artery calcification38
• Musculoskeletal disorders, including myalgia, muscle weakness, muscle cramps, rhabdomyolysis and autoimmune muscle disease39
• Depression40

In the event youre taking statins, be aware that they deplete your body of coenzyme Q10 and inhibit the synthesis of vitamin K2. The risks of CoQ10 depletion can be somewhat offset by taking a Coenzyme Q10 supplement or, if youre over 40, its reduced form ubiquinol. But ultimately, if youre looking to protect both your brain and heart health, avoiding statin drugs and instead optimizing your diet may be the answer.

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