Lipophilic statins linked to higher risk of dementia

Atorvastatin and simvastatin are lipophilic statins and, unlike hydrophilic statins, have been linked to a higher risk of dementia; is this because of the statin, cholesterol levels, higher blood sugar or something else?

UCLA researchers have found that older adults with mild cognitive impairment are more than twice as likely to develop Dementia over the following 8 years if taking a Lipophilic statin, when compared to those not taking a statin, or taking a Hydrophilic statin.

The researchers of the Molecular and Medical pharmacology student research programme, separated older adults into groups based on three factors: the type of statin used, their initial cognitive status; and their initial cholesterol levels.

Of 303 participants with mild cognitive impairment, 200 had total cholesterol levels that were near-normal or normal. Researchers found that this was the most at risk group – indeed the only at risk group (1).

While in the non-statin takers, 10% went on to develop dementia, and only 11% of the hydrophilic statin users did, in the Lipophilc statin users group 24% developed dementia in the next 8 years.

Lipophilic statins: include the widely used Atorvastatin (Lipitor), Simvastatin (Zocor) and Lovastatin (Altoprev).

Hydrophilic statins: include Rosuvastatin (Crestor) and Pravastatin (Pravachol).

While both groups lower blood fat and particularly LDL, (bad) cholesterol, the main action of hydrophilic statins is in the liver. Lipophilic statins are fat soluble so can cross membranes reducing fat in the tissues as well. For this reason, lipophilic statins have found a new off-label market – in cancer treatment.

The benefits of crossing membranes may be good for fighting cancer which uses fat to spread,, but this ability allows lipophilic statins to cross the blood brain barrier as well with potentially dangerous side-effects.

Professor Dan Silverman of UCLA suggested that people didn’t ditch their statins, but he did suggest older people who had normal levels of cholesterol, might switch to a hydrophilic brand if they were concerned.

Why might Lipophilic statins increase the risk of dementia?

1. They cross the blood brain barrier and cholesterol is used – needed – by the brain. Cholesterol maintains good function.
2. The research on cholesterol levels and dementia is mixed but a study on 85 year olds showed less decline in memory and thinking if they had higher levels of cholesterol (2).
3. This is in contrast with an 18 study meta-analysis showing that people in mid-life with higher cholesterol were more at risk of dementia later in life (3). This study did not look at the effect of statins that this group were obviously more likely to take.
4. People with high cholesterol have lower vitamin D levels. No causal effects have been proven. However, low vitamin D is linked to a doubling of risk of Dementia (4).
5. People who take statins have a higher risk of Diabetes (5). There is a link between higher blood sugar, diabetes and levels of amyloid plaque – and this can lead to dementia.
6. There’s research that statins can lower Coenzyme Q10 levels and this is crucial in mitochondrial function, especially in high energy tissues like the muscles and the brain (see ‘Go to’ below).
7. Maybe the people with higher cholesterol in mid-life, pay less attention to their health and are more likely to have high blood pressure, low vitamin D, insulin resistance, higher blood sugar and metabolic syndrome (6). And this puts them at a greater risk of dementia.These people would be less likely to take exercise and we know that people who exercise develop less dementia.

Is the link between statins and dementia due to increased blood sugar?

Statins are known to increase plasma glucose levels in the body, and an early study showed that taking statins was associated with a 27% increase in the risk of type-2 diabetes.

In a 2013 study using data taken from the Ontario Drug Benefit database, the Canadian Institute for Health Information Discharge Abstract Database and the Ontario Diabetes Database, researchers found similar results – that patients treated with atorvastatin have a 22% increased risk of new-onset diabetes, rosuvastatin an 18% increased risk and simvastatin a 10% increased risk, relative to pravastatin (BMJ, 23 May 2013).

This followed a 2012 study (7) amongst post-menopausal women on statins) where women who are given cholesterol-lowering statin medication had a 44 percent increased risk for becoming a type-2 diabetic.

Statins are a class of medications called 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, and they block a critical step in the production of LDL (bad) cholesterol in the liver thus reducing blood levels of LDL.

There is some evidence that they reduce inflammation in the body, and promote the health of the lining of blood vessels.

Diabetes doubles Alzheimer’s risk

However, according to the Mayo Clinic, diabetes, in turn, doubles your risk for Alzheimer’s disease. This may be due to poor sugar control, links in inflammation, or the fact that diabetes is known to damage blood vessels and this might lead to problems of blood to the brain.

In 2005, a study by Brown University in Providence, Rhode Island, identified one reason why people with type-2 diabetes had a higher risk of developing Alzheimer’s.

They showed that your hippocampus, the part of the brain involved in learning and memory, seemed to be insensitive to insulin. So, the researchers basically suggested diabetes and Alzheimer’s were the same disease, where your muscle, liver and brain tissues all became insulin insensitive.

It is well known by scientists that giving animals a diet to replicate diabetes leaves their brains full of beta-amyloid plaque. Researchers have hypothesized that memory problems associated with diabetes are merely early stage Alzheimer’s.

The researchers also concluded that the amyloid build-up was not a consequence of cognitive decline but a cause, and that amyloid plaque might build up to protect the brain against high blood sugar and insulin activity.

What can I do?

There is evidence elsewhere on this Website that the following options may help:

1. Reduce Fasting Blood sugar levels, naturally or through a Ketogenic Diet.
2. Switch to a Hydrophilic statin.
3. Take 750 mg of Resveratrol before bed with 100 mg CoQ10.
4. Take up to 200 mg of CoQ10
5. Pay more attention to better sleep. Go to bed earlier, switch from blue light to night shift on mobile phones and computers, take melatonin, improve gut health.

Go to: Lipophilic statins extend life in cancer patients

Go to: Statins, CoQ10, cancer and dementia

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References

1. Prasanna Padmanabham, student research program, molecular and medical pharmacology, University of California, Los Angeles. nResearch presented online at the conference of the Society of Nuclear Medicine and Molecular Imaging annual meeting, June 11 to 15, 2021
2. Alzheimer’s Research UK – https://www.alzheimersresearchuk.org/better-memory-thinking-seen-85s-despite-high-cholesterol/
3. Meta-asnalysis of cholesterol in mid-life and Alzheimer’s; 2008; May; Kaarin J Anstey et al; Am J Geriatric Psych https://pubmed.ncbi.nlm.nih.gov/18448847/ .
4. Vitamin D keeps dementia at bay – https://chriswoollamshealthwatch.com/your-illness/alzheimers-and-dementia/sunshine-can-keep-dementia-at-bay/
5. Statins double risk of diabetes – https://chriswoollamshealthwatch.com/your-illness/diabetes/statins-can-double-risk-of-diabetes/
6. Metabolic syndrome – https://chriswoollamshealthwatch.com/your-illness/cardiovascular-disease/metabolic-syndrome/
7. Arch Intern Med. 2012 Jan 23;172(2); 2011.625E pub 2012 Jan – https://pubmed.ncbi.nlm.nih.gov/22231607/