Jul
20
2019

Common Drugs Have A Connection To Dementia Risk

By | Cancer, Dementia, Drugs, epilepsy, Parkinson’s disease, seizure disorder

A recent publication stated that common drugs have a connection to dementia risk. The study had an observation time of 12 years (from 2004 to 2016) and involved 284,343 patients in the United Kingdom. There is a group of drugs, namely anticholinergic drugs, that were particularly strong with regard to causing side effects of dementia. A variety of anticholinergic drugs exist, such as antidepressants like paroxetine or amitriptyline. But there are other anticholinergic drugs like bladder antispasmodics (they also go by the name bladder antimuscarinics, such as oxybutynin or tolterodine). Other anticholinergic medications are antipsychotics that are in use for psychotic diseases. Examples are chlorpromazine or olanzapine. Anti-epileptic drugs also belong into the anticholinergic drug group. Common anti-epileptic drugs are oxcarbazepine or carbamazepine.

The researchers found that 58,769 of the patients that took strong long-term anticholinergic medication developed a dementia diagnosis.

More about the study

The researchers found that the risk of developing dementia for those who consumed only a few anticholinergic drugs was low. It amounted to only 6%. In contrast, patients who took a lot of anticholinergic drugs at least for 3 years or more developed dementia in 49% of all cases, which is quite a significant amount.

Dr. Douglas Scharre, director of the division of cognitive neurology at the Ohio State University Wexner Medical Center in Columbus was not involved in the study. He said: ”I spend a lot of my time in the memory disorder clinic seeing geriatric patients and taking people off medications, mostly those medications that have anticholinergic properties. Many times there can be another drug out there that has less anticholinergic impact or is non-anticholinergic that may work.”

Risk-benefit discussion

He went on to say that some drugs are really necessary to control a psychosis or seizures, so it is a matter of discussing with the physician whether it is worth taking a risk of possible dementia versus a risk of a flare-up of psychosis or of a seizure.

More statistics

Patients who received treatment for depression with anticholinergic antidepressants had a risk of 29% of developing dementia. Anticholinergic anti-Parkinson drugs had an association of a rate of 52% of dementia. Anti-psychotic drugs led to dementia in 70% of the treated cases. Bladder relaxing medications (medically called antimuscarinic drugs) had a risk of 65% to cause dementia. Finally, anti-epileptic drugs had a risk of causing dementia in 39%.

The researchers noted that these findings highlight how important it is reducing exposure to anticholinergic drugs in middle-aged and older people.

Serious side effects from other medication

Unfortunately there is a history of serious side effects regarding several medications.

Tardive dyskinesia with antipsychotics

Long-term treatment of schizophrenia with antipsychotic drugs can cause severe side effects. One of the more severe side effects is tardive dyskinesia, which occurs in 5% per year of antipsychotic medication use, and in about 1%-2% of these it is severely disfiguring the face. Tardive dyskinesia can lead to permanent involuntary movements of the muscles around the mouth and the eyes. The jaw and the tongue may also show involuntary movements, and in time this leads to a disfigured look of the face, often with asymmetries between the right and left side of the face. Unfortunately, withdrawal of the antipsychotic medications will not improve the tardive dyskinesia. Often expensive lifelong Botox injection therapy every 6 to 8 weeks is necessary to alleviate some of the effects of this devastating dyskinesia.

Side effects from antacid pills

Lansoprazole (Prevacid) belongs to the proton pump inhibitors and is a very strong acid production inhibitor. Because it is so reliable in suppressing stomach acid, it is popular with the public. What is not so well known are the side effects of this drug. The most common side effects are about bone fractures, severe diarrhea, kidney damage, systemic lupus erythematosus and fundic gland polyps. These polyps can later turn into stomach cancer. Unfortunately, drug companies do not always report about the less frequent side effects.

A rare side effect: muscle tremor

One of these side effects is a muscle tremor (jerking movements or shaking). It is listed under the side effects way down the list where you may overlook this. To the patient it can be devastating as the symptoms are very similar to Parkinson’s disease. Imagine a 40-year old man taking this medicine for stomach acid and coming down with these muscle tremor symptoms! Fortunately, when you recognize the connection, you can stop the medication and the symptoms frequently go away or at least diminish.

Rhabdomyolysis from statins

When a patient is receiving statins because of high cholesterol, one of the possible side effects can be rhabdomyolysis. This typically presents with muscle weakness, fatigue, and lower urine output. The urine may be of a dark color. Confusion, vomiting and agitation can also set in. It is necessary to immediately recognize these type of side effects, and the statin drugs should be stopped. The patient requires a kidney specialist to watch the kidney function. Often these patients need treatment in hospital. 

Cancer and heart attacks from synthetic hormones

The “Women’s Health Initiative” with a study on 16,000 postmenopausal women had to be stopped prematurely in 2002. This was a study that examined the effects of two synthetic hormones, the estrogen Premarin and the progesterone-like substance Provera. The purpose of the study was to show whether heart attacks, osteoporosis and strokes would be reduced on hormone replacement compared to controls. But the results were shocking: the opposite was true! The risk in the treatment group for strokes was 41% higher than for the controls and for heart attacks it was 29% higher! But this was not all. The treatment group had twice as many blood clots in their legs and 26% more breast cancer. Colorectal cancer was 37% higher and Alzheimer was a whopping 76% higher than in the controls.

Synthetic hormones caused estrogen dominance

The synthetic hormones functioned like xenoestrogens, meaning that there was a partial resemblance of the synthetic hormones to estrogen and progesterone, blocking their hormone receptors, but not stimulating them. The end result was an estrogen dominance state in the blood, which caused all of the problems. When bioidentical hormone replacement is done with bioidentical estrogen and progesterone, the opposite is the case. Women live longer because they get less heart attacks and strokes; they also get less cancer. In Europe bioidentical hormone replacement has been in use for over 50 years, and in the US physicians who use bioidentical hormone replacement have experience for almost 30 years.

Discussion

We started this article describing side effects of anticholinergic drugs and how this can bring on dementia. Other researchers have noted that dementia and strokes can be brought on by diet drinks. We then got into side effects of other drugs like tardive dyskinesia with antipsychotic drugs. We discussed the possibility of tremors from antacid drugs. A rare side effect of statins is rhabdomyolysis. And we talked about cancer and heart attacks from synthetic hormones in postmenopausal women. We need to be aware that any chemical brought into our system can cause undesirable side effects. Chemicals like drugs can interfere with biochemical reactions in the body that ultimately result in side effects including cancer and heart attacks.

Common Drugs Have A Connection To Dementia Risk

Common Drugs Have A Connection To Dementia Risk

Conclusion

In a recent publication we learnt that patients who took a lot of anticholinergic drugs at least for 3 years or more developed dementia in 49% of all cases, which is quite a significant amount. But there are other drugs that have serious side effects. For instance, there is tardive dyskinesia, a disfiguring condition in the face that can develop with antipsychotic medicine for schizophrenia. Statins can cause a painful muscle condition, rhabdomyolysis. The “Women’s Health Initiative” showed a study that examined the effects of two synthetic hormones, the estrogen Premarin and the progesterone-like substance Provera.

Synthetic hormones causing problems

The purpose of the study was to show whether heart attacks, osteoporosis and strokes would be less on hormone replacement compared to controls. Unfortunately quite the opposite happened. The risk in the treatment group for strokes was 41% higher than for the controls and for heart attacks it was 29% higher! But this was not all. The treatment group had twice as many blood clots in their legs and 26% more breast cancer. Colorectal cancer was 37% higher and Alzheimer was a whopping 76% higher than in the controls. Only bioidentical hormones are tolerated without any side effects. We need to treat our bodies with respect and stay away from noxious substances.

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Sep
07
2018

Two Proteins Responsible For Getting Epilepsy

By | epilepsy, neurological disease, seizure disorder

Epilepsy is sometimes difficult to control, but research has now identified two proteins responsible for getting epilepsy. According to the researchers this finding has the potential of turning our current knowledge about epilepsy upside down.

How the brain works and seizures originate

The brain is an accumulation of a myriad of nerve cells that are connected with an equal number of nerve fibers.

The communication from one end of the brain to the other end occurs via electrical signals. They have their origin in the nerve cells and travel through the nerve fibers at an astonishingly fast rate.

The nerve cells of the brain also have a connection to the muscles, organs and skin. This is achieved with the help of nerve fibers. They travel through the spinal cord and peripheral nerves to reach the end organs. Again the transmission of these communication signals are through electrical impulses. Usually these signals are perfectly balanced by inhibitory nerve cells, whose job it is in the spinal cord and throughout the brain to keep these electrical signals under control.

Unfortunately some people are not so lucky. They have a “low seizure threshold” and a fever or stress can trigger a seizure or epilepsy. This is a state of the brain where activated parts are overruling the inhibitory parts and an epileptic seizure or partial seizure results. In the case of a grand mal seizure the person may be unconscious for a brief period of time while the muscles have shaking spells. It may start with involuntary muscle twitching around the eyes, the patient becomes unconscious and may fall down onto the ground. The patient may bite the tongue, stop breathing, shake arms, then the trunk muscles and finally both legs. Around 1 in 100 people get epilepsy, and it is mostly children and people above the age of 65 who get it.

New research regarding two proteins responsible for getting epilepsy

Rochelle Hines led a team of neuroscientists from the University of Nevada, Las Vegas in this research. They investigated two proteins involved in inhibiting the central nervous system. In the past it was thought that an overstimulation of nerve cells would have caused electrical overstimulation of the central nervous system causing epilepsy. Now this new research showed that it is two proteins that are missing. Normally these proteins suppress the electrical nerve activity that leads to epilepsy.

First of all, gephyrin is a protein that regulates GABA receptors. GABA is a brain hormone that calms the brain. Another protein, called collybistin is a regulator of the localization of gephyrin.

Different approach to study epilepsy will find better medications

Rochelle Hines and her team found two key proteins, gephyrin and another protein, the alpha-2 subunit of the GABA receptor. They found that they have to interact with each other in order to calm the brain. If this does not occur, seizures (epilepsy) can occur. The emphasis of this research was on finding ways to stimulate the inhibition of the GABA receptor system. In the past the emphasis was to generally calm down the entire brain with medications. This caused a lot of side effects because the traditional anti-seizure medications do not target a specific area of the brain. Now scientists can work with the two key inhibitory proteins, gephyrin and the alpha-2 subunit of the GABA receptor. At this point a new medication is not yet available, but certainly when the development of it is complete, it will be more specific and have fewer side effects.

Some citations from the lead researcher, Rochelle Hines

“Regulating this ‘compartment’ of proteins in the brain that controls cell signalling may lead to better therapies for stopping or preventing seizures. If we can better understand the activity of the brain pattern, we can understand how it might go wrong in a disorder like epilepsy, where brain activity becomes uncontrolled. And if we can understand what is important for this control, we can come up with better strategies for treating and improving the quality of life for people with epileptic seizures and maybe other types of disorders as well, such as anxiety or sleep disorders.”

It is interesting to me that seizures and anxiety maybe the same process in the brain. While with anxiety the brain is irritated, it is still controlled. In contrast in the case of epilepsy the control of the GABA system is gone and the brain excitation is uncontrolled. Medication that will increase the proteins gephyrin and the alpha-2 subunit of the GABA receptor is badly needed.

Two Proteins Responsible For Getting Epilepsy

Two Proteins Responsible For Getting Epilepsy

Conclusion

Epilepsy and seizure disorders appear to now be due to a lack of inhibition in the central nervous system. Two proteins that work on the inhibitory GABA receptors hold the key. They are gephyrin and the alpha-2 subunit of the GABA receptor. There are mouse strains that are deficient for these proteins, and they come down with epilepsy. The human brain has the same proteins that are necessary to inhibit the brain. In anxiety disorders it seems like there is a mild loss of these inhibitory proteins. In contrast with epilepsy the deficiency of these hormones is more severe. Researchers are now concentrating on developing new drugs or modifying existing drugs to stimulate the production of these inhibitory proteins. The hope is that these medications will have fewer side effects, because they will be more receptor specific.