The Medication Question

As you may know, medications are the backbone of the Parkinson's treatment plan. But because the disease affects everyone differently, and each person's response to therapy will vary, there is no hard-and-fast rule about when you should begin taking medication and what to take first. Some doctors prescribe medication upon diagnosis. Others believe that drugs, especially levodopa, should be delayed as long as possible to avoid earlier onset of medication-related side effects.

Your involvement from the very start is important because you want to be sure your doctor is addressing your individual needs. When your doctor writes a new prescription, or makes a change to an existing one, take the opportunity to ask for an explanation. If her response goes something like, "I always start my Parkinson's patients on X dosage of Y, a dopamine agonist," you might want to consider switching to a movement disorders specialist, a neurologist who has had special training in Parkinson's disease and other movement disorders.

Taking a closer look at your options

Since the drug levodopa (L-dopa for short) was synthesized in the 1960s, levodopa in combination with carbidopa (brand name Sinemet), has been the gold standard for treating the symptoms of Parkinson's. However, after several years of taking this medication some people experience dyskinesias, or involuntary writhing movements. This is sometimes referred to as levodopa-induced dyskinesias or "LIDS." The fear of these side effects has led many clinicians and patients to avoid levodopa-carbidopa for as long as possible.

But some experts do not believe this "levodopa phobia" is warranted (risk factors for LIDS include younger age at onset, duration of treatment and a higher levodopa dose). In short, they say that levodopa can be considered as a potential first-line therapy in all age groups---although caution should be exercised in younger patients. In most cases, the dosage will start low then increase slowly, often in combination with other medications, to adjust to a person's changing condition.

Other first-line medications that can be used to control Parkinson's symptoms include drugs known as dopamine agonists and monamine oxidase inhibitors. Dopamine agonists provide relief by mimicking the action of dopamine within the brain, and monamine oxidase inhibitors help maintain motor control by slowing the breakdown of dopamine within the brain. These drugs can help younger patients buy some time before starting levodopa-carbidopa.

For an in-depth explanation of all medications used to treat both motor and non motor symptoms of Parkinson's disease medications, download a copy of NPF's Parkinson's Disease Medications Manual.

Timing is everything

When it comes to Parkinson's medications, timing is critical. That is why it is so important to take all prescription drugs exactly as directed. Levodopa-carbidopa, in particular, must be taken in precise, consistent dosages throughout the day in order to control symptoms. The goal is to maintain a steady supply of the medicine in your bloodstream. When medication is not taken on time, "freezing" and other sudden and debilitating motor symptoms can occur.

Keeping a drug diary

You will need to report back to your doctor about how your body is responding to the medication you are taking. A good way to do this is by keeping a drug diary. This can be done simply, with a notebook and a pencil. Take this diary with you to every doctor visit. Here is what to record:

Warning signs. Write down any new experience, from a headache to mild diarrhea to hives to anaphylactic shock. Ask your care partner to jot down any side effects he or she notices.

Changes to your meds. Whenever your doctor adds or withdraws a medication or changes a dose, enter that information into your diary.

A list of medicines. Keep an updated list of everything you are taking, including supplements, along with specific dosages.

Avoiding negative interactions

Be aware that some medicines can have a negative effect on your condition. That is why it is important to familiarize yourself with all the medications that people with Parkinson's should avoid. Having this information on hand can help prevent dangerous interactions and other problems.

As you can see the answer to the medication question can be long and and tricky. Work with your physician to make sure you are taking the medications that are right for you.

by Jackie Hunt Christensen

Too much protein may kill brain cells as Parkinson’s progresses

 Follow NINDSnews 

For release: Thursday, April 10, 2014

NIH-funded study on key Parkinson’s gene finds a possible new target for monitoring the disease

Parkinson’s killer lurks 
within

NIH-funded scientists show that the deadly Parkinson’s gene LRRK2
can kill nerve cells (green) by 
tagging the s15 ribosomal protein (purple), a cog in a cell’s 
protein-making machinery. 
Courtesy of Dawson lab, JHU 
Morris K. Udall Center of 
Excellence for Parkinson’s Disease.

Scientists may have discovered how the most common genetic cause of Parkinson’s disease destroys brain cells and devastates many patients worldwide.  The study was partially funded by the National Institutes of Health’s National Institute of Neurological Disorders and Stroke (NINDS); the results may help scientists develop new therapies.

“This may be a major discovery for Parkinson’s disease patients,” said Ted Dawson, M.D., Ph.D., director of the Johns Hopkins University (JHU) Morris K. Udall Center of Excellence for Parkinson’s Disease, Baltimore, MD.  Dr. Dawson and his wife Valina Dawson, Ph.D., director of the JHU Stem Cell and Neurodegeneration Programs at the Institute for Cell Engineering, led the study published in Cell.

The investigators found that mutations in a gene called leucine-rich repeat kinase 2 (LRRK2; pronounced “lark two” or “lurk two”) may increase the rate at which LRRK2 tags ribosomal proteins, which are key components of protein-making machinery inside cells. This could cause the machinery to manufacture too many proteins, leading to cell death. 

“For nearly a decade, scientists have been trying to figure out how mutations in LRRK2 cause Parkinson’s disease,” said Margaret Sutherland, Ph.D., a program director at NINDS. “This study represents a clear link between LRRK2 and a pathogenic mechanism linked to Parkinson’s disease.”

Affecting more than half a million people in the United States, Parkinson’s disease is a degenerative disorder that
 attacks nerve cells in many parts of the nervous system, most notably in a brain region called the substantial 
nigra, which releases dopamine, a chemical messenger important for movement. Initially, Parkinson’s disease
 causes uncontrolled movements; including trembling of the hands, arms, or legs. As the disease gradually 
worsens,
 patients lose ability to walk, talk or complete simple tasks.

For the majority of cases of Parkinson’s disease, a cause remains unknown. Mutations in the LRRK2 gene are a 
leading genetic cause. They have been implicated in as many as 10 percent of inherited forms of the disease 
and in aboutt 4 percent of patients who have no family history. One study showed that the most common LRRK2 mutation, called G2019S, may be the cause of 30-40 percent of all Parkinson’s cases in people of North 
African Arabic descent.

LRRK2 is a kinase enzyme, a type of protein found in cells that tags molecules with chemicals called phosphate 
groups. The process of phosphorylation helps regulate basic nerve cell function and health. Previous studies 
suggest that disease-causing mutations, like the G2019S mutation, increase the rate at which LRRK2 tags
 molecules. Identifying the molecules that LRRK2 tags provides clues as to how nerve cells may die during 
Parkinson’s disease.

In this study, the researchers used LRRK2 as bait to fish out the proteins that it normally tags.  Multiple
 experiments performed on human kidney cells suggested that LRRK2 tags ribosomal proteins. These proteins
 combine with other molecules, called ribonucleic acids, to form ribosomes, which are the cell’s protein-making
 factories. 

Further experiments suggested that disease-causing mutations in LRRK2 increase the rate at which it tags two ribosomal proteins, called s11 and s15. Moreover, brain tissue samples from patients with LRRK2 mutations 
had greater levels of phosphorylated s15 than seen in controls.

Next, the researchers investigated whether phosphorylation could be linked to cell death, by studying nerve cells 
derived from rats or from human embryonic stem cells. Genetically engineering the cells to have a LRRK2 mutant
 gene increased the amount of cell death and phosphorylated s15.  In contrast, the researchers prevented cell death
 when they engineered the cells to also make a mutant s15 protein that could not be tagged by LRRK2. 

“These results suggest that s15 ribosome protein may play a critical role in the development of Parkinson’s 
disease,” said Dr. Dawson.

How might phosphorylation of s15 kill nerve cells? To investigate this, Dr. Dawson and his colleagues performed experiments on fruit flies. 

Previous studies on flies showed that genetically engineering dopamine-releasing nerve cells to overproduce 
the LRRK2 mutant protein induced nerve cell damage and movement disorders. Dr. Dawson’s team found that
 the brains of these flies had increased levels of phosphorylated s15 and that engineering the flies so that s15 
could not be tagged by LRRK2 prevented cell damage and restored normal movement. 

Interestingly, the brains of the LRRK2 mutant flies also had abnormally high levels of all proteins, suggesting that increased s15 tagging caused ribosomes to make too much protein. Treating the flies with low doses of 
anisomycin, a drug that blocks protein production, prevented nerve cell damage and restored the flies’ movement
t even though levels of s15 phosphorylation remained high.

“Our results support the idea that changes in the way cells make proteins might be a common cause of Parkinson’s disease and possibly other neurodegenerative disorders,” said Dr. Dawson.

Dr. Dawson and his colleagues think that blocking the phosphorylation of s15 ribosomal proteins could lead to
 future therapies as might other strategies which decrease bulk protein synthesis or increase the cells’ ability to 
cope with increased protein metabolism. They also think that a means to measure s15 phosphorylation could also
 act as a biomarker of LRRK2 activity in treatment trials of LRRK2 inhibitors.

This work was supported by grants from the NINDS (NS038377, NS072187), the JPB Foundation, the Maryland
 Stem Cell Research Fund (2007-MSCRFI-0420-00, 2009-MSCRFII-0125-00, 2013-MSCRFII-0105-00), and
 the New York Stem Cell Foundation.

References:

Martin et al. “Ribosomal protein s15 phosphorylation mediates LRRK2 neurodegeneration in Parkinson’s
 disease,” Cell, April 10, 2014. DOI: 10.1016/j.cell.2014.01.064

For more information about Parkinson’s disease, please visit:

http://www.ninds.nih.gov/disorders/parkinsons_disease/parkinsons_disease.htm

###

NINDS (http://www.ninds.nih.gov) is the nation’s leading funder of research on the brain and nervous system. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease. 

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 
Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the
 primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about 
NIH and its programs, visithttp://www.nih.gov.

Last Modified June 10, 2014

Dopamine in action

Everything You Need to Know About Dopamine Receptors in 5 Easy Minutes

STUDY: GMO FREE USA: ROUND-UP Causes Toxic Damage To Rat Brains

GMO Free USA with Rick Tallman and 3 others

STUDY: Roundup Herbicide Causes Toxic Damage to Rat Brains. The summarization of their results, looking at the effects of both acute and chronic exposure, werereported as follows: "Taken together, these results demonstrated that Roundup might lead to excessive extracellular glutamate levels and consequently to glutamate excitotoxicity and oxidative stress in rat hippocampus." The hippocampus processes memories, emotional responses and more. This leads us to ask... what health problems might be caused by Roundup induced toxicity to the human brain as a result of the Roundup laden GMOs in our food? 

Please watch video:
https://www.youtube.com/watch?feature=player_embedded&v=Njd0RugGjAg

Parkinson’s Personality

Posted on June 7, 2012 by rickderlis

Parkinson’s Personality: Disease More Likely to Strike Cautious People

By Rachael Rettner, MyHealthNewsDaily Staff Writer | LiveScience.com – Tue, May 1, 2012

Some personality traits appear to be linked with the risk of developing Parkinson’s disease, a new study suggests.

The results show patients with Parkinson’s disease are more likely to be cautious and avoid taking risks compared with people who don’t have Parkinson’s.

Moreover, the tendency to avoid taking risks appears to be a stable personality trait across a patient’s lifetime — as far back as 30 years before symptoms began, those with Parkinson’s disease said they did not often engage in risky or exhilarating activities, such as riding roller coasters or speeding, the study found.

The findings add to a growing body of research suggesting Parkinson’s is more likely to afflict people with rigid, cautious personalities.

It’s possible that what we consider to be aspects of someone’s personality may in fact be very early manifestations of Parkinson’s, said study researcher Kelly Sullivan, of the University of South Florida’s department of neurology. However, much more research is needed to confirm this hypothesis, Sullivan said.

It’s also way too soon to say that having a “look before you leap” personality puts you at risk for Parkinson’s.

“I’m not a big risk-taker, but at the same time, I haven’t resigned myself that I’m going to have Parkinson’s,” Sullivan said.

Parkinson’s personality

Since the early 1900s, there have been reports that Parkinson’s patients tend to be industrious, punctual, cautious and risk-averse. Most studies that have found a link between Parkinson’s and a risk- avoidant personality have been based on assessments of patients’ personalities prior to the disease, using questions such as “did you take risks when you were younger?” However, remembering what you were like many years ago may be difficult, and what someone considers a “risk” is subjective, Sullivan said.

In the new study, Sullivan and colleagues asked 89 patients with Parkinson’s and 99 healthy people whether they engaged in specific activities— such as riding roller coasters, speeding and wearing a seatbelt— before the age of 35.

They also asked questions to gauge participants’ current personalities.

The results showed that participants with Parkinson’s had higher levels of neuroticism — a personality trait associated with experiencing more negative emotions such as anxiety — and higher levels of harm-avoidance compared with healthy participants. In general, participants’ willingness to take risks tended to be stable over time, and Parkinson’s patients tended to report they took fewer risks.

Another study by Sullivan and colleagues found women with Parkinson’s disease were 60 percent more likely to say they had a routine lifestyle as a young adult (such as getting up and going to bed at the same time every day) compared with people without Parkinson’s.

Too little dopamine

A brain chemical called dopamine is needed to control muscle movement, and in Parkinson’s disease patients, the brain cells that produce dopamine start to die. This cellular death leads to the tremors and difficulty with walking, movement and coordination, which are hallmarks of Parkinson’s.

Levels of dopamine may also affect personality. Dopamine is responsible for signaling 
feelings of reward and pleasure. “When you take a risk or jump out of an airplane, that’s 
what gives you that reward feeling,” Sullivan said.

“If you have lower levels of dopamine, it’s less likely that you would really get that neurochemical reward and say ‘That was awesome! Let’s keep doing that,’” Sullivan said.
While the symptoms of Parkinson’s don’t show up until about 70 percent of dopamine-producing cells have deteriorated, Sullivan said, it’s possible the loss of
dopamine-producing cells goes on for a long period before someone is diagnosed, 
Sullivan said.

More research is needed to know exactly how long this process of brain cell loss goes on,
 and whether the risk-avoidant behaviors exhibited early in life by Parkinson’s patients 
are actually manifestations of the disease, Sullivan said.

Sullivan’s studies were presented last week at the American Academy of Neurology 
meeting in New Orleans.

Pass it on: Parkinson’s diseases patients tend to have more cautious personalities.

Topping the function of a protein called LRRK2

The Michael J. Fox Foundation for Parkinson's Research shared a link.

5 hours ago

Stopping the function of a protein called LRRK2 may help treat all people with Parkinson’s disease, even those without a LRRK2 genetic mutation.

Study Shows Promise for Parkinson’s Disease Treatment Approach

www.michaeljfox.org

The next step is to try and replicate results with a drug that can go to clinical trial.

Is Roundup Weedkiller A Brain-Damaging Neurotoxin?

Friday, March 21st 2014 at 5:45 am

Written By: 

Sayer Ji, Founder

A new study reveals a hitherto unknown mechanism behind how the world's most popular GMO herbicide harms the brain.
Remarkably, despite Roundup^® herbicide's widespread approval around the world, the most basic mechanisms through which it exerts toxicity towards non-target animal species (including humans) have yet to be adequately characterized.
Concerned about Brazil's status as the largest global consumer of pesticides since 2008, researchers sought to elucidate toxicologic effects of these agrochemicals in humans.
Their new study, published in the journal Toxicology, provides a proposed mechanism for the adverse neurological effects of Roundup^® (a glyphosate-based herbicide).  It is has been observed that agrochemical exposure can lead to, or accelerate, neurodegenerative disorders, such as Parkinson's and Alzheimer's disease. However, lacking a mechanism of action, such a link can more easily be written off as coincidental; which is largely the position of the medical establishment, agricultural industry, and its would-be regulators. The authors point out that, "neurodegenerative conditions are frequently associated with glutamatergic excitotoxicity and oxidative stress," which is why they decided to investigate the subject further.
Titled, "Mechanisms underlying the neurotoxicity induced by glyphosate-based herbicide in immature rat hippocampus: Involvement of glutamate excitotoxicity,"[i] the paper tested the neurotoxicity of Roundup® in the hippocampus of immature rats following acute exposure (30 minutes) and chronic (pregnancy and lactation) exposure.
The results found that acute exposure to Roundup^® induces calcium influx into neurons (primarily, by activating NMDA receptors and voltage-dependent Ca²⁺ channels), leading to oxidative stress and neural cell death. They also found that the herbicide affected the enzymes ERK and CaMKII, the later of which is an enzyme whose dysregulation has been linked to Alzheimer's disease.[ii] Additionally, acute exposure was observed to have the following three effects:

1. Increase the amino acid glutamate into the junctions through which neurons communicate (synaptic cleft), which, when released in excess levels, can exert excitotoxic/neurotixc effects in neurons.
2. Decrease the neuroprotective antioxidant glutathione.
3. Increase 'brain rancidity,' i.e. lipoperoxidation, characterized by excitotoxicity (over-stimulation of the neurons) and oxidative damage.

The summarization of their results, looking at the effects of both acute and chronic exposure, were reported as follows:

"Taken together, these results demonstrated that Roundup^® might lead to excessive extracellular glutamate levels and consequently to glutamate excitotoxicity and oxidative stress in rat hippocampus."

Roundup-induced glutamate excitotoxicity appears to share similar effects to monosodium glutamate (MSG) and aspartame-linked excitotoxicity, and indicating that anyone either prone to, or suffering from, a brain or neurological condition involving increased oxidative stress and/or neuronal excitotoxicity (pathological or excessive nerve cell stimulation) should be even more wary to reduce exposure to this unfortunately ubiquitous environmental and food contaminant.
The authors also pointed out that their study found maternal exposure to Roundup^® resulted in the offspring being exposed to the herbicide because it crosses the placental barrier during gestation and/or it is passed to them through the breast milk. They caution:

"Exposure to environmental toxicants during pregnancy and suckling periods has the potential to affect embryo and fetal development."

This is not the first time that concerns have been raised about Roundup's unique contraceptiveand birth defect causing properties.
For additional information on the adverse effects of Roundup herbicide and related glyphosate formulations, visit our database sections on the topic, which references peer-reviewed and published research from the National Library of Medicine on the chemical.

• Roundup herbicide
• Glyphosate formulations

Also, dig deeper into the non-safety of GMO farming, food and environmental and health consequences, by visiting our GMO research center.

---

[i] Daiane Cattani, Vera Lúcia de Liz Oliveira Cavalli, Carla Elise Heinz Rieg, Juliana Tonietto Domingues, Tharine Dal-Cim, Carla Inês Tasca, Fátima Regina Mena Barreto Silva, Ariane Zamoner.MECHANISMS UNDERLYING THE NEUROTOXICITY INDUCED BY GLYPHOSATE-BASED HERBICIDE IN IMMATURE RAT HIPPOCAMPUS: INVOLVEMENT OF GLUTAMATE EXCITOTOXICITY. Toxicology. 2014 Mar 14. Epub 2014 Mar 14. PMID: 24636977

[ii] Yamauchi, Takashi (August 2005). "Neuronal Ca2+/calmodulin-dependent protein kinase II—discovery, progress in a quarter of a century, and perspective: implication for learning and memory".Biological & Pharmaceutical Bulletin 28 (8): 1342–54. doi:10.1248/bpb.28.1342. PMID 16079472.

Emotional Responses to Parkinson's Disease

When you or a family member is first diagnosed with PD you will most likely go through a host of emotions. For most people, a diagnosis can feel devastating. The first concern is whether PD will interfere with the life they currently lead or plans for the future. They may imagine the future and think about whether they will be able to walk, talk, eat or take care of themselves, let alone take care of or provide for their families.  It is important to remember that everything you are feeling is normal. In fact, there are stages of adjustment to PD. Each individual may experience any or all of these typical phases and may not progress through them in any particular time or order. The stages are as follows:

Denial

• This response may be prolonged if symptoms are mild or the correct diagnosis is not made early in the course of the disease.
• Ironically, denial can be a useful coping mechanism if it allows one to largely ignore symptoms and go on with life as usual. 
• However, if a person refuses to take medication, or goes to extremes seeking second opinions, it may indicate denial as an unhealthy response.

Discouragement

• In this phase, people look for some direct cause for the health problems they are experiencing.
• They become preoccupied with the why me question, while searching for something or somebody to blame for the unwanted circumstances occurring in their lives.

Role Conflict

• This happens when patients and care partners become confused and frustrated with the daily fluctuations in symptoms, and when the need arises to reevaluate who is responsible for what tasks in the family.
• Changing abilities and assuming new roles within the family can cause emotional upheaval. 
• A family coping with these issues often benefits from meeting with a counselor and dealing openly with these conflicts.

Identity Change

• In this stage, people realize that life has changed and become willing to seek out others with the same condition for education and encouragement and to take on the work of achieving their optimal level of independence.

Adaptation

• In this stage, patients exert a degree of control over their illness by assuming an active role in their health care; for example, working with their doctor to choose what medications to take and in what doses.

• Medical content reviewed by: Nina Browner, MD—Medical Director of the NPF Center of Excellence at the University of North Carolina at Chapel Hill in North Carolina and by Fernando Pagan, MD—Medical Director of the NPF Center of Excellence at Georgetown University Hospital in Washington, D.C.

Dealing with Changes in Your Relationships

Jackie Hunt Christensen

How to Improve Communication After a Parkinson’s Diagnosis

Clearly, all of us are born to connect. And, not surprisingly, our facial expressions and voice have a big impact on our ability to communicate with others. For example, having a strong, expressive voice is generally seen as a sign of power, while being soft-spoken is often equated with timidity. Consider the following scenario. A woman who was once assertive and competitive in the workplace can no longer motivate her employees with impassioned pep talks. As a result, she loses confidence in herself and believes she no longer measures up. Her performance suffers and she resigns from her position. This scenario illustrates how facial masking, or the blank-like expression due to rigid muscles, and a soft, “flat” voice can deal quite a blow to a person’s identity. Unfortunately, these symptoms of Parkinson’s disease can bring about major changes in the roles of relationships. Please bear in mind, however, that while you will likely face these challenges at some point, it is still possible to maintain meaningful, productive relationships. To do so, you will need to address the issues that affect your ability to communicate effectively with the people in your life.

Changing Roles in the Family

If you are having masking and speech issues early on, it is a good idea to plan for a time when you may need someone else to speak on your behalf. If you do not have a spouse or partner to assist you, you may have to turn to one of your children or grandchildren. It is imperative to find someone you trust, because the truth is that there are family members who will misrepresent the wishes of a loved one for whom they are caring. Helping friends understand At some point, you will need to have an honest conversation with your friends about your Parkinson’s disease. Try to maintain connections with upbeat people who understand your condition and are willing to learn more and perhaps even lend a hand when needed. But do not be surprised to learn that not everyone is willing to be in your company when your symptoms worsen. In the workplace If you have a position that requires a lot of interaction with other people, you will be under extra stress if you try to hide your disease from them. More importantly, if your speech is affected, others may think that you are drunk or on recreational drugs. If you want to learn about accommodations you can request from your employer or you believe that you are being discriminated against, you might want to consult with an attorney that specializes in disability law or go to the American with Disabilities Act website at www.ada.gov

Singles Face Unique Challenges

Remember, when it comes to dating and building new friendships, this can be difficult for anyone, let alone for someone living with Parkinson’s disease. Body language and facial expressions are usually the first things on which we are judged. Here are some places where you might find people who will be more understanding:

• Support groups. This is not limited to Parkinson’s groups. Many cities have groups for people with chronic illnesses.
• Your doctor’s office. Chances are very good that the people in the waiting room can understand your battles with Parkinson’s. You can become a source of encouragement and support for others as well as receive it.
• Your place of worship. You could find a sense of belonging and community.
• Local Parkinson’s organizations. Attending events or volunteering will help you form tight social bonds.
• Internet chat rooms and forums. Many single people with Parkinson’s disease have built strong friendships through virtual communities on the Internet.
• Parkinson’s exercise classes.

Finally consider this: most likely your relationships with your loved ones will have some change... however; the change may be for good.