Don’t Worry, Be Happy: Parkinson’s and the Limits of Positive Thinking

worry

I don’t want to take away from Mad magazine’s Alfred E. Neuman or singer-songwriter Bobby McFerrin, but the idea that a pair of rose-colored “don’t worry” glasses will change my life for the better has never sat well with me. Pollyanna is not a guest in my home.

“Look at all the wonderful things in your life. All your needs are provided for — no worries,” someone said to my wife and me recently as we described the temporary ruin of stagnation. But pouring saccharin sentiments over the burnt toast of my life won’t remove its acrid flavor.

I often write about having a positive action-based wellness plan. My approach is attitude plus behavior equal consequences. My positive outlook is wisdom-based and engaged in compassion and not on my ability to see a half-full glass. One can try to view the chronic disease glass as being half full, but the reality is that it is also half empty. I wish that my muscular problems and other Parkinson’s symptoms were absent. Viewing the glass as half full is not an action plan — it’s more of an “I’m tired of this right now” statement.

Many authors have extolled positive thinking: Norman Vincent Peale and Norman Cousins, among others. Choosing how to act, think, and feel creates patterns. We return to those patterns when times get tough. Another way of putting it is, “Fake it until you make it.” It seems vacuous to assume that “faking” happiness will remove the causes of unhappiness or make circumstances appear to be better than they are. Well-meaning people who propose the “don’t worry, be happy” solution don’t have a clear understanding of how Parkinson’s and other chronic diseases affect our daily lives. What we need is a well-designed and enacted wellness map — not rose-colored glasses.

Though my partner and I have moments of frustration and utter despair, we manage to pull ourselves up — as we have throughout our lives — to find the inner and spiritual strength that enables us to continue. It’s a lifelong habit for both of us, and as a team, we support each other through the continued challenges, taking turns with compassion and strength when the other one falters under the burden.

Do we worry? Yes, but we move gradually toward more acceptance. Are we happy? The glass remains half full, and we are grateful for the happiness and blessings in our lives. But it is now time to replenish the glass and move into deeper compassion, finding strength in the belief that all things happen for a reason and in their own time. We will not shy away from the work that needs to be done in our lives and for others with chronic diseases.

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Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.

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SleepFit App Can Help Improve Daily Monitoring of Parkinson’s Motor Symptoms, Study Says

SleepFit monitor motor, Parkinson's

A new application for Android tablets, called SleepFit, may help to monitor the daily progression and response to treatment of motor symptoms associated with Parkinson’s disease, according to a study.

The application was evaluated in the study “A New Prospective, Home-Based Monitoring of Motor Symptoms in Parkinson’s Disease,” which was published in the Journal of Parkinson’s Disease.

Development and approval of new therapies for Parkinson’s disease has made it possible for many patients to retain a relatively active lifestyle. However, therapies do not have the same effect on all patients, so doses and treatment regimens need to be tailored to each patient’s needs.

In routine clinical practice, adjusting antiparkinsonian therapy relies on a combination of objective evaluation of symptoms and subjective analysis of the patient’s perspectives and experiences.

Clinicians have several clinical assessment tools to help evaluate the progression of Parkinson’s symptoms, including the Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), which is commonly used to assess motor skills and symptoms.

Reviewing a patient’s perspectives and experiences can, in contrast, be a challenge rather than a helpful strategy. Some patients show subclinical cognitive dysfunction, even at early stages of the disease, which can impact the way they perceive their symptoms and surrounding environment.

“The importance of accurately assessing motor symptoms is pivotal in the clinical follow-up of patients with [Parkinson’s disease],” Pietro Luca Ratti, MD, PhD, researcher at the Neurocenter of Southern Switzerland, in Switzerland, and lead author of the study, said in a press release.

“In fact, physicians’ therapeutic decisions rely on the subjective information provided by a patient just as much as on the physical examination,” he added. “This is particularly important considering that antiparkinsonian medications need to be prescribed at their minimal effective doses to optimize mobility, while minimizing undesirable side effects.”

To inform clinical decision-making, researchers have developed SleepFit, an easy-to-use application (app) for Android tablets that can help patients record of their motor symptoms at given times of the day.

Using questions and tests to collect data on the patient’s motor and mobility skills, the app can be a source of subjective data that’s unbiased by patient recall. It integrates the items measuring motor symptoms from the Scales for Outcome in Parkinson Assessment Diary Card (m-SCOPA-DC) and a new Visual Analogue Scale assessing global mobility (m-VAS).

Researchers evaluated the potential of this new home-based tool and compared it to data collected from standard interviews among 42 patients with mild to moderate Parkinson’s who participated in the Sleep and Move study (NCT02723396).

All participants were asked to use the app four times a day for 14 days to record their symptoms: in the morning, 30 minutes after waking up and one hour after intake of dopaminergic medication; in the afternoon before taking dopaminergic medication; and in the evening before bedtime.

On the last day, patients completed the MDS-UPDRS parts II and IV questionnaires during an office consultation in order to assess their subjective recall of motor symptoms.

In general, data collected through the two methods showed similar results for overall scores, with m-VAS scores differing by 10% and SCOPA-DC by 18.3%. For single motor symptoms, such as involuntary movements, hand dexterity, walking, and ability to change position, results were also similar with differences of less than 20% between the two methods.

However, some individuals with more advanced disease, higher fatigue, or worse sleep quality had more difficulty recalling their symptoms.

Evaluation of patients’ self-reported information did not reveal a tendency towards positive or negative thinking about their symptoms. Still, 16.7% of the participants did tend to over- or underestimate their symptoms in their recollection.

“Knowing of a given patient’s tendency towards positive or negative thinking could thus critically inform clinical decision-making with regard to dopaminergic medication adjustment,” the researchers wrote.

These preliminary results demonstrate that the SleepFit app could be useful in routine clinical practice to reduce retrospective self-reporting bias, particularly for patients who have more advanced disease or cognitive impairments.

“We believe that a prospective approach would enable better clinical evaluation of patients’ subjective symptoms and, thus, better clinical management of the patients themselves,” said Ratti, who is also a researcher at the Pierre Zobda-Quitman University Hospital in Fort-de-France, Martinique.

“Although SleepFit is still under development, we believe it will eventually become a powerful tool to support patient evaluation in real-life conditions, encompassing motor and non-motor symptoms of [Parkinson’s disease],” he said.

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Parkinson’s Foundation Grants $250K for Parkinson’s UK Treatment Project

Parkinson’s Foundation

As part of a new partnership with Parkinson’s UK, the Parkinson’s Foundation has granted the nonprofit $250,000 toward a prospective new treatment linked to mitochondrial function that is being developed in the Parkinson’s Virtual Biotech program.

The grant will help advance a project aimed at uncovering new methods of potentially impeding brain cell death through stabilization of the source of energy necessary for cell survival — the mitochondria. It’s the first international funding for the Parkinson’s UK-led program and marks the beginning of a collaborative effort to move forward promising Parkinson’s (PD) treatment research.

“We are pleased to partner with Parkinson’s UK to further innovative research that will help the international PD community,” John Lehr, president and CEO of the Parkinson’s Foundation, said in a press release. “This collaboration will help us better serve people living with Parkinson’s today while furthering the promise of a cure tomorrow.”

Parkinson’s UK and its supporters and collaborators each year invest more than $5 million in Parkinson’s Virtual Biotech — the organization’s drug discovery and development arm — focusing on projects with the potential to transform patients’ lives. Fueled by project-specific partnerships with some of the world’s top research organizations, the program’s goal is to invest $29 million by the end of 2021.

“We are delighted to receive this investment from the Parkinson’s Foundation to support a growing portfolio of projects in our Virtual Biotech,” said Steve Ford, chief executive of Parkinson’s UK. “While we have made huge strides in our research efforts, we have long recognized that we can’t do it alone. The Parkinson’s Foundation shares this philosophy that we’re better together, and their investment marks a new chapter that will help ensure the Parkinson’s community receives the new treatments it needs.”

With its grant, the Parkinson’s Foundation is focusing on a £98,000 (about $126,000) year-long project with the University of Sheffield that began in August called “Novel Mitochondrial Rescue Compounds.”

Through compound modification, scientists will seek to discover and develop a potential therapy that could protect the dopamine-producing brain cells affected by Parkinson’s. The hope is that the most promising study compound ultimately will result in prospective brain cell-protecting treatments that could slow PD progression and enhance patients’ lives.

Parkinson’s is caused by the death or malfunction of dopaminergic neurons, which regulate muscle movement and coordination. To do their job, these nerve cells require large amounts of mitochondra-provided energy. Studies have widely suggested that mitochondrial dysfunction plays a central role in the development of PD.

To date, the Parkinson’s Virtual Biotech program has invested in seven drug discovery and development projects.

In addition to this collaboration, the two PD organizations also are working together on Parkinson’s Revolution, an indoor cycling fundraiser slated for Feb. 8 across the United States, the United Kingdom and Canada. The event is designed to highlight the benefits of exercise in PD while also raising funds for research and programs.

Since 1957, the Parkinson’s Foundation has invested more than $353 million in PD research and clinical care. Parkinson’s UK is Europe’s largest charitable funder of Parkinson’s research.

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Way of Monitoring Stem Cells Maturing in Nerve and Other Cells May Aid Parkinson’s Understanding, Treatment

stem cells and disease

A new biosensor system may make it easier to monitor stem cells changing into mature cells like neurons, which could allow for a better understanding of diseases like Parkinson’s and support the development of new treatments.

The system was described in the paper, “Dual-Enhanced Raman Scattering-Based Characterization of Stem Cell Differentiation Using Graphene-Plasmonic Hybrid Nanoarray,” published in Nano Letters.

Stem cells are able to continuously divide and to differentiate into other types of cells. Because of these properties, stem cells have gained interest in a number of fields, including regenerative medicine for neurological conditions like Parkinson’s and Alzheimer’s. The basic idea is that they could be used to ‘replace’ brain cells (neurons, a type of nerve cell essential for cell-to-cell communication) that become damaged in the course of the disease.

However, applications like this would require exquisitely precise monitoring of these cells.

“A critical challenge is ensuring high sensitivity and accuracy in detecting biomarkers — indicators such as modified genes or proteins — within the complex stem cell microenvironment,” KiBum Lee, MS, PhD, a study co-author and professor at Rutgers University, said in a press release. “Our technology, which took four years to develop, has demonstrated great potential for analyzing a variety of interactions in stem cells.”

The new technology relies on a technique called Raman spectroscopy. In simple terms, this technique involves analyzing the way light scatters off of molecules, which — with the help of computational analyses — allows scientists to figure out details about the molecules being studied.

The signals generated by Raman spectroscopy are, by their very nature, tiny. In essence, the new system uses a combination of gold nanostructures and very thin layers of graphene to amplify these signals, a technique called surface-enhanced Raman scattering (SERS).

By analyzing what molecules a cell is making, particularly in terms of RNA, researchers can gain insight into what genes in a cell are ‘on’ or ‘off’ (gene expression), which is critical for understanding the development of stem cells.

Of note, gene expression is the process by which information in a gene is synthesized to create a working product, like a protein.

As a proof-of-concept, the researchers analyzed neural stem cells, a specific subset of stem cells that, as their name suggests, can differentiate into neurons. They confirmed that their system showed that the pre-differentiation stem cells had high expression of the stem cell marker Nestin, whereas cells that differentiated into neurons had high expression of a neuron marker called TuJ1 (class III β-tubulin).

“Utilizing our developed system we can confirm approximately 2 orders of magnitude increase in Tuj1 RNA level [in differentiated cells],” the researchers wrote. Importantly, this finding was consistent with the results of analysis with polymerase chain reaction (PCR), which is a well-established technique for measuring RNA levels and, by extension, gene expression.

“Collectively,” the researchers concluded, “we believe that our graphene−Au [gold] hybrid SERS nanoarray system will not only be used for high-quality and high throughput bio/chemical molecule screening assays but will also help us to understand cellular phenomena such as disease progression and stem cell differentiation, thus leading to more effective therapies.”

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Targeting Dopaminergic Neurons in ‘Zombie’ State Might Slow Parkinson’s Progression, Study Says

senescence and neurons

Contrary to what is commonly thought, dopamine-producing nerve cells (neurons) that stop functioning in Parkinson’s disease may not die, but instead enter a state of senescence in which they cease to divide and cause damage to healthy neighboring cells, a study found.

In fact, one researcher noted these senescence cells are considered “zombie cells,” a spreading “undead.”  Future therapies that specifically stop senescence may help prevent the disease or slow its progression.

The study, “Loss of SATB1 Induces p21-Dependent Cellular Senescence in Post-mitotic Dopaminergic Neurons,” was published in the journal Cell Stem Cell.

A key hallmark of Parkinson’s disease (PD) is the progressive degeneration of dopaminergic neurons in the brain, resulting in its characteristic motor symptoms.

During the natural process of aging, the main risk factor for both the sporadic and genetic forms of PD, humans and other organisms accumulate senescent cells within their tissues. Cellular senescence refers to when cells cease to divide and grow, and can no longer regenerate tissues.

While cellular senescence is important in both embryonic development and wound healing, and plays a role in preventing the development of certain cancers (by arresting uncontrolled cell growth), it can become detrimental.

Senescent cells tend to emit chemicals into their environment that can damage surrounding cells. In addition to accumulating in healthy, older tissue, senescent cells can abnormally accumulate in disease states.

In fact, recent studies have reported increased markers of cellular senescence in the brains of Parkinson’s patients.

Special AT-rich sequence-binding protein 1 (SATB1) was recently identified as a risk factor for PD. Previous studies have shown that SATB1’s activity is reduced in the most affected brain regions of patients.

Researchers set out to investigate SATB1’s role in dopamine-producing neurons, whose activity is lower than usual in Parkinson’s disease.

The team differentiated human stem cells into dopaminergic neurons in a lab dish; in some of these neurons, they silenced the gene responsible for producing the SATB1 protein.

Genetic deletion of SATB1 induced senescence in dopaminergic nerve cells. In particular, researchers found that a lack of SATB1 led to the characteristic hallmarks of cellular senescence, such as increased oxidative protein damage, damaged mitochondria — a cell’s “powerhouse” or energy source — and enlarged nuclei.

Dopaminergic neurons lacking SATB1 also released certain molecules that caused inflammation and senescence in surrounding neurons.

Further analysis found that in healthy dopaminergic neurons, SATB1 directly binds to the regulatory region of the p21 gene and represses its expression. This gene produces a protein known to promote senescence. As such, in a healthy scenario, SATB1 prevents dopaminergic neurons from entering senescence.

Eliminating SATB1 from another type of neuron, called CTX neurons, did not induce senescence or affected p21 expression.

The researchers believe that “SATB1-dependent repression of [p21] transcription seems to be crucial for [dopaminergic] neuron function.”

These findings may explain why Parkinson’s patients experience a drop in dopamine levels before dopamine neurons actually die.

“They [dopaminergic neurons] loose the function of a neuron even though they are still there,” Markus Riessland, the study’s lead author, said in a press release. “People call these senescent cells zombie cells because they’re undead, basically, and because their dead-like appearance is spreading.”

Reducing the activity of SATB1 in dopaminergic neurons in mice also resulted in the same signs of senescence and high levels of p21 and a local immune reponse.

These senescent neurons “stop the cell cycle and they start secreting inflammatory factors that signal to the immune system, ‘Come here and eat me,’” Riessland explained. “This might really be a novel explanation for why you see certain markers of inflammation in Parkinson’s Disease.”

Importantly, researchers found that p21 is actively expressed in dopaminergic neurons of Parkinson’s patients with the sporadic form of the disease, making these cells more prone to enter into a state of senescence.

The team believes that SATB1 could be a promising target for novel therapies that target senescent cells, called senolytics, which have already been able to improve age-related manifestations in mice.

Importantly, therapeutic strategies that target SATB1 or p21 in Parkinson’s disease could be a “beneficial route to intervention.”

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Can You Be a Rainmaker and Bring Hope to Dry Places?

rainmaker

You may have encountered the term “rainmaker” used in the nonliteral sense. Lindsay McPhail, editorial director of The Wild Woman Magazine, describes a rainmaker as “someone who brings hope to dry and barren places. Someone brave enough to get face to face with her own darkness and vulnerable enough to tell her story.” 

Sharing our stories might be the most healing thing that we can do for someone else. As the saying goes, “Misery loves company.” It’s true. But misery wants company that will help in a constructive, health-giving way. 

If we sit down to start sharing our woes with someone who desperately needs hope, we might make their problems worse. But if we tell our story in a way that encourages the other person, and makes them feel understood, supported, and watered in their barren places while shedding light on their darkness, we might help them to stand on their own two feet and move forward feeling restored.

But how do you encourage others with Parkinson’s disease when you need reassurance yourself? How can you feel understood in your experience of this disease when no one seems to be listening? 

When you need light, you may believe that the darkness will never dissipate. When you crave water, you feel as if you’ll never escape the dry, barren desert. Hope can seem unobtainable.

But hope exists, even if it seems remote. It comes in the guise of courage that refuses to quit. You show up to exercise, and hope appears in the form of perseverance and endurance. Hope shines through as determination and strength of character. It pushes forward even when you feel pulled back. It takes one day, one hour, one minute at a time, because you know that — deep down inside — hope exists, or you would have thrown in the towel long ago.

Hope enables you to stand on your own two feet. As a rainmaker, you share your story to help another person out of their darkness and into the light. You have shared hope and, thus, the gift of life.

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Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.

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Review Addresses Problems in Studies of the Gut Microbiome in Parkinson’s

gut microbiome study, Parkinson's

Studies on gut bacteria in Parkinson’s disease differ in their findings and important methodological details, according to a new review that highlights these differences and proposes strategies to mitigate them in the future.

The study, titled “Increasing Comparability and Utility of Gut Microbiome Studies in Parkinson’s Disease: A Systematic Review,” was published in the Journal of Parkinson’s Disease.

Although Parkinson’s is often thought of as a disorder of the brain, the gut likely plays an important role in the disease, but it has only been seriously studied in recent years. A number of studies have recently focused on how the gut microbiome — the bacteria that live inside the intestines — might impact Parkinson’s.

“As more studies investigate the gut microbiome composition in [Parkinson’s], it is important to compare the findings of these studies to get an overview of the changes present in the disease,” Jeffrey M. Boertien, MSc, a PhD candidate at the University of Groningen and co-author of the new review, said in a press release. “It is even more important to compare the methods used in the various studies. Especially as the studies report different and sometimes even contradictory results.”

The review focused on 16 studies published in the past five years. These studies included populations ranging from 10 to 197 people with Parkinson’s and 10 to 130 people without the disease. Notably, even at the level of selecting individuals to include, several studies run into methodological problems; many had large differences in age and sex distribution between the two groups, and “age and sex are well-known determinants of gut microbiome composition,” the review authors wrote.

The authors speculated that one reason for the differences may be the inclusion of spouses or other people living with Parkinson’s patients for use as controls. On one level, this may help account for environmental factors, which can influence the gut microbiome, but the authors stressed that “differences in age and sex distribution should be accounted for as potential confounders in all case-control gut microbiome studies.”

Major differences were also found between studies in how the gut bacteria were assessed — from what taxonomic levels were investigated (phylum, genus, etc.), to how samples were collected, to what bioinformatics techniques were used to analyze the data. All of these could account, at least in part, for different results found from study to study.

A number of differences between studies were found. While the researchers noted that, “several findings, such as an increase of Verrucomicrobiaceae and Akkermansia, and a decrease of Prevotellaceae were robustly replicated,” other findings were inconsistent or even directly contradictory. For example, some studies reported increased numbers of the bacterial groups Lactobacillaceae and Bacteroidetes in people with Parkinson’s, while others found the opposite.

In addition, the effect of dopaminergic medication on gut microbiome composition has not been studied directly, the authors said.

“Nonetheless, the effect of dopaminergic medication can be hypothesized to be substantial, as effects of various medications on gut microbiota composition have been described,” they wrote.

“There is currently no consensus on [Parkinson’s]-specific changes in microbiome composition and their pathophysiological implications due to inconsistent results, differences in methodologies and unaddressed confounders,” said review co-author Filip Scheperjans, MD, PhD, of Helsinki University Hospital.

As to strategies to help address this problem, some — such as more careful selection of study participants — are self-evident. More broadly, the authors suggested that greater transparency and sharing data, particularly raw data, could make it easier to draw broad conclusions: “public availability of raw sequencing data and sample metadata would allow for an integrative dataset of [Parkinson’s] microbiome studies that could address various possible confounders.”

“If we combine all data, it will be easier to distinguish changes that are associated with [Parkinson’s] from noise,” said Scheperjans. “However, further research is still required to increase our understanding of the possible role of gut microbiota in [Parkinson’s]. It is important to emphasize that no microbiota-based treatment for [Parkinson’s] exists to date. We advise [Parkinson’s] patients not to start self-treatment with probiotics or undergo fecal microbiota transplantation without consulting with their doctors in order to avoid potential harm.”

Still, exploiting the gut microbiome may be a potential strategy for the clinical management of the disease in the future, the researchers said.

“Specific changes might serve as a biomarker with which we can recognize [Parkinson’s] or specific subtypes of [Parkinsons’]. Since gut complaints can occur very early in the disease process, this might help to identify patients in the early stages of the disease, possibly even before the appearance of motor symptoms such as tremor and rigidity,” said Boertien. “If gut microbiota play an important role in the disease process, this might lead to new treatment options for [Parkinson’s].”

Several of the review authors disclosed potential conflicts of interest, such as owning patents related to the gut microbiome and Parkinson’s disease.

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Earlier Onset, Cognitive Impairment and Higher Medication Use Linked to Increased Parkinson’s-related Mortality

Parkinson's mortality studied

Earlier onset of disease, early impairment of memory and thinking, and higher daily use of antiparkinson medication, are associated with increased risk of death related to Parkinson’s disease (PD), according to a study that followed newly diagnosed patients for more than 10 years.

Conversely, being male, the severity of disease symptoms, and general cognitive ability do not seem to contribute significantly to Parkinson’s-related mortality.

The study, “Overall and Disease Related Mortality in Parkinson’s Disease – a Longitudinal Cohort Study,” was published in the Journal of Parkinson’s Disease.

Research has shown that Parkinson’s disease is associated with increased mortality when compared to the general population. However, it remains unclear which factors contribute to this increased mortality and which could be used to predict patients who are at greater risk.

“The reduced life span of patients with PD has been reported earlier, but research on factors associated with this decline has been scarce and of limited scope. While life expectancy is a crude outcome, it is clearly a relevant one, and its association with PD-specific characteristics might help to further understand the heterogeneity of disease often reported in PD,” said Rob M.A. de Bie, MD, PhD, in a press release . De Bie is the study’s senior leader and a neurologist at the University of Amsterdam, Netherlands.

To evaluate potential risk factors for overall and Parkinson’s-related mortality, de Bie and colleagues collected detailed information from a group of 129 newly diagnosed Parkinson’s patients (median age 68.2 years) for at least 13 years, or until death.

This study differed from previous studies because it focused on identifying factors that influenced patients’ mortality related to the disease itself and not just overall mortality.

The median survival of patients after diagnosis was 11.8 years and 85 patients died during the study. The majority of patients were already on levodopa, one of the main medications used to treat the symptoms of Parkinson’s, when they entered the study.

Looking at patients’ characteristics and their survival over time, researchers found that earlier onset of disease, mild cognitive impairment (memory and thinking), and higher daily antiparkinson medication use (measured in levodopa equivalent dose) were all associated with increased death rates related to Parkinson’s.

On the contrary, factors such as male sex, motor symptom severity (as measured by the UPDRS scale), and general cognitive ability (assessed using the Mini-Mental State Examination) did not contribute significantly to the findings.

Higher overall mortality, related or not to Parkinson’s disease, was associated with older age, male sex, greater daily use of antiparkinsonian medications, and mild cognitive impairment.

Despite this study pointing out factors associated with Parkinson’s-related mortality, researchers stressed that due to the observational nature of this data (patients were only followed, with no intervention) it cannot be used to infer cause-effect relationships.

“Therefore, our results do not imply any harm of levodopa treatment,” the researchers wrote. “Theoretically, the most plausible explanation is that progressive disease in terms of motor impairment leads to both early levodopa treatment and increased mortality.”

The team also recommended caution when applying results from population studies such as theirs to individual patients.

“While we found life expectancy in PD to be decreased on average, accurate prediction of individual life expectancy is a more difficult endeavor. Nonetheless, individualized care starts with a better understanding of differences between patients, and our findings show that individual differences in the manifestation of PD are associated with life expectancy,” noted the study’s lead author Jeroen Hoogland, also from the University of Amsterdam.

To provide more accurate predictions of mortality, future research could combine individual patient data with imaging and biomarker-related measures, accompanied by more detailed follow-ups, the team suggested.

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Oral Magnesium Compound Able to Reach Brain Seen to Slow Motor Decline, Neuronal Loss in Early Study

magnesium and motor skills

A specific form of magnesium taken orally and able to readily enter the brain was seen to ease Parkinson’s-related motor problems and nerve cell loss in a mouse model of the disorder.

The study, “Treatment Of Magnesium-L-Threonate Elevates The Magnesium Level In The Cerebrospinal Fluid And Attenuates Motor Deficits And Dopamine Neuron Loss In A Mouse Model Of Parkinson’s disease,” was published in Neuropsychiatric Disease and Treatment.

Magnesium is a mineral important to several body functions, including nerve cell transmission and neuromuscular coordination. Low levels of this mineral have been reported in motor regions of the brains of Parkinson’s patients. Population studies of the disease (epidemiological studies) also report a higher incidence of the neurodegenerative disorder in the presence of magnesium deficiency.

Therefore, in theory, raising brain magnesium levels could ease Parkinson’s manifestations.

Magnesium sulfate is the first choice as a clinical magnesium supplement, but systemic administration of magnesium sulfate fails to increase magnesium levels in the cerebrospinal fluid (CSF), the liquid that flows in and around the brain and spinal cord.

Using a mouse model of Parkinson’s, researchers investigated the protective effect of magnesium-L-threonate, a magnesium compound that is very permeable and can penetrate the blood-brain barrier — a semipermeable membrane that protects the brain from the outside environment — to reach the brain.

For a month, animals were given one of three doses of magnesium-L-threonate (0.8, 1.2, and 1.6 mM) or magnesium sulfate in their drinking water. Then, on the third week of the magnesium regimen, and for 7 seven consecutive days, these mice received MPTP, a neurotoxin that induces death of dopamine-producing neurons and mimics Parkinson’s symptoms.

Scientists analyzed the animals’ motor behavior and the amount of nerve cell loss within the substantia nigra and the striatum, both motor control brain areas primarily affected by Parkinson’s.

Magnesium levels in blood serum and the cerebrospinal fluid were measured after either form of oral magnesium in healthy mice.

Magnesium concentrations in both the CSF and serum rose with magnesium-L-threonate use, while magnesium sulfate only increased blood magnesium levels and did not affect CSF levels.

Diseased mice with Parkinson’s-like symptoms given magnesium-L-threonate for four weeks were seen to have lesser motor decline and better motor coordination compared to untreated diseased mice. Treatment also slowed dopaminergic neuronal loss in a dose-dependent manner, with the 1.2 mM dose showing the greatest neuroprotective potential.

Additionally, magnesium-L-threonate treatment inhibited what’s called inducible nitric oxide synthase (iNOS)-mediated inflammation and oxidative stress. (Oxidative stress refers to cellular damage as a consequence of high levels of oxidant molecules and is associated with a number of diseases, including Parkinson’s.)

Treatment with magnesium sulfate had a marginal effect on the animals’ motor behavior, but no effect on neurodegeneration.

“[O]ur results indicate MgT [magnesium-L-threonate] can significantly attenuate MPTP-induced motor deficits and DA [dopaminergic] neuron injury, which may be related to its ability of increasing the Mg [magnesium] concentration in the CSF [cerebrospinal fluid],” the researchers wrote.

“These data also suggest that … only supplementation of [magnesium] in the periphery does not help to protect the brain and the combination of [magnesium] with an agent that promotes its transportation to the brain is essential for the neuroprotection of this element,” they added.

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2 Distinct Types of Parkinson’s May Exist Based on Nervous System Origin of Disease, Study Suggests

nervous system

Parkinson’s disease may be classified by into two distinct subtypes based on where in the nervous system the disease starts, a study proposes. Its findings could have major implications for the development of new treatments.

The paper, “Brain-First versus Gut-First Parkinson’s Disease: A Hypothesis,” was published in the Journal of Parkinson’s Disease.

The nervous system can be divided, broadly, into two parts: the central nervous system (CNS), which contains the brain and spinal cord, and the peripheral nervous system (PNS), which covers everything else.

Although Parkinson’s disease (PD) is generally thought of as a disorder of the brain, a paper published in 2003 suggested it actually starts in the PNS — specifically, in the nerves in and around the gut and the nose — and then spreads to the brain.

Researchers here reviewed a plethora of available evidence — including data from humans and from animal models — and proposed that this PNS-first model may indeed be correct, but only some of the time. In other cases, Parkinson’s might actually start in the CNS.

“The discussion about the origins of PD is often framed as an ‘either-or’, i.e., either all PD cases start in the gut or all cases start in the brain. However, much of the evidence seems compatible with both these interpretations. Thus, we need to entertain the possibility that both scenarios are actually true,” Nathalie Van Den Berge, MSc, PhD, a postdoc at Aarhus University in Denmark and a study co-author, said in a press release.

While some post-mortem studies of brain tissue from Parkinson’s patients suggest the disease starts in PNS of the gut and nose before spreading “via the nerves into the brain,” others do not agree.

“In some cases, the brains do not contain pathology at the important ‘entry points’ into the brain, such as the dorsal vagus nucleus at the bottom of the brainstem. The gut-first versus brain-first hypothesis posited in this review provides a scenario that can reconcile these discrepant findings … into one single coherent theory about the origins of PD,” Per Borghammer, MD, PhD, DMSc, also a study author and Aarhus professor, added.

The researchers particularly focused on one Parkinson’s symptom, REM [rapid eye movement] sleep behavior disorder (RBD), characterized by uncontrolled and violent arm and leg movements, and acting out dreams during sleep.

This often occurs in the early stages of PD, but not always. The researchers suggested that this may be because RBD is associated with Parkinson’s that originates in the PNS, but not with the disease that originates in the CNS.

Supporting this idea, they noted that previous imaging studies of Parkinson’s patients showed those with RBD had more evident PNS damage than those without RBD or whose RBD status was unknown. In contrast, in many people with RBD, the dopamine pathways in the brain that become dysregulated in PD appear within normal limits in the earliest stages.

“Put together, it appears that [alpha-synuclein] pathology in the PNS is more frequent in RBD-positive PD compared to RBD-negative cases,” the researchers wrote.

Regarding familial forms of Parkinson’s disease (those caused by specific mutations), the researchers believe that some mutations are mainly associated with a CNS-first hypothesis, such as those in the PARKIN, PARK7 or PINK1 genes, while others, such as those in the GBA and SNCA genes, are associated with a PNS-first hypothesis.

This hypothesis could have major implications for Parkinson’s studies and treatment.

“If the brain-first vs body-first hypothesis is correct, we need to intensify the research into understanding risk factors and triggering factors for these two subtypes,” Van Den Berge said.

Treatment could be tailored to a patient’s subtype, Borghammer added.

“It is probable that these different types of PD need different treatment strategies. It may be possible to prevent the ‘gut-first’ type of PD through interventions targeting the gut, such as probiotics, fecal transplants, and anti-inflammatory treatments,” Borghammer said. “However, these strategies might not work with respect to treating and preventing the brain-first type. Thus, a personalized treatment strategy will be required, and we need to be able to identify these subtypes of PD in the individual patient.”

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