A New Look at Freezing: ‘Scenario Looping Breakdowns’ As an Early Symptom

Reframing how we describe symptoms of Parkinson’s disease (PD) can help us understand the disease spectrum concept that I introduced last week. One such symptom is the movement disorder called “freezing.” I believe there is an early PD symptom variation of freezing, called “scenario looping breakdown.” Understanding it may help people realize what drives this symptom.
When I first heard the term freezing, I pictured a deer frozen in the headlights of a car. It wasn’t until I started experiencing subtle variations of inability to move a given muscle (it was frozen) that I understood freezing connected to something I lectured on when I worked with people who had neurological impairments. At that time, I called it, “scenario looping.”
Scenario looping is best described with a story: Imagine you’re at the grocery store to pick up dinner supplies. It’s early afternoon (no pressure) and while strolling aisles, your eyes wander about, checking people out. You see somebody vaguely familiar. The person turns to face you and your heart skips. It’s that gorgeous person you have a passionate crush on, walking to you with a big smile. Your face as red as the beets in the produce section, you smile and engage in pleasantries. The conversation turns to, “Well, what are you doing after you’re done shopping?” Every fiber in your body screams at you, “I want to spend intimate time with this person right now!” At the same time, you have in your hand a small shopping basket with spaghetti sauce, specialty meatballs, and gluten-free noodles. What do you do?
Arriving at the answer involves “looping” through the scenario over and over, weighing the consequences of any action until you arrive at a satisfactory answer of what to do. Scenarios of all types are presented to us every day. We constantly face decisions about how to use our time, how to structure our language, and even how to structure our internal dialogue. All of this connects to scenario looping.
Scenario looping also connects to motor sequencing. If you wanted to leave the spaghetti behind and immediately walk out with your old flame, then you would need to tell your body to do the necessary motor sequences. We may not think of motor sequences as part of how we interact with the day because so much of our movement, like walking, is nearly automatic.
The term “freezing” associated with PD commonly refers to freezing while walking. Walking is often automatic. We have done so much walking in our lives that it has become a motor sequence we don’t think of — an overlearned motor scenario loop. We don’t have to think about every step we take. We can run on autopilot. Think of autopilot as a small string of actions that almost automatically function in the background of your mind. If autopilot functions properly, you can simultaneously walk and have a conversation or listen to music. As the saying goes, “You can walk and chew gum at the same time.”
It is possible that scenario looping breakdowns are symptoms indicating PD’s

Source: Parkinson's News Today

Eradication of Helicobacter pylori Infections Could Ease Gut Symptoms, Motor Dysfunction in Parkinson’s Patients, Study Suggests

Eradicating Helicobacter pylori infections could improve motor function, ease gut symptoms and increase levodopa’s effectiveness in Parkinson’s patients, according to a review study.
The research, “Stomaching the Possibility of a Pathogenic Role for Helicobacter pylori in Parkinson’s Disease,” was published in the Journal of Parkinson’s Disease.
While a small subset of Parkinson’s cases have genetic causes, most cases are sporadic, with unknown environmental causes. Gastrointestinal symptoms such as constipation precede motor complications, suggesting that the disease might start in the gut and subsequently spread to the brain along the brain-gut axis.
This has been observed in rats, where injection of alpha-synuclein fibrils — the major component of Parkinson’s characteristic Lewy bodies — into the gut induced Parkinson’s-related pathology.
Chronic infections with H. pylori affect half the world’s population and may cause gastritis, ulcers, and stomach cancer, as well as various gastrointestinal symptoms. A greater occurrence of ulcers in patients with Parkinson’s was first reported in 1961. More recently, a link between H. pylori and Parkinson’s has been shown, with consistent reports of higher risk for Parkinson’s in people infected with this type of bacteria.
The research team reviewed all major studies that discussed the possible link between H. pylori and Parkinson’s, which led to four key findings:

Having Parkinson’s increases by 1.5 to 3 times the risk of H. pylori infection.
H. pylori infection worsens motor function in Parkinson’s patients.
Eradication of H. pylori with triple therapy improved motor function in Parkinson’s patients compared to infected patients in clinical studies.
Eradication of H. pylori improved gut absorption and increased plasma levels of Parkinson’s gold-standard treatment levodopa in patients. Research had shown that H. pylori binds to levodopa, preventing it from reaching the brain and reducing its effectiveness

As for pathways linking this bacterial infection with Parkinson’s, the researchers provided three possible explanations besides impaired levodopa effectiveness. One explanation is that bacterial toxins produced by H. pylori or alterations to the body’s own molecules such as cholesterol can damage neurons.
The infection can also cause a massive inflammatory response in the stomach, which would become systemic, cross the blood-brain barrier (BBB) — a semipermeable barrier that protects the brain — and worsen Parkinson’s symptoms and pathology. H. pylori could also reach the brain by colonizing immune cells that cross the BBB themselves.
Finally, H. pylori may disrupt the normal gut microbial population, or microbiota, altering inflammatory mediators that predispose a person to Parkinson’s disease.
“Our conclusion is that there is a strong enough link between the H. pylori and Parkinson’s disease that additional studies are warranted to determine the possible causal relationship,” David J. McGee, PhD, the study’s lead author and a professor at the Department of Microbiology and Immunology, LSU Health Sciences Center-Shreveport, said in a press release.
Although current evidence suggests that “eradication of H. pylori or return of the gut microflora to the proper balance in [Parkinson’s] patients may ameliorate gut symptoms, L-dopa malabsorption, and motor dysfunction,” scientists still have little information on whether H. pylori infection “is a predisposing factor, disease progression modifier, or even a direct cause of [Parkinson’s]”, the authors wrote.
Specifically, future studies should explore the interactions of H. pylori with neurons and levodopa, the role of H. pylori toxins, how inflammatory responses to H. pylori may

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Nuplazid’s Mortality Risk Not Different from Seroquel, Combo Treatment, Study Finds

Treatment with Nuplazid (pimavanserin) does not lead to a different mortality risk compared to the antipsychotic medication Seroquel (quetiapine), or to combination treatment with both medications, in patients with Parkinson’s psychosis, according to results from a large study.
The study, “Mortality in patients with Parkinson disease psychosis receiving pimavanserin and quetiapine” was published in the journal Neurology.
In April 2016, Acadia Pharmaceuticals’ Nuplazid became the first therapy approved by the U.S. Food and Drug Administration (FDA) for hallucinations and delusions associated with Parkinson’s psychosis.
However, two years later, a CNN report cited an analysis by the nonprofit Institute for Safe Medication Practices, which found a total of 700 deaths in the FDA’s Adverse Event Reporting System — including 500 among Parkinson’s patients in which Nuplazid was the only therapy likely involved — in the nine months following Nuplazid’s arrival on the market in June 2016.
Now, researchers at University of California San Diego School of Medicine explored the medication’s safety further. “We wanted to better understand and assess the risks of using pimavanserin (Nuplazid) within our own patient community, either alone or in combination with other commonly prescribed medications,” Fatta B. Nahab, MD, the study’s senior author, said in a press release.
Besides Nuplazid, the team focused on Seroquel, a second-generation antipsychotic (SGA), which is often used to treat Parkinson’s psychosis. Results were mixed. Use of Seroquel and other SGAs led to concerns about increased morbidity and mortality in patients with dementia or those with Parkinson’s, prompting an FDA black box warning.
Unlike Seroquel, Nuplazid does not affect dopamine receptors, so it does not interfere with the effectiveness of Parkinson’s treatments for motor symptoms.
The team conducted a retrospective analysis of 4,478 UC San Diego Health patients with Parkinson’s, of whom 676 were being prescribed Nuplazid, Seroquel, or both, between April 29, 2016 and April 29, 2018.
Results showed that patients treated with Nuplazid alone (113 patients, mean age 75.9 years) had a lower mortality percentage when compared to those treated with quetiapine only (505 patients, mean age 75.2 years), or with both compounds (58 patients, mean age 74.1 years ). However, the differences were not statistically significant.
When compared to 784 Parkinson’s patients not on these medications (mean age 80 years), the results revealed a significantly greater risk (74%) of mortality in the Seroquel-only group and a trend toward increased risk in the combination treatment group.
“It’s reasonable to assume, however, that individuals requiring these medications have greater disease severity and are at a higher risk of complications and death,” Nahab noted.
A subset of the patients receiving both medications exhibited the highest rate of mortality, although not statistically different. Importantly, the team noted that the combination therapy’s safety is not yet established, as the pivotal Phase 3 trial of Nuplazid (NCT01174004) excluded individuals on antipsychotics.
“Our findings provide the largest comparative report of mortality risk in [Parkinson’s psychosis],” researchers wrote.
However, Nahab noted limitations on the study’s design and nature, which precluded the determination of cause of death or duration of antipsychotic treatment.
“While the results pertaining to [Nuplazid] provide some reassurance for clinicians, patients, and families, future studies

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Parkinson’s Foundation Adds 3 Centers of Excellence to Its Network

Ohio’s Cleveland Clinic will officially become a Parkinson’s Foundation Center of Excellence on Oct. 2, followed by the Medical University of South Carolina in Charleston on Oct. 4, and the Cleveland Clinic Nevada in Las Vegas on Oct. 19.
Next month’s three plaque unveiling ceremonies will bring the number of U.S. and overseas facilities bearing the designation to 48, said John Lehr, CEO of the Parkinson’s Foundation.
“The centers are already functional, and up and running,” Lehr told Parkinson’s News Today in a Sept. 26 phone interview. “What this designation means is that they have achieved a certain level of excellence as defined by the foundation. There’s a series of criteria we look at. All these facilities competed with 28 other potential centers, and after a careful yearlong review, we determined that these three were the best qualified to become centers of excellence.”
In other words, Lehr said, these three centers — along with the other 45 that have already received the designation — are “fully credentialed in terms of having movement disorder specialists and neurologists trained in Parkinson’s-specific issues.”
Such centers are staffed with teams of professionals in physical therapy, occupational therapy, social work, and mental health.
“They’re already providing patients with the full range of ancillary services and also conducting research,” said Lehr, estimating they serve a combined 120,000 Parkinson’s patients annually.
Parkinson’s Foundation CEO John Lehr
Among patient advocacy groups, the Centers of Excellence concept originated with the Cystic Fibrosis Foundation (CFF), where Lehr worked from 2004-2009 on the business side. Among other things at CFF, he ran a national campaign that raised $175 million — money that paid for the early-phase trials of the Vertex therapies that ultimately became Kalydeco (ivacaftor) and Orkambi (ivacaftor/lumacaftor).
“This is the same concept,” Lehr said. “In each disease-specific area where you have these types of centers, it’s a signal to patients with that disease — and their caregivers — that they can be assured they’re getting the highest level of care.”
The expansion of the Centers of Excellence project, first announced earlier this month, is funded through donations from individuals. The largest single gift — in the amount of $450,000 — comes from philanthropist Stephen Bittel, founder and CEO of the South Florida real-estate developer Terranova.
Last year, the nonprofit foundation — which has offices in New York and Miami — raised about $32 million in donations and channeled that money into three main areas: improving outcomes through better clinical care; funding basic clinical and epidemiological research to understand the causes and consequences of Parkinson’s; and investing in educational resources for people with and affected by Parkinson’s.
Of the foundation’s 45 currently designated Centers of Excellence, 32 are in the United States. The remaining 13 are scattered throughout the world, including Australia, Canada, Germany, Great Britain, Israel, the Netherlands, Singapore, Taiwan, and the United Arab Emirates.
A study funded by the Parkinson’s Foundation and published in July predicted that 930,000 Americans would be living with the disease by 2020, rising to more than 1.2 million by 2030. According to the “Parkinson’s Prevalence Project” report — published in the journal Nature — the estimated

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Grape Skin Extract Has Beneficial Effect on Mitochondria in Flies With Parkinson’s

Grape skin extract improves muscle function and extends the lifespan of flies with Parkinson’s disease, a study shows.
The neuroprotective effect of grape skin extract was due to its potential to rescue mitochondria — cells’ powerhouses — from defects caused by the disease.
The study, “Skin extract improves muscle function and extends lifespan of a Drosophila model of Parkinson’s disease through activation of mitophagy,” was published in the journal Experimental Gerontology.
The health benefits of drinking red wine have been widely reported, and evidence is accumulating to suggest that wine consumption has potential value against age-related neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease.
The antioxidant and anti-inflammatory activities of red wine polyphenols, such as resveratrol, have been pointed to as the main reasons for its beneficial effects. But studies also have revealed that resveratrol could prevent the formation of toxic amyloid aggregates that often characterize neurodegenerative diseases.
Besides polyphenols, grape skin and seeds also contain anti-oxidative components, including proanthocyanidine and quarcetin, which may actively contribute to protecting against oxidative stress and mediated tissue injury.
Oxidative stress is an imbalance between the production of free radicals and the ability of cells to detoxify them. These free radicals, or reactive oxygen species, are harmful to the cells and are associated with a number of diseases, including Parkinson’s disease.
Researchers at Stanford University School of Medicine evaluated the effect of dietary supplementation with grape skin extract left from red wine-production in a fly model of Parkinson’s disease.
The flies were genetically engineered to have a mutated version of the PINK1 gene, which is known to be linked to the human disease.
Loss of function of the PINK1 gene led to a significant reduction in flies’ lifespan, from a median time of roughly 18 days down to 11 days. Diet supplementation with 8% grape skin extract improved flies’ survival time to a median of 15 days. A similar improvement was achieved with a high dose of resveratrol.
Further assessments revealed that PINK1 mutated flies had abnormal wing posture, a feature that was partially reversed with 8% and 16% grape skin extract, as well as with a high dose of resveratrol.
These results suggest that grape skin extract have potential to improve survival and prevent indirect flight muscle degeneration, and its beneficial effect is mediated by components other than resveratrol alone.
The researchers found that both treatment with grape skin extract and resveratrol could significantly reduce — by about half — the amount of damaging oxygen reactive elements. In addition, it also could prevent the aggregation of mitochondria in muscle and in dopamine-producing nerve cells, protecting them from dying.
After further experiments the team confirmed that the beneficial impact of grape skin extract was sustained by its protective effect on mitochondria activity, and re-activation of the destruction process of damaged mitochondria.
Collectively, these results suggest that “manipulation of the mitochondrial pathways,” with pharmacological agents or alternative strategies such as grape skin extract, “may prove beneficial to combat Parkinson’s disease,” researchers wrote.
“The various components in grape skin extract may act together in a multi-pronged manner” targeting several damaging mechanisms involved in

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The ABCs of Parkinson’s: ‘G’ Is for Girls, Gaits, and Gifts

A continuation of the “ABCs of Parkinson’s” series.
The girls
OK, OK. So I’m reaching for examples of the letter “G” to fit for this section. Girls? Yes, girls, speaking toward the female sex. And there is evidence that between boys and girls — er, men and women — that the men outnumber the women when it comes to Parkinson’s disease.
According to ParkinsonsDisease.net, “Parkinson’s disease (PD) is found more frequently in men than in women, occurring in men 50% more than in women.” Is there a reason, an explanation, for this? According to the same article, researchers haven’t yet discovered the answer to that question but suggest that “the protective effect of estrogen in women” may have a role to play. Researchers also tend to attribute head trauma (such as that found in football players, boxers, etc.), which is higher in men than women, as part of the reason for Parkinson’s.
The gait
While there may be differences between men and women when it comes to having Parkinson’s disease, there are also similarities in the symptoms they share with the disease. This includes issues with gait. Because it is one of the symptoms of Parkinson’s that can be seen, it tends to draw undesired attention. 
There is a freezing of one’s gait, which is basically just that: the inability to walk in a smooth, fluid motion without stopping. The patient “freezes up” and has difficulty moving or stepping forward.
Patients also have what is known as a shuffling gait, noted by the appearance of the patient dragging their feet and appearing to fall forward when they walk. These symptoms (a freezing or shuffling gait) usually develop over time during the disease’s progression.
The gifts
Many people with Parkinson’s disease have made reference to having been given a “gift,” so to speak. They feel that priorities shifted after finding out they had Parkinson’s disease. What once was important was no longer, and what is now important, once never was. Family and friendships became foremost. The ability to see what was truly important in life became clearer. Taking things for granted became obsolete and being thankful took on new life. New friendships have formed through having Parkinson’s or being a caregiver of a person with PD.
Gifts don’t have to be wrapped with bows and wrapping paper. Some of the best gifts can’t be wrapped at all, or they come wrapped in flesh. We may have to struggle with other aspects of Parkinson’s disease, but when it comes down to deciding whether PD can be considered a gift or not, it all depends on the recipient.
***
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

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Lack of Exercise Increases Parkinson’s Risk in Men, Review Study Confirms

Men who lack physical activity have a higher risk of developing Parkinson’s disease at some point in their lives, a systematic review has found. Importantly, findings revealed that even moderate exercise can be enough to counteract this effect.
The review, “Association of Levels of Physical Activity With Risk of Parkinson Disease,” was published in JAMA Network Open.
Parkinson’s disease, the second most prevalent neurodegenerative disease of the elderly (after Alzheimer’s disease), is characterized by the gradual loss of muscle control, sometimes accompanied by cognitive deficits.
The underlying causes of Parkinson’s disease are still poorly understood by scientists, but likely involve a combination of genetic and environmental risk factors. In the past 20 years, several prospective studies have focused on the effect of lifestyle factors, such as exercise, on Parkinson’s.
Although physical activity is known to decrease the risk of developing several conditions, including cardiovascular disease, stroke and diabetes, systematic studies addressing the impact of physical activity on Parkinson’s risk are few in number and often inconsistent regarding their methodology and data interpretation.
This systematic review focused on gathering data from previously published prospective studies to quantify the dose-response association between physical activity and Parkinson’s risk.
Following an initial period of literature research performed by two independent investigators, a total of eight prospective studies involving 544,336 participants — including 2,192 Parkinson’s patients with a median follow-up period of 12 years — focused on the relationship between physical activity and Parkinson’s risk, were included in the review.
Pooled data from all the studies showed that participants included in the highest category of total physical activity had a 29% lower risk of developing Parkinson’s compared to those who did not engage in any moderate-to-vigorous physical activity. Conversely, light physical activity was not linked to Parkinson’s risk.
Further subgroup analyses revealed that the relationship between physical activity and Parkinson’s risk was not influenced by geographic region, follow-up duration, population size, or study quality. They were  affected, however, by gender, as the link between exercise and Parkinson’s risk was more robust among men, regardless of physical activity levels, compared to women.
Finally, the dose-response analysis showed that for each increase of 10 metabolic equivalents of task (MET) — a method to measure the energy cost of physical activities — of hours per week in total or moderate-to-vigorous physical activity, Parkinson’srisk in men decreased by 10% and 17%, respectively. This dose-response effect was not observed among women.
“[O]ur pooled analysis of more than half a million adults revealed that higher levels of physical activity —particularly moderate to vigorous activity — are associated with a lower risk of developing PD [Parkinson’s disease]. These benefits were significant among men, but were less robust among women,” researchers wrote.
“These findings may help guide physicians and health care policy makers in making recommendations and developing guidelines with respect to the degree of physical activity that can help reduce the risk of PD at both the individual level and the population level. More epidemiological studies with large sample size and detailed quantification of physical activity will help establish more precise information regarding this association,” they concluded.
The post Lack of

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IRAK4 Protein Inhibitor Could Lead to Treatment for Parkinson’s, Other Neuroinflammatory Diseases

A newly discovered inhibitor of the immune protein IRAK4, known as the “master switch” in the development of several diseases, could lead to treatments for autoimmune diseases and neuroinflammatory disorders such as Parkinson’s, according to developer Noxopharm and its majority-owned subsidiary Nyrada.
Pre-clinical studies are ongoing to find the most appropriate therapeutic indications for this discovery. Clinical studies are expected in 2020.
Recent evidence has shown that IRAK4 is a crucial regulator in the body’s innate immune response — the body’s first line of defense — against foreign pathogens and leads to the production of pro-inflammatory molecules called cytokines.
As its abnormal function in innate immune cells is implicated in the development of chronic inflammatory and autoimmune diseases, IRAK4 inhibitors have been regarded as the next generation of anti-inflammatory treatments for autoimmune conditions, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, and lupus.
The new compound leads to potent inhibition of IRAK4 and is able to cross the blood-brain barrier and blood-nerve barriers. According to Australia-based Noxopharm, this suggests the new compound could be used to target neuroinflammatory diseases of the central nervous system — such as Parkinson’s, Alzheimer’s, multiple sclerosis, amyotrophic lateral sclerosis — and the body’s peripheral nerves, in particular diabetic peripheral neuropathy.
The blood brain barrier is a semipermeable membrane that protects the brain against the external environment, and is a major barrier for the efficient delivery of certain therapeutics that need to reach the brain and central nervous system.
“We see our discovery as a breakthrough in providing the tools needed to address inflammatory and autoimmune diseases of the nervous system,” James Bonnar, Nyrada’s vice-president, research & development, said in a press release. Bonnar noted that the development of IRAK4 inhibitors is being pursued in rheumatoid arthritis, gouty arthritis and lupus.
“I see this as a major development,” said Graham Kelly, Noxopharm’s CEO. While noting that it helps Noxopharm evolve into a global biotech company, Kelly added that “at the patient level, it represents a realistic prospect for finally being able to provide treatment for a number of insidious diseases affecting the nervous system, which have defied successful management to date.”
Besides Alzheimer’s, Parkinson’s and multiple sclerosis, Kelly said that neuroinflammation is “associated even with psychiatric conditions such as depression, bipolar disorder and schizophrenia.”
“Having a drug that blocks IRAK4 and all its downstream pro-inflammatory cytokine [signaling] effects, combined with its ability to reach the brain in sufficient levels, is an exciting breakthrough that has resulted from a lot of hard work by a team of Australian chemists and scientists,” Kelly added.
U.S. company Nyrada is two-thirds owned by Noxopharm and is responsible for the non-oncology drug development programs, including an anti-inflammatory, a neuroprotectant and a PCSK9 inhibitor compound. Of note, PCSK9 is a protein involved in regulating the amount of cholesterol in the blood.
Noxopharm recently secured a U.S. provisional patent application and a Patent Cooperative Treaty (PCT) patent application.
The post IRAK4 Protein Inhibitor Could Lead to Treatment for Parkinson’s, Other Neuroinflammatory Diseases appeared first on Parkinson’s News Today.

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Non-Motor Symptoms During Wearing-off Periods Associated with Worse Quality of Life in Parkinson’s Patients

Parkinson’s patients with non-motor symptoms during “wearing-off” periods — when symptoms return as their medication wears off — have a significantly worse quality of life compared to patients who only experience the return of motor symptoms, a new study shows.
The study, “Motor and non-motor wearing-off and its impact in the quality of life of patients with Parkinson’s disease,” was published in the journal Arquivos de Neuro-Psiquiatria.
Motor fluctuations refer to the alterations between periods of being “on,” during which a Parkinson’s patient experiences a positive response to medication (generally levodopa), and being “off,” during which the medication wears off and symptoms return.
“Off” periods are more common as the disease progresses and people take medication for a longer period of time.
Motor fluctuations in patients with Parkinson’s disease have been studied extensively. But little is known about non-motor symptoms during “on” and “off” periods.
Motor wearing-off includes the re-emergence of motor symptoms such as tremor, rigidity, and bradykinesia (slowness of movement). Non-motor symptoms include anxiety, fatigue, and depression.
Non-motor symptoms have a significant impact on a patient’s quality of life, as the burden can often be more disabling compared to motor symptoms.
Researchers have developed tools to assess wearing-off in Parkinson’s patients. In particular, the wearing-off questionnaire (WOQ-19) has been used in studies as a screening tool to identify which patients experience the wearing-off phenomena.
The team conducted a cross-sectional study to assess the impact of motor and non-motor wearing-off on daily activities and quality of life in Parkinson’s patients. All patients were evaluated using the movement disorders society unified Parkinson’s disease rating scale (MDS-UPDRS, to follow disease progression), the WOQ-19, and the Parkinson’s disease questionnaire-8 (PDQ-8) to assess quality of life.
Among the 271 patients included, 73.4% had wearing-off. Researchers then classified those patients according to the type: 63.8% had mixed wearing-off (motor and non-motor), 32.7% motor, and 3.5% non-motor.
As expected, the MDS-UPDRS part I total score — which assesses non-motor aspects of daily living — was higher (worse) in the non-motor wearing-off group. Interestingly, there were no differences in MDS-UPDRS part I score between patients in the mixed wearing-off group and those who did not experience wearing off.
“This finding suggests that patients with motor wearing-off may have a lower overall burden of non-motor symptoms, while patients with mixed or no wearing-off have similar burdens,” researchers said. “Conversely, patients with non-motor fluctuations also have a higher burden of non-motor symptoms.”
Parkinson’s patients in the non-motor wearing-off group also had the worst score in the PDQ-8, followed by patients in the mixed wearing-off group. On the other hand, patients with no wearing-off and those with only motor wearing-off had a better quality of life.
“[T]he present study shows that both motor and non-motor fluctuations have an impact on activities of daily living and quality of life. However, the presence of non-motor fluctuations did significantly worsen the quality of life,” the authors wrote.
“The identification and assessment of non-motor fluctuations in the day-to-day clinical practice could result in the improvement of the quality of life of patients with [Parkinson’s disease],” the team concluded.
The post Non-Motor Symptoms During Wearing-off Periods Associated with

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Depression May Aggravate Motor, Cognitive Symptoms in Newly Diagnosed Parkinson’s Patients, Study Reports

Depression in newly diagnosed Parkinson’s patients is associated with initial motor deficits and worse cognitive function, unrelated to dopamine loss, a study suggests.
These patients also require higher doses of medications at follow-up.
The study, “The presence of depression in de novo Parkinson’s disease reflects poor motor compensation,” was published in the journal PLOS ONE.
Early burden of non-motor symptoms, such as depression, is considered a relevant prognostic marker indicative of poor motor outcomes in Parkinson’s disease. Because motor symptoms only appear after marked degeneration of dopamine-producing neurons, scientists believe that significant motor system compensation occurs in these patients, providing a way to overcome dopamine loss.
Patients with de novo Parkinson’s — newly diagnosed and still untreated — with either olfactory dysfunction (loss of sense of smell) or rapid eye movement sleep behavior disorder have greater motor deficits than those without these symptoms, but they both have the same levels of dopamine, suggesting that the early presence of non-motor symptoms correlates with less compensatory ability.
The early occurrence of depression in de novo Parkinson’s indicates widespread involvement of pathological lesions, which may limit motor compensatory ability and lead to greater physical impairment. However, the link between depression and dopamine depletion in early Parkinson’s is still unclear.
Aiming to address this gap and to explore whether early occurrence of depression is associated with reduced motor compensation, researchers from Yonsei University College of Medicine in South Korea analyzed 474 patients, at a mean age of 64.6 years, including 242 men, with de novo Parkinson’s without dementia. The mean duration of their symptoms was 18.3 months.
The patients underwent positron emission tomography (PET) scans for the dopamine transporter (DAT) — responsible for the uptake of dopamine into neurons from the synapse, where neurons communicate — in the striatum, a key brain region involved in movement and cognition.
Depression was assessed using the Beck Depression Inventory, a 21-question multiple-choice self-report inventory composed of items related to symptoms of depression. Motor symptom severity was evaluated with Part III of the Unified Parkinson’s Disease Rating Scale, and the Mini-Mental State Examination was used to measure cognitive function.
Depression scores were divided into three levels: 157 patients, 55.4% of whom were women, were in the highest (worse) level (a score of 15 or greater, assumed to include only depressed patients); 159 patients, of whom 49.7% were women, were in the middle level (a score of 8-14); and 158, of whom 41.8% were women, were in the lowest level (7 or less, non-depressed patients only).
Patients in the highest level had more severe motor impairment and worse cognitive function than those in the lowest levels, even after taking DAT scan results into account.
Of note, no differences were found in DAT scores across the three groups, suggesting that “depression in de novo [Parkinson’s] does not require striatal dopamine depletion,” the researchers wrote.
Over a median follow-up of 47 months — ranging between four and 107 months — two movement disorder specialists adjusted the doses of Parkinson’s medications at three-to-six-month intervals.
Depressed patients required higher levodopa-equivalent doses — the amount of levodopa that has a similar effect as the medication taken — than non-depressed individuals after taking age, gender, and initial

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