People With Bipolar Disorder Face Higher Risk of Later Developing Parkinson’s, Study Finds

bipolar disorder

People with bipolar disorder have a significantly increased risk — more than three times that of the general population — of later developing Parkinson’s disease, a study has found.

Although use of medications for bipolar disorder could overestimate this risk, the researchers believe that a Parkinson’s diagnosis should be considered if patients with the mental health condition also show parkinsonian features.

The study, “Risk of Developing Parkinson Disease in Bipolar Disorder – A Systematic Review and Meta-analysis,” was published in JAMA Neurology.

Biopolar disorder is a mood disorder characterized by cyclic episodes of depression and mania. Although the mechanisms underlying bipolar disorder are still not completely understood, there is a possible role of the dopaminergic system — which is affected in Parkinson’s disease.

In fact, antipsychotic medications that block dopamine receptors can improve manic symptoms in these patients.

Certain medications used to treat bipolar disorder — such as lithium, antipsychotic medications, and antiepileptic medications — could be associated with drug-induced parkinsonism, which cannot be effectively distinguished from Parkinson’s disease in the clinic.

“Since drug-induced parkinsonism is more common among patients with [bipolar disorder], physicians may be more inclined to misdiagnose PD as drug-induced parkinsonism,” the researchers said.

Some studies also have shown that bipolar disorder is more common in people with Parkinson’s.

To understand the possible association of bipolar disorder with a later diagnosis of idiopathic Parkinson’s disease — meaning it’s due to an unknown cause — researchers from the University of Lisbon in Portugal performed an electronic literature search across four medicine-related databases.

Data from seven studies, involving 4, 374, 211 total participants, were used. The selected studies contained data on the likelihood of developing Parkinson’s disease in individuals with bipolar disorder versus those who did not have this condition.

The results showed that those with bipolar disorder were 3.4 times more likely to develop Parkinson’s disease later in life. Even when accounting for studies that had a high risk of bias, this likelihood was still maintained, albeit lower, at 3.21 times greater risk.

Researchers then performed a subgroup analysis in which they divided participants based on the duration of their follow-up. Specifically, they split patients into two groups: one including participants with more than nine years of follow-up versus those who were followed for less time.

Both groups had an increased risk of developing Parkinson’s, but the subgroup with the shorter follow-up was associated with a greater increase in the risk of a PD diagnosis.

However, this could be due to a higher rate of misinterpretation of drug-induced parkinsonism as Parkinson’s disease. “In fact, one study explicitly did not differentiate between the 2 conditions,” the researchers said.

“This review suggests that patients with [bipolar disorder] have a significantly increased risk of developing PD compared with the general population,” the researchers said.

They added that, if patients with bipolar disorder show parkinsonism features, a Parkinson’s diagnosis should be considered “independently of concomitant medication.”

The investigators said further testing could help to determine whether patients presented Parkinson’s versus drug-induced parkinsonism.

“To clinically distinguish parkinsonism from PD in clinical practice, the use of functional neuroimaging methods may be of particular interest,” they said.

“The main clinical implication of this review should be to underline that if patients with [bipolar disorder] present with parkinsonism features, this may not be drug induced and may recommend the investigation of PD,” the researchers concluded.

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Updated Canadian Guideline Reflects Latest Advances and Adds Palliative Care Section

Canadian Guideline Parkinson's

Updated recommendations on Parkinson’s disease have been published in the Canadian Guideline for Parkinson Disease, which includes a new section about palliative care.

Focused on issues relevant to the Canadian healthcare system, the update reflects the latest evidence and advances — particularly regarding diagnostic criteria and treatment options — and draws on recommendations from the United States, Scotland, the United Kingdom, and the European Union.

The Parkinson Canada-funded publication, which was published in the Canadian Medical Association Journal, offers fundamental guidance to healthcare professionals, patients, and families, and was developed with help from experts in Canada from various disciplines.

“This guideline provides evidence-based recommendations to improve the overall standard of care of individuals with Parkinson disease in Canada, not only for healthcare professionals, but also for policy makers, patients themselves, and their caregivers,” Veronica Bruno, MD, a neurologist with a subspecialty in movement disorders at the University of Calgary, said in a news release. “Managing the complexity of Parkinson disease requires clear, standardized procedures that can be used by all actors involved.”

The new guideline has five sections: communication, diagnosis and progression, treatment, non-motor features, and palliative care, which was added in this update. Palliative care, including an option of medically assisted death, should be considered throughout the course of the disease, the publication states.

“End-of-life choices, including advanced care planning with an open and frank discussion with the patient and the person designated as decision-maker, should be initiated early in the disease process,” the guideline says. “Conversations occurring in the ambulatory setting are likely to be more productive and less crises-driven than leaving such conversations until an acute stay in hospital.”

Other highlights include:

“A limitation to implementing the guideline is the lack of access to health care providers experienced in caring for people with Parkinson disease,” David Grimes, a neurologist at The Ottawa Hospital, said.

“In addition to specialist physicians, we need more nurses, and speech, occupational and physical therapists with training in this area, as well as adequate palliative care for Parkinson patients,” he added.

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Grant Will Help Develop Non-Invasive Skin Test for Diagnosing Parkinson’s

diagnostic skin test

Scientist Wenquan Zou, MD, PhD, has received a two-year grant to develop a non-invasive skin test for diagnosing Parkinson’s disease, Alzheimer’s disease, and other neurodegenerative disorders.

Diagnosing these disorders currently requires invasive analysis, either by imaging brain tissue or analyzing the cerebrospinal fluid (CSF) — the liquid surrounding the brain and spinal cord — for disease biomarkers. These are biological substances that can be measured to indicate a medical condition or disease.

Changes associated with Parkinson’s, and other neurodegenerative diseases, begin to occur around two decades before people develop symptoms, researchers say. An earlier diagnosis could allow individuals to receive treatment early in the disease process.

In Parkinson’s, the accumulation of abnormal (misfolded) alpha-synuclein protein leads to the formation of toxic aggregates, or clumps, that in turn lead to the death of dopaminergic neurons. Those neurons are responsible for producing dopamine, a substance produced in response to nerve signals that acts as a chemical messenger.

These toxic clumps are the main component of Lewy bodies and Lewy neurites found in the brains of Parkinson’s patients.

The potential test could help identify those at risk for Parkinson’s by detecting the presence of misfolded alpha-synuclein proteins in the skin.

“In addition to early diagnosis, pinpointing the misfolded proteins in more accessible specimens such as the skin can be used for effectively monitoring disease severity and evaluating the therapeutic value of new treatments for Alzheimer’s and other neurodegenerative diseases,” Zou, associate director of the National Prion Disease Pathology Surveillance Center, at Case Western Reserve University School of Medicine, said in a press release.

While certain lab tests and microscopy techniques can detect the presence of misfolded alpha-synuclein in the skin, these still have variable levels of sensitivity. That renders the diagnoses unreliable, make these inconsistent as diagnostic tools.

The proposed test uses a newly developed technology — called real-time quaking-induced conversion or RT-QuIC — to detect the presence of misfolded proteins in the skin.

In the new test, researchers mix a skin sample with the normal protein of interest, like alpha-synuclein. It is known that the presence of a misfolded protein can induce the aggregation of normal proteins. These clumps, in turn, trigger a fluorescent probe that emits a light that can be monitored in real time.

The skin test is highly sensitive and makes it possible to detect even small amounts of misfolded protein in the skin.

“Since skin biopsy is substantially less invasive than spinal tap [also called lumbar puncture, the invasive process to acquire a CSF sample] and brain biopsy, and because RT-QuIC is highly sensitive and specific and therefore more accurate than other lab-based methods, it is conceivable that the test represents a promising tool for diagnosing, characterizing, and predicting Alzheimer’s disease as well as Parkinson’s and other neurodegenerative diseases,” said Zou, also an associate professor in the departments of pathology and neurology at the Case Western School of Medicine in Ohio.

The same team had previously used the test to successfully detect misfolded proteins in the skin of people who died from Creutzfeldt-Jakob disease, sometimes called the human version of mad cow disease.

The new grant will allow the Zou and his team to confirm and extend these findings to Parkinson’s disease, and other neurodegenerative disorders.

Funding for the project is provided by the Alzheimer’s Association, Alzheimer’s Research UK, the Michael J. Fox Foundation for Parkinson’s Research, and the Weston Brain Institute. The grant award is for $149,729.00 over the course of two years.

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Overcoming the Grief Caused by Parkinson’s

Journeying Through Parkinson's

One thing that many people might not associate with experiencing Parkinson’s disease is grief. Experiencing grief with this disease is real. It can be felt deep down in your soul, whether you are the one who actually has the disease or you are the caregiver. You mourn for a life that used to be, and fear it may never be again.

Although our life changes in unexpected ways and fear threatens to consume our days and terrorize our nights, we can learn to overcome those wretched feelings. Innumerable people miss out on the rich experiences and blessings they have been given today because they can’t stop worrying about their future with Parkinson’s.

In “Living Beyond Your Feelings: Controlling Emotions So They Don’t Control You,” author Joyce Meyer writes, “The three most harmful negative emotions are anger, guilt, and fear.” When we have Parkinson’s disease, we are particularly susceptible to anger and fear. 

We experience anger, as evidenced when we ask ourselves the age-old question, “Why me?”

We pump our fists in the air and ask, “What did I ever do to deserve this?!” Our dreams of a better tomorrow feel as if they have been sucked dry and replaced with feelings that frighten us and worries we can’t seem to get under control. 

We think about what used to be: The days when we were able to work at a job we loved; the times when we could get down and play with our grandchildren; the summer vacations we took that used to reenergize us instead of wearing us out. Grief steps in and leaves us feeling fearful and despairing.

Two weeks ago, I lost someone dear to me. She was like a second mother to me. I babysat her daughter as a newborn. She was my maid of honor at my wedding. And when I think of her, a great sadness overcomes me: grief. It not only came upon me at the news of her passing, but also returns each time I think of her.

Getting a diagnosis of Parkinson’s disease can be like losing a loved one.

There is the initial grief, but waves of grief can still overcome us, sometimes when we least expect them. Often, those waves of grief are accompanied by fear. Not only are we dealing with what we’ve lost, but also we are fearful of what we may still lose.

Getting through grief over the loss of a loved one takes time, and the amount of time varies with each individual. It’s the same with the grief of having Parkinson’s. 

Grief is normal.

Grief is a part of life. While we must learn to accept it, it is still OK to cry. It is OK to mourn what we have lost. In that mourning, however, we need to remember that life goes on. While we may not know what tomorrow will bring, we know we have this moment right here, right now, and Parkinson’s can’t take that away.


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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Gut Alpha-Synuclein May Be Used as Biomarker of Parkinson’s, Study Suggests

Gut alpha-synuclein

Alpha-synuclein levels in the gut are linked to Parkinson’s disease, indicating that gut alpha-synuclein may be used in combination with other disease biomarkers to facilitate patients’ diagnosis, a review study found.

The study, “Diagnostic utility of gut α-synuclein in Parkinson’s disease: A systematic review and meta-analysis,” was published in Behavioural Brain Research.

Parkinson’s disease is associated with the overproduction of the protein alpha-synuclein in nerve cells of the brain. When this protein clumps together, it gives rise to small toxic deposits inside brain cells, called Lewy bodies.

Alpha-synuclein phosphorylation — a chemical modification in which a phosphate group is added to the protein — is known to occur in Parkinson’s disease, and is thought to be a critical step in disease progression as it enhances alpha-synuclein’s toxicity, possibly by increasing the formation of alpha-synuclein aggregates.

Some scientists think Lewy bodies form in the enteric nervous system (ENS) — the network of nerves that innervate the gastrointestinal tract — then spread to the brain, where they will gradually damage and destroy brain cells.

Although alpha-synuclein has already been detected in tissue samples collected from the stomachs and colons of Parkinson’s patients, its usefulness as a disease biomarker is still controversial.

Chinese researchers conducted a systematic review focused on assessing the relationship between gut alpha-synuclein and Parkinson’s, as well as its diagnostic power in distinguishing patients with the disease from those without it (controls). They reviewed 21 previously published studies reporting findings on gut alpha-synuclein, or phosphorylated alpha-synuclein.

Pooled data from the studies revealed that patients with Parkinson’s were approximately 10 times more likely to have deposits of alpha-synuclein in the gut compared to control subjects. This suggests a direct relationship between gut alpha-synuclein and Parkinson’s disease.

Further analysis showed that gut alpha-synuclein and phosphorylated alpha-synuclein could correctly identify 81.9% and 82.2% of individuals who did not have Parkinson’s disease. However, both had poor sensitivity and failed to distinguish patients with the disease from control subjects in approximately half the cases — a sensitivity of 56.8% for gut alpha-synuclein and 57.9% for phosphorylated alpha-synuclein.

“These results showed that a single measurement of gut [alpha]-synuclein could lead to the underdiagnosis of Parkinson’s disease,” researchers said. “This systematic review and meta-analysis confirmed a high degree of association between gut α-synuclein and Parkinson’s, which suggested that gut [alpha]-synuclein is a potential therapeutic intervention.”

Additional studies are still warranted to further explore the diagnostic potential of gut alpha-synuclein when combined with other biochemical markers of the disease, and “more efforts should be made to improve the standardization of current assays,” they said.

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Alabama Parkinson’s Patient Helps Raise Awareness, Especially in Black Community

Parkinson's advocate

The early signs can be subtle, and Parkinson’s disease is not a top-of-mind diagnosis for people younger than 50. So, Michael S. Fitts endured a battery of diagnostic tests with his primary care physician in Birmingham, Alabama, before seeking referral to a neurologist.

“I was in denial,” said Fitts, a black man who was 37 at the time. “I felt like whatever I was dealing with was a neurological disorder, but I didn’t think it was specifically Parkinson’s because I didn’t think people of color had this.”

For Fitts, the first recognizable sign was a slight, periodic hand tremor. Fitts was riding in a car in the summer of 2010, when his friend asked if he was cold. Fitts said he wasn’t. His friend commented on the tremor, which Fitts brushed off as something that happened every now and then. But the exchange prompted a year-long diagnostic journey before a neurologist eventually told him he had Parkinson’s.

Shaken and concerned about his future, Fitts sought a second opinion, which confirmed the diagnosis. At age 38, Fitts plunged into a state of depression and anxiety and getting out of bed became a daily challenge. As he struggled to come to grips with the disease, he told no one.

A specialist in movement disorders suggested a local support group for those with early-onset Parkinson’s. After overcoming his reluctance, Fitts realized it was the best thing he could have done. The group provided encouragement and shared tips on living with the disease as well as information on new research.

“Don’t isolate yourself because it will make your situation worse. Get someone to talk to,” he advised.

Creating a circle of support

Two years after his diagnosis, the tremors were becoming more obvious, and Fitts had difficulty holding a glass steady at workplace receptions. Fitts chose to share his diagnosis with his supervisor and colleagues at the University of Alabama at Birmingham (UAB) where he’s a medical librarian.

He said the decision to disclose Parkinson’s at the workplace is personal and individual. Patients should carefully consider how and what to tell colleagues.

Michael S Fitts
Michael S. Fitts (Photo by Sam Ogden)

An assessment at the Lakeshore Foundation, which partners with UAB on research, identified potential workplace accommodations, such as speech-to-text software. While Fitts doesn’t need such software now, he might later.

Fitts began to move from diagnosis to advocacy as he identified available resources and worked to expand support networks for others. He also convinced UAB’s Employee Assistance and Counseling Center to launch Hopeful Healing, a monthly support group for employees coping with any type of chronic illness.

In 2016, Fitts presented the opening session of a local Partners in Parkinson’s program. Hosted in 25 major U.S. cities, the events were an initiative of the Michael J. Fox Foundation (MJFF) and biopharmaceutical company AbbVie with the goal of providing educational resources to Parkinson’s patients and improving care at every stage of the disease.

“I don’t consider myself to be a public speaker, but I got a lot of positive feedback from the event,” Fitts recalled in a telephone interview with Parkinson’s News Today. “There are lots of ways to advocate, and whenever I can make an impact, I’ll do it, even if it means moving outside of my comfort zone.”

The event marked the beginning of Fitts’ work with MJFF, which led to him serving on the foundation’s Patient Council and filming the video series Parkinson’s 360º, “Getting to Know Parkinson’s Disease.”

“I personally love this series because of the diversity of participants,” Fitts said. “People need to see somebody they can identify with.”

As an African American, Fitts recognizes he is uniquely suited to serve as an advocate for both people with early-onset PD, as well as black Parkinson’s patients.

“We need to change the perception of Parkinson’s and demystify the whole perception of the disease as being associated with older white men,” said Fitts, now 46. “Part of it is giving people accurate information about the disease.”

The motor symptoms of Parkinson’s often immediately come to mind, but non-motor symptoms — loss of sense of smell, smaller handwriting, trouble sleeping, moving or walking — also can be important indicators.

“I want to bring awareness to Parkinson’s and what the symptoms are and how it affects people in different ways,” Fitts said. “If I would have known about some of the non-motor symptoms, such as a keen sense of smell, I probably would have sought medical attention earlier.”

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Alpha-Synuclein PET Tracers Identified with Potential to Track Parkinson’s Progression, AC Immune Says

alpha-synuclein PET tracers

Tracer compounds with high affinity and selectivity to alpha-synuclein deposits have been identified that could be used to detect and track Parkinson’s disease progression, AC Immune announced.

Findings were recently presented in the study, “Identification and Characterization of Selective and High Affinity Small Molecules for Positron Emission Tomography (PET) Imaging of Pathological Alpha-Synuclein,” during the 14th International Conference on Alzheimer’s and Parkinson’s Diseases and related neurological disorders (AD/PD 2019) in Lisbon, Portugal.

In the brains of Parkinson’s patients, there is a buildup of a protein called alpha-synuclein that forms clumps known as Lewy bodies, which are toxic and lead to neuronal death. Tau and beta-amyloid protein aggregates, commonly found in Alzheimer’s disease, are also known to play a role in Parkinson’s disease, but the exact mechanism remains elusive.

Clusters of misfolded alpha-synuclein proteins — meaning they are not in their correct structure — have been associated with disease severity.

There are noninvasive imaging techniques that allow researchers to visualize the metabolic processes in the body, such as the positron-emission tomography (PET) scan.

Developing new alpha-synuclein-specific PET tracers would allow scientists to study the distribution and the changes of the toxic clumps of alpha-synuclein protein as the disease progresses.

AC Immune screened its robust library of small molecules for suitable alpha-synuclein PET tracer candidates. This “molecular collection,” also known as the Morphomer platform, enables the identification of a new class of low molecular weight compounds, which, in turn, allows for the generation of small molecules — called morphomers — that specifically bind to misfolded proteins, working to break up the neurotoxic clusters and inhibit protein aggregation.

Researchers measured these molecules’ affinity to alpha-synuclein and selectivity over other protein aggregates (tau and beta-amyloid) in post-mortem samples from Parkinson’s and Alzheimer’s patients.

Several molecules exhibited high affinity, binding to alpha-synuclein present within neurons of Parkinson’s brain sections. These compounds were selective for alpha-synuclein aggregates over beta-amyloid and tau clusters.

Because a PET scan uses a small amount of a radioactive molecule, or tracer, to show differences between healthy tissue and diseased tissue, researchers radio-labeled these promising compounds with fluorine-18, a radioactive molecule.

They then evaluated these molecules’ ability to penetrate the brain as well their molecular fate within a living organism. Using non-human primates, they identified molecules with fast brain uptake and a rapid washout (meaning the biomolecule was rapidly eliminated from the body), which are the desired characteristics for a central nervous system PET tracer.

The identified alpha-synuclein PET tracer candidates will soon enter clinical trials for the imaging of pathological alpha-synuclein in Parkinson’s disease and other alpha-synuclein-related diseases.

“These data show the potential for what may be the first PET tracer for PD, which we are now moving into a Phase 1 trial,” Andrea Pfeifer, PhD, CEO of AC Immune SA, said in a press release.

“We believe that therapeutic developments coupled with the diagnostic tools needed to properly identify and select patients allow us to follow disease progression and confirm potential efficacy of therapeutic interventions. This will provide critical differentiation for our product-candidates and benefit patients with neurodegenerative diseases,” she added.

Besides these data on PET tracers, AC Immune and its partners presented six more studies on the potential role and discovery of other imaging tracers for Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), supranuclear palsy, and dementia.

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Particular Skin Smell May Help in Early Parkinson’s Diagnosis, Study Suggests

sebum smell Parkinson's

Parkinson’s disease (PD) could be identified through a noninvasive analysis of chemical components of sebum, the oily substance that helps keep skin and hair moisturized, a pilot study suggests.

The study, “Discovery of Volatile Biomarkers of Parkinson’s Disease from Sebum,” was published in the journal ACS Central Science.

In the early ages of medicine, a person’s odor was commonly used to help identify diseases. Although this method is no longer used, modern medical studies have associated some illnesses, in particular metabolic and infectious diseases, with specific smells.

One of the study’s co-authors, Joy Milne, the wife of a Parkinson’s patient who was diagnosed in 1986, has an extremely sensitive sense of smell, called a super smeller, and is able to recognize a particular odor associated with Parkinson’s disease. In preliminary tests, she identified this odor mainly in areas of high sebum production, such as the upper back and forehead.

Overproduction of sebum by skin sebaceous glands (a condition known as seborrhea) is a well-known non-motor symptom of the disease, and toxic forms of the protein alpha-synuclein — a Parkinson’s molecular hallmark — have been found in the skin of Parkinson’s patients.

“Identification and quantification of the compounds that are associated with this distinctive PD odor could enable rapid, early screening of PD as well as provide insights into molecular changes that occur as the disease progresses and enable stratification of the disease in the future,” the researchers wrote.

The team, led by researchers at the University of Manchester, further explored the potential of using smell and sebum analysis as a diagnostic tool for Parkinson’s disease.

They analyzed the volatile chemical components of sebum samples collected from 43 Parkinson’s patients and 21 healthy volunteers who were recruited at 25 clinical sites across the U.K.

These volatile components, which are often associated with odors, were detected by high-throughput chemical analysis as well as by olfactory pattern analysis, with the help of Milne.

Among the 17 particular compounds detected in Parkinson’s patients the team found 3,4-dihydroxy mandelic acid, which is a metabolite of L-dopa — one of the most commonly prescribed medications for Parkinson’s disease.

However, this compound was also identified in untreated patients. These findings suggest that changes in this compound could be indicative of other mechanisms rather than just therapy metabolism.

Further analysis revealed that the compounds perillic aldehyde and eicosane were significantly different between Parkinson’s patients and healthy controls. Perillic aldehyde levels were lower in Parkinson’s samples, while eicosane was present at significantly higher levels than in controls.

The presence of these compounds was consistent with the olfactory patterns of the specific “musky” smell of Parkinson’s.

Next, the team asked Milne to try to validate different mixtures of the identified compounds and compared them between patients and controls.

A mixture of all 17 identified compounds, or specific combinations of just nine or four of these compounds, were identified as being closer to the smell of Parkinson’s patients than healthy individuals.

These results were maintained regardless of whether patients had taken Parkinson’s medications or not.

“Now we have proved the molecular basis for the unique odor associated with Parkinson’s we want to develop this into a test,” Perdita Barran, PhD, a professor at the Manchester Institute of Biotechnology and senior author of the study, said in a press release.

“This could have a huge impact not only for earlier and conclusive diagnosis but also help patients monitor the effect of therapy. We hope to apply this to at risk patient groups to see if we can diagnose pre-motor symptoms, and assist with potential early treatment,” she added.

Main differences in perillic aldehyde and octadecanal levels could be associated with changes in fatty molecule metabolism in Parkinson’s disease. But they may also indicate altered activity of the natural bacteria that populate the skin of Parkinson’s patients.

“These potential explanations for the change in odor in PD patients suggest a change in skin microflora and skin physiology that is highly specific to Parkinson’s disease,” the researchers wrote.

More studies are still needed to further explore the potential of these volatile Parkinson’s biomarkers. In addition, studies with extended olfactory data from human smellers, as well as canine smellers, may help characterize in more detail the sebum odor pattern linked to Parkinson’s.

“Finding changes in the oils of the skin in Parkinson’s is an exciting discovery,” said David Dexter, PhD, deputy director of research at Parkinson’s UK. “More research is needed to find out at what stage a skin test could detect Parkinson’s, or whether it also occurs in other Parkinson’s related disorders, but the results so far hold real potential.”

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MRI Technique Helps Distinguish Between Parkinson’s and Progressive Supranuclear Palsy, Study Reports

MRI technique

A specific magnetic resonance imaging (MRI) measure can accurately predict the development of eye movement abnormalities, helping to identify patients who develop progressive supranuclear palsy with parkinsonism (PSP-P) after an initial diagnosis of Parkinson’s, a study shows.

The study, “Refining initial diagnosis of Parkinson’s disease after follow‐up: A 4‐year prospective clinical and magnetic resonance imaging study,” appeared in the journal Movement Disorders.

A clinical diagnosis of Parkinson’s may be inaccurate in the early stages of the disease, when its characteristic motor symptoms are not fully manifested. PSP-P has a similar clinical presentation to idiopathic Parkinson’s (of unknown cause), including bradykinesia (slowness of movement), limb rigidity, and tremor, leading to difficulty in differentiating between the two.

Recent diagnostic criteria defined probable PSP-P as vertical gaze abnormalities (VGA) — difficulty in moving the eyes up and/or down — associated with levodopa‐resistant parkinsonism, a term for neurological disorders that cause movement problems similar to those of Parkinson’s. However, patients with PSP-P may never develop VGA, meaning the prevalence of this disorder could be underestimated.

MRI has been a helpful tool to diagnose PSP and to predict the appearance of gaze abnormalities in people with PSP-P. A new version of the Magnetic Resonance Parkinsonism Index (MRPI), named MRPI 2.0, has shown high accuracy in distinguishing cases of Parkinson’s from those of PSP-P. The MRPI can be used in MRI studies to predict the presence of PSP in patients with clinically unclassifiable parkinsonism.

However, studies on the clinical features of PSP-P in patients initially diagnosed with Parkinson’s are still lacking.

To address this, researchers in Italy followed a group of 110 individuals — 73 of whom were men, with a mean age at examination of 62.9 years, and a mean disease duration of 4.4 years — with probable or possible Parkinson’s and 74 healthy individuals used as controls over four years.

The investigators conducted annual clinical evaluations to assess the appearance of VGA without early postural instability, which strongly suggests PSP‐P. MRI scans were performed at the beginning of the study and at the end of the follow-up period.

They also evaluated whether MRPI 2.0 helped predict the development of PSP-P in patients initially diagnosed with Parkinson’s.

At the start, 21 of 40 individuals with possible Parkinson’s and all 70 individuals with probable Parkinson’s were responsive to levodopa. Of all the patients, 100 retained their initial diagnosis, and 10 (9.1%) developed VGA and had their diagnosis changed to PSP-P, nine of whom only showed a moderate response to levodopa.

Specifically, all 10 patients whose diagnosis changed showed slowness of vertical saccades during follow-up, which refers to quick, simultaneous movements of both eyes that abruptly change the point of fixation. Vertical supranuclear gaze palsy (resulting from a cerebral impairment) in five patients was associated with higher imaging biomarkers values than slowness in vertical saccades. All 10 patients had at least three years of parkinsonism without postural instability.

All MRI measures — including MRPI and MRPI 2.0 — were significantly different between patients with Parkinson’s and those at PSP-P both at the start of the study and at the end of follow-up. At the beginning, MRPI 2.0 was the most accurate (100%) biomarker in predicting the appearance of VGA, “enabling [PSP-P] patients to be identified at the earliest stage of the disease,” according to the researchers.

Although the number of patients whose diagnosis was changed is small, the researchers said that their findings “demonstrate the usefulness of these new imaging biomarkers, and specifically of the MRPI 2.0, in predicting the development of VGA and the clinical evolution towards PSP phenotypes in patients with the initial diagnosis of [Parkinson’s].”

Most clinical variables — including motor function, assessed with the Unified Parkinson’s Disease Rating Scale–Motor Examination (UPDRS‐ME), and cognitive function, measured with the Mini-Mental State Exam — also showed a marked difference between the two groups at follow-up. However, clinical variables were less accurate than imaging biomarkers in predicting VGA.

Data further showed that disease progression was more signficant in patients with PSP‐P, as assessed with MRI and UPDRS‐ME.

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New Diagnostics for PD Might Allow Early Diagnosis, Prevention

Parkinson's diagnosis

A new way of diagnosing Parkinson’s disease based on manifestations that appear decades before motor symptoms — the current hallmarks for diagnosis — might allow early diagnosis and even prevention.

The study, “From Prodromal to Overt Parkinson’s Disease: Towards a New Definition in the Year 2040,” was published in the Journal of Parkinson’s Disease.

Parkinson’s disease is characterized by progressive loss of coordination and movement. Currently, a person is diagnosed when those symptoms appear. However, there are some risk factors and symptoms that precede motor manifestations and constitute the early stages of the disease (called prodromal).

“Brilliant work of many in different scientific fields has paved the way for the concept of prodromal  [Parkinson’s disease]; that is, a phase of years to decades in which non-motor and subtle motor symptoms may indicate spreading PD pathology, but do not meet the threshold for diagnosis according to the classic motor-based clinical criteria,” researchers said.

The development of new diagnostic criteria that allow the identification of prodromal Parkinson’s might help to better understand disease progression, lead to early diagnosis and treatment, and prevent classic motor symptoms.

Now, Parkinson’s experts Daniela Berg, MD, Christian-Albrechts-University of Kiel, Germany, and Ronald B. Postuma, MD, MSc, Montreal General Hospital, Canada, have developed a mathematical model that calculates a person’s risk of being in the prodromal phase of the disease. This model is based on three main premises relative to Parkinson’s prodromal phase:

  • The fact that the neurodegenerative process in Parkinson’s is slow and continuous, possibly starting in the gut or olfactory system, finally reaching the nervous system;

  •  The increased knowledge regarding risk factors and clinical symptoms that occur years or decades prior to motor manifestations. These can be correlated to imaging findings and tissue examinations;

  • Studies have found that people who manifest different combinations of risk and prodromal markers can many times progress to Parkinson’s disease.

Currently, however, the model has some limitations. For example, it does not consider age and sex factors, and cannot predict whether or when motor symptoms will appear.

“The prodromal PD criteria are meant to be research criteria and constitute a first step in what should be a continually updated process,” researchers stated.

New Parkinson’s biomarkers — substances present in the body that indicate the occurrence of a condition — are continually being discovered, providing new information that makes the model more reliable. In time, the hallmarks for diagnosis might be based on the presence of biomarkers instead of motor symptoms.

Wearable technology, such as mobile phones, also allows the continuous capture of movement in daily life, which will benefit “from new methods of data handling and analyses,” researchers said.

“With new data arising from objective movement measurements, the earlier detection of motor symptoms will become possible. Objectively measured markers … wearable-based markers of activity … indicate that we can expect to change our understanding of early motor PD,” researchers said.

The model will be available online, allowing doctors to calculate the risk for patients. Additionally, there will be a platform where experts can share information and discuss the new criteria for diagnosis.

With this collaborative model, researchers expect to incorporate the new criteria and have a functional model by 2040. This is expected to allow early diagnosis and treatment and, in time, prevention of clinical symptoms.

“Our review highlights the importance of making an earlier diagnosis of neurodegenerative diseases, and in particular PD, for now primarily to understand the disease better,” Berg and Postuma said in a press release. “However, in the future, once we have preventive therapy, it will become critical to find patients in the earliest stages of the disease so that we can prevent the disease from developing and affecting quality of life.”

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