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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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Parkinson’s Subtypes May Predict Disease Course and Survival, Study Suggests

Parkinson's subtypes

Subtyping Parkinson’s disease at diagnosis may predict disease course and survival, providing both doctors and patients with a more accurate prognosis, a study suggests.

The study, “Prognosis and Neuropathologic Correlation of Clinical Subtypes of Parkinson Disease,” was published in JAMA Neurology.

Parkinson’s disease is characterized by clinical diversity, and many attempts have been made to identify distinct clinical syndromic patterns. The presence of not only motor but also non-motor symptoms is increasingly being used to categorize the disease into different clinical subtypes.

However, “classification of patients with [Parkinson’s disease] is purely based on data association and may not reflect underlying [physiological processes associated with disease] driving clinical heterogeneity,” the researchers wrote.

Although very little is known about the correlation between brain tissue molecular/cellular changes and Parkinson’s subtypes, some studies suggest that motor severity, cognitive impairment, autonomic dysfunction — when the nerves of the system that controls basic bodily functions are damaged — and rapid eye movement (REM) sleep behavior disorder need to be taken into consideration during clinical subtyping. (REM is a sleep stage in which the eyes move rapidly in various directions.)

Moreover, the predictive value of Parkinson’s-related subtype classification remains to be confirmed.

For this purpose, investigators from the University College London Queen Square Institute of Neurology gathered life-course clinical and brain tissue analysis data and correlated it with Parkinson’s disease subtypes.

They analyzed the clinical records of 111 Parkinson’s patients, 60.4% of whom were men, who were regularly assessed throughout their disease and had their diagnosis confirmed by autopsy.

According to the severity of their motor symptoms, REM sleep behavior disorder, cognitive performance, and autonomic function at diagnosis, the patients were classified into three subtypes: mild-motor predominant (meaning they had mild motor and non-motor symptoms), diffuse malignant (severe symptoms), or intermediate (where they did not meet the criteria for the other two subtypes).

Researchers calculated the time it took patients to achieve specific disease milestones (recurrent falls, wheelchair dependence, dementia, and care home placement) and compared them between subtypes. They also assessed time from diagnosis to death.

In addition, post-mortem analysis of brain tissue was performed to assess the severity and distribution patterns of Lewy bodies — abnormal deposits of alpha-synuclein protein — and Alzheimer’s disease-related tissue changes.

Of the 111 participants, 54 were classified as mild-motor predominant, 39 as intermediate, and 18 as diffuse malignant.

Patients with the mild-motor predominant subtype were significantly younger at diagnosis, had a better response to levodopa, and received a higher levodopa equivalent dose. In contrast, those with the diffuse malignant subtype were older, had a poorer response to levodopa, and were more frequently misdiagnosed as having an atypical parkinsonian syndrome during their lifetime.

Age at diagnosis was significantly different across Parkinson’s subtypes: mild-motor predominant — 58.2 years, intermediate — 65 years, and diffuse malignant — 70.3 years.

Patients’ ages at diagnosis were also associated with faster disease progression and reduced survival: The later they were diagnosed, the faster the disease progressed.

All Parkinson’s subtypes showed different rates of deterioration, “with the diffuse malignant subtype reaching all prognostic milestones earlier in the disease course and having the shortest survival,” according to the researchers.

Additionally, all subtypes “reached advanced stages, with 105 of 111 patients (94.6%) reaching at least one disease milestone,” they said.

Brain tissue analysis revealed distinct progression rates of Lewy body and Alzheimer’s disease-related pathologies, which were found to be associated with age at death. However, there were no significant differences across subtypes regarding severity of Lewy pathology.

“Clinical subtyping of [Parkinson’s disease] … is feasible in clinical practice and provides accurate long-term estimation of disease progression and survival. Different pathologies with differing rates of progression are important determinants of clinical subtypes, and age at diagnosis should be included in future subtype classification systems,” the researchers concluded.

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Taste, Smell Impairments May Help Identify People at Risk for Parkinson’s, Study Suggests

taste and smell impairment

Impaired sense of smell or taste can raise a person’s risk of developing Parkinson’s disease 2.5 times, a study suggests.

The study, “Incidence of Parkinson’s disease in a large patient cohort with idiopathic smell and taste loss,” was published in the Journal of Neurology.

Currently, Parkinson’s disease is diagnosed mainly on the assessment of patients’ motor symptoms and their severity. However, evaluation scales can be subjective and might fail to detect small changes.

Non-motor symptoms have gained increased attention because of their potential to anticipate Parkinson’s-related motor manifestations. Approximately 90% of Parkinson’s patients have altered smell sensitivity during the disease’s initial and moderate stages, thought to be partly because of brain connectivity changes.

To explore the incidence and diagnostic potential of smell and taste disorders in Parkinson’s disease, researchers reviewed the clinical records of 474 people who had been diagnosed with smell and taste loss of unknown cause.

Patients diagnosed and followed over a period of 15 years at the Smell and Taste Clinic in Dresden, Germany, were interviewed by phone using a standardized questionnaire to record their condition and clinical history.

At the time of the first assessment at the clinic, patients had already experienced reduced or lost  odor and taste sensitivity for a mean period of 4.6 years. Onset of olfactory (smell) disturbances was in general noticed at a mean age of 57.9 years; gustatory (taste) disorders, 59.3 years.

Of the 474 participants, 14.3% had a normal sense of smell, 40.5% had reduced, and 45.1% had complete loss of smell. Regarding taste, 90.1% of the participants had normal sensation, 9.5% had reduced, and 0.4% had complete loss of taste.

Collectively, 242 people were diagnosed with a qualitative olfactory or gustatory disorder, of whom 21.1% had parosmia (distortions of the sense of smell), 32.9% had phantosmia (olfactory hallucinations), and 7.6% had parageusia (distortions of the sense of taste).

Participants’ clinical reports revealed that 45 (9.5%) had developed Parkinson’s disease after the initial idiopathic smell and/or taste loss diagnosis.

Six of the Parkinson’s patients had combined olfactory and gustatory disorders at the time of diagnosis, whereas 38 had pure olfactory disorders and one patient had a pure gustatory disorder.

The frequency of taste disorders was similar between those with and without Parkinson’s. In contrast, Parkinson’s patients had a higher prevalence of initial complete loss of smell compared to those without the disease.

The team did not find a significant association between taste or smell loss and the development of the disease. Still, patients who developed Parkinson’s reported a decrease in olfactory and gustatory function more frequently than non-Parkinson’s patients.

Researchers found that “patients with a decrease in olfactory or gustatory function developed Parkinson’s with a significantly higher rate compared to patients with a stable smell or taste function.” Overall, impaired smell or taste sense increased the risk of developing Parkinson’s disease 2.47 times.

“Risk stratification might be considerably improved by correct diagnostic allocation of smell and taste loss, the use of both olfactory and gustatory testing, and subsequent long-term monitoring of these functions,” researchers said.

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Analysis of Tiny Vesicles Released by Red Blood Cells May Help Identify Parkinson’s Patients, Study Shows

extracellular vesicles

A new blood-based analysis that evaluates the levels and content of tiny vesicles released by red blood cells may help diagnose patients with Parkinson’s disease according to disease stage, researchers suggest.

The new method was described in the study, “Portrait of blood-derived extracellular vesicles in patients with Parkinson’s disease,” published in Neurobiology of Disease.

Parkinson’s disease is linked to a broad spectrum of clinical manifestations and several molecular mechanisms.

This represents a challenge for the development and identification of useful biomarkers for diagnosis and disease progression, as well as to track the effectiveness of new treatments.

All human cells produce tiny vesicles containing fatty molecules, proteins, and genetic information, which they release to the surrounding environment. These so-called extracellular vesicles are produced both in healthy and disease conditions, and are used by cells to communicate among themselves.

Given the major role these extracellular vesicles may have, researchers hypothesized that their cargo could hold useful information on the biological state of the body, representing a possible new diagnostic tool.

To this end, Canadian researchers developed a new method of isolating extracellular vesicles from blood samples that would preserve their integrity, while still removing any potential contaminants.

Using flow cytometry, a technique that allows the visualization and sorting of cells and small particles according to their size and shape, the team could identify not only extracellular vesicles but also which cells originated them. After the vesicles were isolated, the team could analyze their content.

Following the assay’s optimization, the team analyzed blood samples collected from 60 Parkinson’s patients and 37 age- and sex-matched healthy volunteers.

They found that Parkinson’s patients had about 1.8 times more extracellular vesicles released by red blood cells than healthy controls. However, upon further analysis, the team found that only five patients were responsible for this significant difference, implying that the number of extracellular vesicles could not be used to differentiate between Parkinson’s patients and healthy controls.

The quantity of extracellular vesicles released by other blood cell types was similar between groups.

When researchers analyzed vesicle numbers in regards to patients’ disease severity status — measured by total scores on the Unified Parkinson Disease Rating Scale (UPDRS) — they found that at least 87% of the variation in the total number of red blood cell-derived vesicles was due to a variation in UPDRS scores.

To validate their results, the team used the same analysis approach in a new set of blood samples collected from 42 Parkinson’s patients. Once more, they found they could use the number of red blood cell-derived extracellular vesicles to distinguish between patients according to their UPDRS scores.

Analysis of the content of the isolated vesicles revealed a total of 818 proteins, eight of which were found in significantly different amounts between controls and patients, allowing researchers to group individuals according to stages of disease (control, mild Parkinson’s, and moderate Parkinson’s).

“Our study shed light on a potential biomarker indicative of disease stage, which is derived from 2 measures: the number of [red blood cells-derived extracellular vesicles] and the expression of 8 different proteins,” the researchers wrote.

Although the analysis and isolation of extracellular vesicles through flow cytometry may not be accessible to all laboratories, “identification of specific proteins that match clinical stages of Parkinson’s” could be performed using simple and less expensive techniques, according to the researchers.

“The ability to develop a biomarker that not only works as a diagnostic tool but a predictor of disease stages/course would represent a major breakthrough in the field, opening up to new therapeutic opportunities,” they concluded.

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15 CSF Proteins Seen as Possible Biomarkers of Early Parkinson’s Fail at That Task, Study Reports

Parkinson's and biomarkers

Proteins in the cerebrospinal fluid that were seen as possible diagnostic biomarkers of Parkinson’s disease cannot serve in this role, because they lack robustness and reproducibility in earlier stages of the disease, a study has found.

The study, “Evaluation of cerebrospinal fluid proteins as potential biomarkers for early stage Parkinson’s disease diagnosis,” was published in PLOS One.

Parkinson’s is a chronic and progressive neurodegenerative disorder, mainly caused by the gradual loss of dopaminergic neurons in the substantia nigra, a region of the brain responsible for movement control. It is typically diagnosed based on the presence of motor symptoms, but these can be difficult to determine as disease-causing in Parkinson’s earlier stages.

Previous studies have suggested that specific proteins in the cerebrospinal fluid (CSF) —  which circulates in the brain and spinal cord — could work as early signals, or biomarkers, of disease to assist in a diagnosis. But CSF proteins have never been fully validated as Parkinson’s biomarkers in a clinical setting.

Researchers in Belgium, Germany, and the U.K. tested the suitability of 15 CSF proteins proposed as potential biomarkers for an early stage Parkinson’s diagnosis.

The panel of proteins explored were beta-amyloid (Aβ40 and Aβ42), alpha-synuclein (α-syn), tau (p-Tau and t-Tau),  neurofilament light chain (NFL), interleukin 6 (IL-6), protein deglycase (DJ-1), S100β (a calcium-binding protein), osteopontin (OPN), high-mobility group box 1 (HMGB1), ubiquitin carboxyl-terminal esterase L1 (UCHL1), Fms-related tyrosine kinase 3 ligand (FLT3LG), matrix metalloproteinase 2 (MMP2) and apolipoprotein A-I (ApoA1).

Researchers began by measuring the levels of these CSF proteins in a group of 80 patients with early stage disease and 80 healthy people serving as controls. Out of the 15 CSF proteins tested, six — α-syn, DJ-1, Aβ42, S100β, p-Tau and t-Tau — were significantly dysregulated among patients.

“Aβ42, t-Tau, p-Tau, α-syn and DJ-1 were decreased in early clinical PD [Parkinson’s disease] patients compared to the controls, whereas S100β levels was increased in early clinical PD patients,” the researchers wrote.

To confirm these candidates, researchers next performed this same test in an independent group of 30 Parkinson’s patients with advanced disease and 30 healthy controls. Here, a type of beta-amyloid, Aβ42, was the only CSF protein whose levels were significantly different — significantly lower — in Parkinson’s patients compared to controls.

“Decreased Aβ42 levels in CSF samples from PD patients had been reported recently, suggesting it may be a reliable candidate. However, in this study … analysis showed that this potential marker was not suitable for diagnostic purposes,” the researchers wrote.

Finally, to assess whether a combination of these markers could distinguish early Parkinson’s patients from healthy individuals, they used a machine learning approach based on an algorithm to identify markers that might improve disease diagnosis. Based on this model, a set of markers comprising α-syn, S100β, and UCHL1 were identified as promising candidates.

“[T]his model aligned with findings published in the literature, where α-syn is characterized as the hallmark protein of PD, closely involved in the progression of neuronal degeneration and subsequent motor impairments, while S100β has been considered a possible marker for the accompanying neurodegeneration,” the researchers wrote. However, “the decision tree could not be confirmed” in the second group of patients and controls.

“[C]urrently proposed protein CSF markers for PD diagnosis, as identified in late stage PD cohorts, lack robustness and reproducibility when applied in the early clinical stages of (…) PD,” they added.

The researchers believe that further efforts, including the EU-BIOMARKAPD project that is exploring alternative approaches to biomarker identification, may support the development of potential protein CSF biomarkers for clinical diagnosis or disease monitoring in early stage Parkinson’s disease.

The post 15 CSF Proteins Seen as Possible Biomarkers of Early Parkinson’s Fail at That Task, Study Reports appeared first on Parkinson’s News Today.

The ABCs of Parkinson’s: ‘F’ Is for ‘Fear’

fear

Sherri Journeying Through

Editor’s note: A continuation of the “ABCs of Parkinson’s” series.

“You have Parkinson’s disease.”

“What exactly does that mean?” I asked.

While I waited for a response to my question, my thoughts covered a multitude of fears in a minimal amount of time. I sat and listened to my doctor’s explanation, which began sounding like background noise. I answered no to the question of whether I had any questions, when in fact I had multitudes but didn’t want to hear the answers for fear of what they might be. I was loaded with a sample starter of Mirapex (pramipexole) and something else I can’t remember for lack of paying attention. Then, I said thank you, scheduled the next visit, and left. 

“It’s gonna be OK,” my husband tried reassuring me later at home. But, how did he know what OK looked like and if I was going to like the picture?

I know as well as the next person that fears are normal. They can be both healthy and destructive. I know fear is common among people with Parkinson’s disease. As I began learning more about PD and acquiring information about the disease, I saw that fear was not only a real part of Parkinson’s but something that was rarely ever mentioned, let alone discussed. Were we supposed to be brave on the outside while we were shaking like crazy on the inside?

I had a professor in college who said it’s not that we fear the dark but that we fear the things we cannot see in the dark. I suppose you could then say — as a person with a chronic disease — that we often find it easy to “live in the dark,” as this disease manifests itself with things we can’t see. Things we didn’t know would be coming. We aren’t so much afraid of Parkinson’s disease or having it. It is safer to say that we fear what Parkinson’s could, can, and will do to us. 

My edition of Merriam-Webster defines fear as “a reason for dread … taking the form of terror, horror, panic, alarm, dismay, consternation, and trepidation.” Yep. I’d say those terms fit. 

Fear can be my greatest enemy in this journey with Parkinson’s disease. It can cause anxiety at every level. Honestly, dread, terror, panic, dismay, and consternation have all had their heyday with my mind when it comes to this disease.

At times in my life, I have felt powerless because of this disease. I have experienced moments of terror when an intense, overpowering fear has swept over me and consumed my thoughts with the what ifs. Panic has seized me in the most unexpected moments: seeing a person in a wheelchair, a woman who shuffles into the store in front of me, an older man who drops his coffee mug because his hand is shaking. There are reminders all around that cause me to panic and be reminded that this could be me in five months, or two years, or six days, or …

I have been dismayed and at times have lacked the courage and the power to fight this monster. I have felt paralyzed by the confusion of what to do next, helpless in this new battle I was chosen for, and afraid that I may not know how to fight well, or may not have the necessary weapons.

What do you do with that feeling of helplessness and dread? What do you do when panic consumes your life and leaves you exhausted and powerless?

I can’t accomplish much of anything when I’m feeling overwhelmed, and my mind is confused and cluttered. Eventually in my struggle, I remember and believe that the God who made me will not allow this trial to consume me, nor will He leave me defenseless to fight it alone. Some say that religion or God is for those who are weak. You can call me weak.

There is comfort in knowing that I don’t face the battles of this disease alone. The unknowns. The what ifs. If I truly believe what I write, then I can step out and do what often seems impossible to do in the darkest valleys: face my fears. What makes that possible is faith. And it is faith that gives us hope.

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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.

The post The ABCs of Parkinson’s: ‘F’ Is for ‘Fear’ appeared first on Parkinson’s News Today.

Source: Parkinson's News Today