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Higher Risk of Falls Linked to Longer Disease Duration and PIDG Subtype, Study Suggests

gene mutation cancer risk

In Parkinson’s patients, the risk of falls increases depending on disease duration and having the postural instability/gait disturbance (PIDG) subtype, but is not signficantly correlated with non-motor symptoms, a study suggests.

The study, titled “Falls in persons with Parkinson’s disease: Do non-motor symptoms matter as much as motor symptoms?,” was published in Arquivos de Neuro-Psiquiatria.

Falls can be a major problem for people with Parkinson’s disease, with some individuals being at greater risk of serious falls. However, identifying a person’s fall risk can be challenging because the risk is affected by a multitude of different factors that may or may not be related to Parkinson’s disease itself.

Intuitively, it may seem that the best predictors of falls are likely related to motor symptoms — after all, falling is associated with moving. But, previous studies have suggested that measurements of motor function aren’t good predictors of falls.

The researchers behind this new study set out to investigate whether including non-motor symptoms, in addition to motor symptoms, would help better predict fall risk in people with Parkinson’s.

To test this, the researchers assessed 179 people (average age of 64.6 years, mean disease duration of 10.4 years) with Parkinson’s who were seen at the National Institute of Neurology and Neurosurgery in Mexico City. The participants’ clinical history, including fall history in the past year, was taken.

Participants underwent a series of evaluations, including disease state using the Hoehn and Yahr scale, assessment of motor symptoms using relevant parts of the Movement Disorders Society Unified Parkinson’s Disease Rating Scale, as well as non-motor symptoms using the Non-Motor Symptoms Scale.

Overall, 16.8% had experienced a fall in the last year, with just over half of these having experienced more than one fall — the average was 2.5 falls per month. The researchers noted that this is a “very low” proportion of patients who experienced falls (“fallers”), which “could partially be explained by under-representation of advanced forms of the disease,” a limitation of the study.

The researchers constructed statistical models using several types of data that they had collected, with the aim of identifying factors that were significantly over-represented among the fallers — thus, being predictive of falling.

They found that the severity of motor and non-motor symptoms in the participants was not significantly linked with fall risk.

However, the study did find two factors that were linked with fall risk: the first was disease duration. Patients who had experienced symptoms for longer were more likely to fall — average disease duration was 12.8 years in the fallers group and 7.4 years in the non-fallers group.

The second risk factor was having the PIDG subtype (which accounted for 59.8% of the participants), one of the three groups into which Parkinson’s patients can be divided based on their most prominent motor symptoms. The PIDG subtype is associated primarily with difficulty standing and/or walking and is thought to be associated with rapid progression of disease and cognitive dysfunction.

While about half (53%) of the people in the non-fall group had the PIDG subtype, nearly all (93%) of those in the fall group had the subtype.

“Disease duration and the PIGD subtype were identified as relevant risk factors for falls in [people with Parkinson’s disease]. Non-motor symptoms appear to have a less important role as risk factors for falls,” the researchers wrote, adding that these findings suggest a need for a “more intensive approach in fall prevention” for people with this subtype.

 

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Atrophy in Thalamus Linked to More Severe Non-motor Problems in Parkinson’s Patients

brain regions

People with severe non-motor symptoms related to Parkinson’s disease (PD) have a smaller thalamus compared to those with similar but mild to moderate symptoms, a brain imaging study suggests.

Sleeping and gastrointestinal problems are also tied to atrophy (shrinking) of the thalamus, a part of the inner brain known to process motor signals and to regulate consciousness, alertness, and sleep.

The study, “Sleep disturbances and gastrointestinal dysfunction are associated with thalamic atrophy in Parkinson’s disease,” was published in the journal BMC Neuroscience

Parkinson’s is marked by a progressive loss of coordination and movement. In addition to difficulties in movement (motor symptoms), it can cause a variety of non-motor symptoms such as sleep problems, depression, gastrointestinal and urinary problems, and difficulty thinking (cognitive impairment).

Techniques such as magnetic resonance imaging (MRI) help to diagnose PD through brain scans, and they can also help identify structural changes in the brain — like changes in thickness or volume — associated with its non-motor symptoms.

But the exact location of specific brain areas linked to non-motor symptoms is still unclear. 

Researchers recruited 41 patients diagnosed with idiopathic (unknown origin) PD at the Movement Disorders clinics at King’s College Hospital in London. All were analyzed through MRI brain scans.

None of these patients chosen showed signs of mild PD cognitive impairments or disease-related dementia, and they had no history of neurological or psychiatric disorders.

Patients were first assessed by medical staff using the Non-motor Symptoms Scale for PD (NMSS), then self-assessed using the Non-motor Symptoms Questionnaire (NMSQ). The Beck Depression Inventory-II (BDI-II) and the Hamilton Depression Rating Scale (HDRS) evaluated neuropsychiatric symptoms.

Motor symptoms stages were determined with the Hoehn & Yahr (H&Y) scale, general cognitive status was assessed using the Mini Mental Status Examination (MMSE), and quality of life (QoL) was measured by patients completing the 39-item PD Questionnaire (PDQ-39).

All were required to stop taking dopamine-related medications the night before the scans to avoid involuntary movements caused by side effects. 

Patients were then divided into two groups based on their NMSS scores. A total of 23 patients who scored 40 or below were considered to have mild to moderate non-motor Parkinson’s symptoms, while 18 who scored 41 or above were defined as severe. 

Results showed that, compared to those with mild to moderate symptoms, those with severe non-motor symptoms were older, had the disease longer, were using higher doses of medication, had higher H&Y scores, and reported a lower QoL. Severe non-motor PD patients also scored more poorly in the sleep and fatigue sections of the NMSS. 

MRI scans were taken, and the cortical (outer brain) thickness and subcortical (inner brain) volumes were calculated and compared with patient assessments.

Analyses revealed that the inner brain’s thalamus was significantly smaller in volume (thalamic atrophy) in PD patients with severe non-motor symptoms, compared to those with mild to moderate symptoms. 

Other areas of the inner brain, including the hippocampus, the amygdala, were similar between the two groups. No differences in the thickness of the outer brain were seen. 

Researchers then divided patients into two groups based on sleep/fatigue problems and gastrointestinal tract dysfunction. Compared to those without these problems, a smaller thalamus was significantly associated with sleep and gastrointestinal disturbances. 

“This is the first study showing an association between higher non-motor symptom burden and thalamic atrophy in PD. Among the non-motor symptoms, sleep/fatigue disturbances and gastrointestinal dysfunction were the non-motor symptoms that drove this correlation,” the researchers wrote.

The team, however, noted that further studies with larger numbers of PD patients are needed to confirm these findings, and use specific scales to measure nighttime and daytime sleep problems and tools that capture gastrointestinal dysfunction.

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Patients’ Self-reported Symptoms Reflect Clinical Assessments of Parkinson’s Severity, Study Finds

Parkinson's, patient-reported symptoms

A patient’s perception of how Parkinson’s disease affects their motor and non-motor skills reflects clinical assessments of disease severity, a study has found.

The findings of the study were presented in the poster, “Modeling the Effect of Patient’s Perception of Non-Motor and Motor Function on Parkinson’s Disease Severity,” during the recent International Congress of Parkinson’s Disease and Movement Disorders, in Nice, France.

In recent years, worldwide regulatory and clinical health authorities have been increasingly interested in evaluating the link between patient-reported outcomes and clinicians’ assessments of Parkinson’s severity.

“Understanding the specific self-reported non-motor and motor functional impairments that contribute to PD [Parkinson’s disease] severity is important to treatment efforts,” the researchers wrote.

These researchers from Rush University set out to determine whether a patient’s perception of how Parkinson’s affected their motor and non-motor skills would match the conclusions of healthcare professionals who assessed disease severity using clinically objective criteria.

To that end, investigators analyzed data from 6,684 patients with Parkinson’s disease that were pooled from the international Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Translation database.

These data contained information from patient-reported impairments in non-motor (Part I) and motor (Part II) categories. These outcomes (assessed in Part I and II) were used to create models of overall disease severity, as objectively measured by healthcare professionals (MDS-UPDRS Part III).

The team created two different models: one focused on patient-reported non-motor outcomes and the other focused on patient-reported motor outcomes. Statistical analyses demonstrated that both models conveyed important information to assess disease severity, as independently measured by examiners in Part III.

In the non-motor model, 10 different categories were found to be important measures of disease severity, including urinary function, cognitive impairment, constipation, hallucinations and psychosis, fatigue, apathy, depressiondaytime sleepiness, pain, and light-headedness.

In the motor model, 13 different categories were considered relevant measures of disease severity, including tremor, walking and balance, getting out of bed, hygiene, handwriting, turning in bed, speech, eating, saliva and drooling, “freezing” of gait, dressing, chewing and swallowing, and hobbies.

The researchers noted that, based on these two models, a patient’s perception of motor function seemed superior to their perception of non-motor function.

“This is an important piece of research coming from a world-renowned group and objectively defines what is now considered the benchmark concept of Parkinson’s disease (PD), that it is effectively as much a non-motor disorder as it is motor, the latter being the traditionally defined concept of this fastest growing neurodegenerative disorder in the world,” K. Ray Chaudhuri, professor of movement disorders and clinical director of the National Parkinson Foundation Centre of Excellence at Kings College in London, said in a news release.

“The researchers were able to show that self-reporting of motor and importantly, non-motor symptoms can successfully be used to construct a severity model of PD,” Chaudhuri added. “This research supports the importance and validity of combining motor and non-motor measurements of PD in terms of grading disease severity as can be done using the MDS-UPDRS.”

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IRL752 May Help Manage Symptoms Unresponsive to L-Dopa, Phase 2 Data Suggests

IRLAB IRL752 dementia

The small molecule IRL752 may be a safe and effective treatment, which could potentially help manage symptoms known to be unresponsive to levodopa, for people with Parkinson’s disease dementia, results from a Phase 2a clinical study suggest.

Preliminary data suggests treatment with IRL752 could reduce apathy, as well as improve executive function and body postural control.

The results were discussed at the 2019 International Congress of Parkinson’s Disease and Movement Disorders, in a poster titled, “A phase IIa trial studying the safety and tolerability of IRL752 in patients with Parkinson’s disease dementia.” The conference is being held Sept. 22-26 in Nice, France.

IRL752 is a small molecule designed by IRLAB Therapeutics that has the ability to enhance communications between nerve cells in the frontal cortex — a major brain area that controls cognitive functions.

In preclinical studies, this new therapeutic candidate was found to increase the availability of two important neurotransmitters — norepinephrine and dopamine — and to modulate nerve cells’ responses and activity. Neurotransmitters are chemical messengers that allow nerve cells to communicate.

Both norepinephrine and dopamine levels are reduced in the frontal cortical brain areas of people with Parkinson’s who also have dementia, previous studies have shown. Scientists hope treatment with IRL752 may counteract these features and help manage cognitive and psychiatric symptoms in this patient population.

The safety and tolerability of IRL752 were first evaluated in 40 healthy volunteers in a placebo-controlled, double-blind Phase 1 trial. Participants were randomly selected to receive single or multiple ascending doses of IRL752 or a placebo, which covered the clinically anticipated dose.

IRL752 was well-tolerated and had a very good safety profile. No serious adverse events were reported during the study.

Supported by these positive results, IRL752’s potential was further explored in a Phase 2a trial (2017-001673-17) conducted in Sweden and Finland.

The study enrolled 32 patients with Parkinson’s disease dementia. Participants were randomly selected to receive either IRL752 or placebo for four weeks in addition to their standard antiparkinsonian medication. The IRL752 dose was adjusted for each patient during the first 14 days, after which dosing was kept stable for an additional 14 days of treatment.

A total 29 of the 32 participants completed the four-week treatment.

Similar to the previous clinical trial, no serious adverse events were reported. In general, all adverse effects were mild in severity and more frequent during the initial titration phase of the trial, when the dose is adjusted until it achieves the desired effect with as few side effects as possible.

Preliminary data on efficacy outcomes suggested that treatment with IRL752 could reduce apathy, as well as improve executive function and body postural control — symptoms known to be unresponsive to levodopa, the gold standard treatment used to manage Parkinson’s.

“These [preliminary] results will be of guidance for the design of further efficacy studies,” the researchers said.

IRLAB Therapeutics also is exploring the potential of another candidate, named IRL790, for the treatment of Parkinson’s-related dyskinesia — involuntary movements that can interfere with normal daily activities. Supported by positive results from a Phase 2 clinical study, the company is now planning a Phase 2b/3 study to be launched in the first half of 2020.

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Low Vitamin D Levels Linked to Added Falls, More Sleep Problems, Depression, Study Shows

low Vitamin D

Low vitamin D levels are associated with a greater tendency for falls, sleep problems, anxiety, and depression in people with Parkinson’s disease, according to a recent study.

The findings, “Relationship between 25‐Hydroxyvitamin D, bone density, and Parkinson’s disease symptoms,” were published in the journal Acta Neurologica Scandinavia.

Vitamin D deficiency and low bone mass are frequently observed in people with Parkinson’s disease (PD). In fact, one particular study found that lack of this vitamin is more common in people with Parkinson’s (55% of patients) than other populations, such as people with Alzheimer’s disease (41% of patients).

But the relationship between vitamin D levels and Parkinson’s has remained controversial. Some studies suggest that taking vitamin D3 — a form of vitamin D used in supplements — can stabilize the disease, while others see no relation with the risk of Parkinson’s.

However, most studies have focused on limited aspects of the disease and did not include important outcomes — notably, non‐motor symptoms.

Vitamin D has a vital role in bone health, since it promotes calcium absorption and bone mineralization, which keeps bones strong and healthy. It also blocks the release of parathyroid hormone (PTH), an hormone that promotes bone tissue reabsorption and bone thinning.

Some studies support that lack of vitamin D results in a greater risk of falls and fractures in Parkinson’s patients, which can increase hospitalization and even fatal disability. Its levels also have been associated with cognition and mood, as well as stomach malfunction, in people with the disease.

While it is possible that deficits in this vitamin impact several symptoms of PD, the connection remains unclear.

To shed light on this relationship, researchers at the Second Affiliated Hospital of Soochow University and Soochow University, in China, set out to determine if vitamin D levels correlated with bone mineral density (BMD) and non‐motor symptoms in Parkinson’s patients.

The team measured blood levels of 25-hydroxyvitamin D, or 25(OH)D — a precursor of the active form of vitamin D and the most accurate indicator of vitamin D levels in the body — and performed extensive clinical evaluations in 182 Parkinson’s patients as well as 185 healthy people (controls).

Participants were recruited from the Second Affiliated Hospital of Soochow University from March 2014 to December 2017.

Bone mineral density — a measure of bone mass and health — was measured at the lumbar spine and the top of the femur (thigh bone) by bone densiometry, which measures bone loss.

The data showed that people with Parkinson’s had significantly lower vitamin D levels in the blood compared with healthy controls — an average of 49.75 versus 43.40 nanomol per liter of 25(OH)D.

In agreement, low levels of vitamin D (below 50 nmol/l) also were more common in Parkinson’s patients (68.68%) than controls (54.05%).

People with lower vitamin D levels were more likely to fall and experience sleep problems, including difficulty in falling asleep (insomnia). They also had significantly more depression and anxiety.

Mean bone densities in both the spine and femur were lower in PD patients, however no correlation was seen between the levels of BMD and vitamin D.

“Together, these results indicate that vitamin D deficiency may play a role in PD pathogenesis [disease manifestations], while vitamin D supplementation may be used to treat the non‐motor symptoms of PD,” the researchers  said.

“As various non-motor symptoms place a burden on individuals with Parkinson’s disease and their caregivers, vitamin D might be a potential add-on therapy for improving these neglected symptoms,” study’s senior author Chun Feng Liu, MD, PhD, said in a press release.

However, the researchers stressed that future studies with a larger sample size are necessary to clarify the role of vitamin D in Parkinson’s disease.

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Parkinson’s Non-Motor Symptoms More Keenly Felt by Care Partners Than Patients, PMD Alliance Survey Finds

non-motor symptoms

An online survey by the nonprofit group PMD Alliance found that care partners are more likely to report Parkinson’s disease-related non-motor symptoms than are patients themselves, and to feel more affected by them.

These responses underscore the need for better recognition and education about Parkinson’s non-motor symptoms, many of which significantly affect quality of life.

A study based on the survey, “Impact of non-motor symptoms in Parkinson’s disease: a PMDAlliance survey,” was published in Neuropsychiatric Disease and Treatment.

Besides its typical motor symptoms, people with Parkinson’s often experience such disease-related issues as cognitive impairment, sleep difficulties, depression, anxiety, and psychosis.

These symptoms affect patients’ quality of life and increase the burden felt by care partners, who play an important role in keeping patients engaged in daily activities.

Care partner, according to the study, refers to a partnership between a care receiver (patient) and giver that’s characterized by mutual cooperation and joint responsibility. It’s distinct from caregiver, which usually implies care provided to people unable to take care for themselves.

To evaluate and better understand the perceptions, experiences, and educational needs of Parkinson’s patients and their care partners in terms of non-motor symptoms, researchers designed a 17-question, patient-oriented survey. The online questionnaire was sent to all members of the PMD Alliance — also known as the Parkinson & Movement Disorder Alliance — most of whom are patients and their care partners. A majority, about 75%, of members are older than 65.

Investigators registered 700 completed surveys. Of these, 378 (54%) came from care partners and 287 (41%) from Parkinson’s patients; the remaining 5% were from “others,” a term that includes health professionals as well as other family members or friends.

“About 90% of the respondents reported having experience with [non-motor symptoms] in [people with Parkinson’s], including sleep problems (84%), cognitive symptoms (76%), anxiety (65%), depression (56%), hallucinations (40%), and delusions (23%),” the researchers wrote.

Compared to patients, care partners were most likely to report these non-motor manifestations, except for sleep problems or excessive tiredness (84% of care partners and 85% of patients).

Overall, non-motor symptoms were reported by more care partners (97%) than by people with the neurodegenerative disorder (80%). Differences in the reported prevalence between care partners (357 respondents) and patients (216) of these symptoms were statistically significant for cognitive challenges (84% vs. 62%), anxiety (69% vs. 57%), depression (59% vs. 50%), hallucinations (51% vs. 23%), and delusions (32% vs. 8%), the researchers state.

Among the 579 respondents with non-motor symptom experience, symptom onset was evident within three years of diagnosis for more than half (53%), and within five years after diagnosis for 72%.

Almost half of all respondents — more care partners than patients — said non-motor manifestations were harder to deal with than motor symptoms.

More care partners than patients also “indicated that [non-motor symptoms] had either ‘very much’ of an impact (28% vs. 7%) or ‘quite a bit’ of an impact (38% vs. 26%) on quality of life,” while patients were more likely (42% vs. 24%) to define these symptoms as having only “‘some’ impact on quality of life,” the researchers wrote.

Daily activities most affected ranged from completing self-care (72%) and making plans or socializing with family and friends (57% and 58%, respectively), to running errands and finishing household chores (both 53%).

Most respondents, especially care partners with or without non-motor symptom experience, expressed an interest in more information and better education regarding cognitive symptoms, sleep problems, anxiety, depression, hallucinations or delusions.

“This survey underscores the significant impact of [non-motor symptoms] on the quality of life of [people with Parkinson’s] and highlights the need for improved recognition and education about its effects,” the researchers concluded.

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TNM Device for Thermal Brain Stimulation Eases Motor and Other Symptoms of Parkinson’s, Small Trial Reports

TNM device study

Twice daily treatment with ThermoNeuroModulation (TNM), a non-invasive device for at-home use, provided sustained motor and non-motor benefits and was associated with high satisfaction in a small group of Parkinson’s patients on standard medications, a clinical trial reports.

The study based on its findings,“Caloric vestibular stimulation for the management of motor and non-motor symptoms in Parkinson’s disease,” was published in the journal Parkinsonism and Related Disorders.

Results of a previous study in a 70-year-old man with Parkinson’s found that daily use of caloric vestibular stimulation (CVS) eased both disease motor and non-motor symptoms by nearly 50%.

CVS, which stimulates the vestibular system, is self-administered via the portable TNM device, delivering thermal waveforms through ear pieces in a headset (37° C–42°C to one ear and 37 °C–17 °C to the other, over about 19 minutes). Ears given the slow warming and cooling waveforms are switched every two days.

The vestibular system is a sensory network with diffuse pathways throughout the brain, and responsible for providing the brain with information about motion, head position, and spatial orientation.

Researchers in the U.K. and U.S. conducted a double-blind and randomized trial (NCT02703844) with 33 Parkinson’s patients to determine whether the TNM device, developed by Scion, could provide sustained and clinically relevant motor and non-motor benefits.

All were on standard anti-parkinsonian therapies, most frequently oral levodopa-based treatments. The median age of the 16 patients undergoing TNM stimulation (10 men, median 10 years since diagnosis) was 68. The remaining 17 patients received a sham (placebo) treatment.

Use of the TNM device for two months followed a four-week baseline period. Participants were further evaluated at five and 24 weeks after treatment. At each visit, the patients were assessed during “on” states – which refer to periods when anti-parkinsonian medications are effective — to judge changes in motor and non-motor symptoms, activities of daily living, and quality of life.

Compared to those on placebo, the 16 patients undergoing TNM showed significantly improved scores in the MDS-UPDRS Part I scale, which refers to non-Motor Aspects of Experiences of Daily Living. “Therapeutic gains for this assessment were greatest 5 weeks after the cessation of treatment although change scores at both time-points surpassed a previously established minimal clinically important difference,” the researchers wrote.

Similar benefits were observed in the Montreal Cognitive Assessment of cognitive impairment, MDS-UPDRS Part II — motor aspects of daily life activities — and Part III (motor exam), the Modified Schwab & England Activities of Daily Living scale, the 10-meter test of walking speed, the Timed Up and Go test of mobility and balance, and the MDS-UPDRS Part IV (motor complications).

Most of these benefits were attributed to lesser dyskinesia, or involuntary and jerky movements, and most levels returned to baseline (those at the study’s start) after six months.

Patients given TNM treatment were unable to correctly guess their study group, which the team partly attributed to difficulty perceiving the gradual improvements.

A total of 34 adverse events (AEs) were reported, 24 in the group undergoing TNM stimulation. The three serious AEs were deemed unrelated to the device. Four AEs — ear discomfort, dizziness/motion sickness and migraine — were considered possibly related to the device, and all resolved after the end of treatment. All other AEs were minor and thought most likely due to the disease.

Most, 25 people, found the device easy to use at home, while six had the opposite opinion but continued its use anyway. All but three found the time spent in treatment as “enjoyable” or “acceptable.” Twelve patients on TNM and 16 on placebo rated their overall experience with the device as “very positive” or “somewhat positive.”

“The results provide evidence that repeated CVS can provide safe and enduring adjuvant relief for motor and non-motor symptoms associated with [Parkinson’s],” the scientists wrote.

“One typically doesn’t see such consistency in study results when evaluating a new therapy,” Hubert Fernandez, director of the Cleveland Clinic’s Neurological Institute, who reviewed the data, said in a press release. “The fact that the gains observed were on top of the standard therapies is quite promising.”

Kallol Ray Chaudhuri, the medical director of the Centre of Excellence in Parkinson’s and Movement Disorders at King’s College, also considered the results “very encouraging.” Chaudhuri added that achieving benefits in non-motor symptoms “would be especially notable.”  Such symptoms, he said, “are often untreated or poorly treated and have a particularly detrimental impact on quality of life, and their treatment is a key unmet need.”

“I am intrigued and want to see where this device technology might go,” Chaudhuri added.

The TNM Device 3.2 was cleared for marketing in the U.S. (ages 12 and older) and the E.U. (adults) for the prevention of episodic migraine. Parkinson’s patients may currently only use the device (TNM Device 4.0) in clinical trials.

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Sleep Deprivation May Amplify Cognitive and Emotional Issues in Parkinson’s, Study Finds

sleep deprivation studied

Not getting enough sleep may cause memory defects and emotional changes in Parkinson’s disease due to changes in dopamine metabolism, according to a study of zebrafish.

The study, “Sleep Deprivation caused a Memory Defects and Emotional Changes in a Rotenone-based Zebrafish Model of Parkinson’s Disease,” was published in Behavioural Brain Research.

Most Parkinson’s patients experience disease-related non-motor symptoms often preceding the onset of hallmark motor signs. Some of Parkinson’s non-motor symptoms include anxiety, apathy, mood changes, cognitive impairment and emotional disorders, which individually or taken together eventually affect patients’ quality of life.

“In addition to cognitive and emotional disorders, sleep abnormalities are also prevalent in [Parkinson’s disease],” the researchers wrote. “The problem of sleep is not only the characteristics of the disease itself, but also related to medication and dyskinesia such as tremor and rigidity.”

Sleep is an essential physiological process, and lack or shortage of sleep time causes fatigue, increase of mood swings, and can affect learning and memory. Some studies have shown that sleep deprivation can result in emotional and cognitive impairments.

Now, a team of Chinese researchers investigated the effects of sleep deprivation on locomotor activity, memory and emotional behavior in a zebrafish model of Parkinson’s disease.

To mimic the neurodegenerative disorder, animals were given rotenone — a pesticide that inhibits function of mitochondria (cells’ powerhouses) — which leads to cellular death and onset of parkinsonian features. People who come in contact with rotenone are at an increased risk of developing Parkinson’s disease.

Zebrafish were deprived of sleep for four weeks by being in an aquarium with around-the-clock lighting. Of note, fish usually are exposed to 10 hours of “lights off” a day. Rotenone-treated and sleep-deprived animals’ results were compared to control animals who were not given rotenone.

Rotenone-treated zebrafish exhibited parkinsonian-like symptoms, particularly slowness of movement. Motor symptoms’ progression was not aggravated by sleep deprivation.

Rotenone treatment alone impaired the zebrafishs’ memories. Compared to control animals, animals treated with rotenone that were sleep deprived had trouble memorizing and discerning similar objects that were presented to them, suggesting sleep deprivation further damages short-term cognitive deficits.

Not getting enough sleep also was found to worsen anxiety and depression-like behavior in the rotenone treated animals.

Scientists then sought to understand if the observed behavioral changes could  be related to the metabolism of dopamine – the chemical messenger that’s in short supply in Parkinson’s disease.

When compared to control animals, those treated with rotenone had lower levels of dopamine in the brain. However, sleep deprivation did not decrease dopamine concentrations any further. DOPAC, the principal metabolite (i.e., product of metabolism) of dopamine, which was reduced after rotenone treatment alone, had its levels restored upon sleep deprivation.

High levels of two types of dopamine receptors (to which dopamine binds), specifically D2 and D3, were observed in rotenone-treated zebrafish, in comparison to the control group. Interestingly, the levels of those same receptors significantly decreased after sleep deprivation.

Dopamine metabolism appears to be altered in rotenone-treated animals and sleep deprivation seems to play a part in such alteration, however there is not a clear understanding as to how this happens yet.

“[Z]ebrafish displayed an anxiety-depressed mood and a decline in memory after [exposure] to Rotenone, and sleep deprivation caused more severe phenotype [disease characteristics] in this model via altering the [dopamine] metabolism and D2 and D3 receptors,” the researchers wrote. “Our studies not only provided the understanding the roles of [sleep deprivation] in PD non-motor dysfunctions, but also provided a useful model for future pathogenesis and therapeutic studies,” they concluded.

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Study Highlights Disparities in Patient and Physician Perceptions Of Parkinson’s

Parkinson's perspectives

A new study highlights some of the differences in perspective on disease management between people living with Parkinson’s disease and doctors treating them.

The study looks at non-motor symptoms, method of medication delivery, and awareness of support services as places where doctors’ and patients’ perceptions don’t line up, and suggests that getting these perceptions in better alignment could help improve treatment outcomes.

Patient and physician perceptions of disease management in Parkinson’s disease: results from a US-based multicenter survey” was published in the journal Neuropsychiatric Disease and Treatment.

The process of treating Parkinson’s disease is complicated and works best when both patients and doctors are on the same page. When there is disconnect, treatment is more likely to be less than optimal, particularly in terms of patients’ quality of life.

To identify such areas of divergence in perspective, researchers developed a questionnaire, which they gave to physicians treating Parkinson’s patients. The physicians’ patients were given a separate questionnaire to complete.

In addition to gathering demographic and health data, the questionnaires included more subjective questions about treatment regimes. For example, both physicians and patients were asked about the effect of Parkinson’s on patients’ quality of life, and both groups were asked about patient satisfaction with medications. There were also questions about what a conversation between a physician and a patient might look like.

The questionnaire was sent to 107 physicians, 70 of whom responded and provided answers regarding 350 different patients. Additionally, 71 patient questionnaires were completed and collected. Of all these, there were 66 patients for whom both physician and patient questionnaires were completed, allowing for the most direct comparison.

There were many areas in which physicians and patients were in agreement. For example, both groups rated the efficacy and safety of a potential treatment as very important in selecting treatments, as would be expected.

Generally, patients and physicians also had similar perceptions on how Parkinson’s was affecting patients’ quality of life, even though physicians reported that this isn’t often formally assessed. The researchers noted that doing such assessments more often might further improve Parkinson’s treatment.

There were also some areas where patients and physicians reported significantly different views.

Patients rated the form of medication delivery (e.g. a pill versus an injection) as more important than physicians in deciding what the best treatment is.

Physicians reported spending more time during patient visits discussing motor symptoms (e.g. tremors, which they felt were most bothersome for most patients) than non-motor symptoms (e.g. depression and anxiety).

In contrast, patients reported a perception of a fairly even split.

“From a physician perspective, there was alignment between the motor symptoms that were most bothersome for patients and those that were most discussed … but disconnect between the most bothersome and most discussed non-motor symptoms (physicians felt fatigue was most bothersome for most patients … [and] cognitive impairment was the most discussed non-motor symptom…),” researchers said.

Finally, physicians tended to view their patients as more knowledgeable about Parkinson’s disease than did the patients themselves. This extended to physicians being much more aware of available support services than the patients.

Nonetheless, this study has numerous limitations, including its sample which, in addition to being small, probably isn’t representative of Parkinson’s patients in terms of age, education, disease status, etc. The study also focused only on patients in the United States, potentially limiting its ability to be generalized.

However, the investigators propose that getting patients and physicians on the same page about these issues could be clinically helpful.

“Non-motor symptoms, form of medication delivery, and awareness of support services are areas where physician and patient alignment could be increased to potentially improve patient outcomes,” they concluded.

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Endurance Exercise May Help Manage Cortisol Levels in Parkinson’s Patients, Study Suggests

cortisol exercise PD

Doing high-intensity endurance exercise reduces morning cortisol levels in patients with Parkinson’s disease, which may have an impact on the progression of non-motor signs and symptoms, a pilot study suggests.

While other studies are needed to confirm if lowering cortisol with physical exercise works for delaying disease worsening, this data supports the further exploration of the role played by the hormone in non-motor symptoms of Parkinson’s.

The study, “Endurance Exercise Reduces Cortisol in Parkinson’s Disease With Mild Cognitive Impairment,” was published in the journal Movement Disorders.

Parkinson’s disease is a complex disorder associated with both motor and non-motor symptoms including sleep problems, depression, and cognitive impairment.

There is evidence that a malfunction of the hypothalamic-pituitary-adrenal axis (HPA) is involved in the progression of non-motor symptoms of Parkinson’s due to an overproduction of the hormone cortisol.

HPA is a system in the body crucial for stress management. It involves a set of complex interactions between two parts of the brain — the hypothalamus and the pituitary glands — and the adrenal glands located at the top of each kidney, which are regulated by different hormones.

After a stressful or threatening event, the HPA axis is activated and several “stress hormones,” primarily cortisol and adrenaline, are released by the adrenal glands into the bloodstream. As the blood levels of cortisol rise, they start to block the release of other hormones from the hypothalamus and the pituitary that, in turn, will induce a drop in cortisol levels.

This type of negative feedback loop is one mechanism by which HPA regulates itself to avoid excessive and sustained production of cortisol.

Beside this natural stress management process, cortisol is also important for a wide range of vital processes, including metabolism and the immune response. There has been a long-standing association between raised or impaired regulation of cortisol levels and a number of psychiatric conditions such as anxiety and depression, even though this is not yet fully understood.

Elevated morning cortisol levels have been reported in Parkinson’s patients. Accordingly, there is evidence that elevated cortisol in Parkinson’s patients is linked to symptoms such as depression and risk behavior.

Physical exercise is associated with a lower production of cortisol in healthy individuals, and there is evidence that it may also reduce the risk and rate of Parkinson’s progression.

Based on this data, the researchers reasoned that doing exercise could lower daytime production of cortisol in Parkinson’s patients, with possible implications for delaying the progression of their non-motor symptoms.

To test this theory, they conducted a small study in which they measured the levels of cortisol in saliva samples collected from eight Parkinson’s patients with mild cognitive impairment (ages 53 to 79). Over six months, participants were asked to perform high-intensity treadmill endurance exercise.

The exercise program included five to 10 minutes of warm-up, 30 minutes of exercise at 80-85% maximum heart rate, followed by five to 10 minutes of cool-down. Participants exercised an average of 2.5 days per week, and over the first eight weeks of training, exercise duration and intensity were gradually increased to target levels.

Saliva samples were collected before and after completing the program, and at specific times immediately after waking up (0, 0.25, 0.50, and 0.75 hours after awakening) and at periods throughout the day (three, six, nine, and 12 hours after awakening).

Overall, cortisol secretion of Parkinson’s patients more closely resembled that of healthy people after they had completed the training program.

Results showed there was an average 19% reduction in cortisol secretion, compared with the pre-training period. In addition, while cortisol reduction was significant during the times immediately after waking up, it was not in the periods later in the day.

“These data support the need for further exploration of HPA axis dysregulation in Parkinson’s disease,” the researchers wrote. “To understand not only its potential role in the mechanisms underlying non-motor symptoms of Parkinson’s, but also its responsiveness to intervention studies such as physical exercise that can improve non-motor symptoms.”

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