Narcolepsy And Parkinson’s Disease

Keyword Evaluation Of Gene Correlates

From the GO analysis of the gene correlates, a functional annotation table was generated for GO Biological Process. Genes associated with keywords were obtained and their frequencies determined. The keyword categories used are as follows: sleep, circadian, Parkinson, locomotion, dopamine, insulin, behavior, learning, memory, and transcription factor 39. Each of the correlates for the genesets are evaluated for keywords related to the phenotypes of narcolepsy, PD, and IR in the hypothalamus, dorsal thalamus, pons, and subcoeruleus nucleus. Most of the keywords of the three sets of gene correlates are associated with subcoeruleus nucleus.

Keyword Enrichment.

Representative keyword enrichment of the gene correlates of LRRK2, HLA-DQB1 and HCRT in the Hypothalamus, Dorsal Thalamus, Pons and Nucleus Subcoeruleus based on GO term classification. LRRK2 gene correlates HLA-DQB1 gene correlates HCRT gene correlates. X-axis, keyword categories Y-axis, frequency of occurrence.

TheLRRK2 gene correlates have the highest frequency of the keyword categories. The highest represented categories are: transcription factor , insulin, behavior, learning, memory, locomotion , dopamine, Parkinson, and sleep and circadian processes .

Daytime Sleepiness And Parkinsons Disease: The Contribution Of The Multiple Sleep Latency Test

1Pós-Graduação em Neuropsiquiatria e Ciências do Comportamento, Universidade Federal de Pernambuco, Recife, PE, Brazil

2Hospital das Clinicas, Universidade Federal de Pernambuco, Recife, PE, Brazil

Academic Editor:

Abstract

Background. Sleep disorders are major nonmotor manifestations of patients with Parkinsons disease , and excessive daytime sleepiness is one of the most common symptoms. Objective. We reviewed a current literature concerning major factors that influence EDS in PD patients, using Multiple Sleep Latency Test . Methods. A Medline search found 23 studies. Results. The presence of EDS was observed in 12.7% to 47% in patients without complaints of daytime sleepiness and 47% to 66.7% with complaints of daytime sleepiness. Despite being recognized by several authors, major factors that influence EDS, such as severity of motor symptoms, use of dopaminergic medications, and associated sleep disturbances, presented contradictory data. . Available data suggest that the variability of the results may be related to the fact that it was conducted with a small sample size, not counting the neuropathological heterogeneity of the disease. Thus, before carrying out longitudinal studies with significant samples, careful analysis should be done by assigning a specific agent on the responsibility of EDS in PD patients.

1. Introduction

2. Materials and Methods

Following data extraction, we selected 23 studies, longitudinal and cross-sectional .

3. Results

4. Discussion

Sleep Disorder Predicts Risk

To establish the strength of the connection between the two conditions, the researchers whose recent findings appear in Brain: A Journal of Neurology worked with 1,280 people with REM sleep behavior disorder across 24 centers of the International RBD Study Group.

The researchers assessed the participants motor function, cognitive abilities, and sensory abilities for a number of years. After a 12-year follow-up period, they found that 73.5 percent of the people involved in this study had developed Parkinsons disease.

Moreover, participants who had started experiencing motor function issues in this period had a threefold increase in the risk of developing Parkinsons disease or related conditions, such as dementia with Lewy bodies.

Also at high risk were participants who had developed cognitive impairment or started experiencing problems with their sense of smell.

These findings confirm that the presence of RBD is, indeed, a strong predictor of Parkinsons disease. All the more so, since the researchers conducted the study in centers across North America, Europe, and Asia, which means that the results apply to diverse populations.

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Researchers Discover Link Between Parkinsons And Narcolepsy

Newswise Parkinson’s disease is well-known for its progression of motor disorders: stiffness, slowness, tremors, difficulties walking and talking. Less well known is that Parkinson’s shares other symptoms with narcolepsy, a sleep disorder characterized by sudden and uncontrollable episodes of deep sleep, severe fatigue and general sleep disorder.

Now a team of UCLA and Veterans Affairs researchers think they know why the two disorders share something in common: Parkinson’s disease patients have severe damage to the same small group of neurons whose loss causes narcolepsy. The findings suggest a different clinical course of treatment for people suffering with Parkinson’s that may ameliorate their sleep symptoms.

More than 1 million people in the U.S. have been diagnosed with Parkinson’s disease, and approximately 20 million worldwide. Narcolepsy affects approximately one in 2,000 individuals about 150,000 in the United States and 3 million worldwide. Its main symptoms are sleep attacks, nighttime sleeplessness and cataplexy, the sudden loss of skeletal muscle tone without loss of consciousness that is, although the person cannot talk or move, they are otherwise in a state of high alertness, feeling, hearing and remembering everything that is going on around them.

Funding for the study was provided by the National Institutes of Health and the Medical Research Service of the U.S. Department of Veterans Affairs.

Parkinsons Sleep Problems: Diagnosis And Treatment

Parkinsons disease is chronic and progressive, meaning it tends to get worse over time. However, there are treatment options that can help manage symptoms and allow patients to get more restful sleep.

The simplest way to start sleeping better with Parkinsons disease is by adopting healthy sleep habits. Sleep hygiene tips for Parkinsons disease sufferers include:

• Sticking to regular bedtimes
• Following a consistent bedtime routine with soothing activities such as listening to music or reading a calming book
• Getting regular exercise, preferably early in the day
• Getting adequate exposure to light, whether outdoors or through light therapy
• Avoiding long naps and naps late in the day
• Creating a cool, dark, and comfortable sleeping environment
• Restricting bedtime activities to sex and sleep only
• Turning off screens an hour before bedtime
• Reducing liquid intake before bedtime
• Avoiding caffeine, alcohol, and tobacco
• Eating a healthy diet and avoiding large meals at night

Light therapy, exercise, and deep brain stimulation have been successfully used to improve overall sleep quality and to treat specific conditions, such as REM sleep behavior disorder, in patients with Parkinsons disease. Cognitive behavioral therapy for insomnia has proven effective at reducing insomnia in healthy adults, although further research is needed on the effects of CBT in patients with Parkinsons disease.

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The Loss Of Orexin Addressing The Underlying Pathology In Narcolepsy Type 1

Orexia is designing orexin receptor agonists and positive modulators that will directly address the underlying disease pathology of Narcolepsy Type 1 by restoring orexin neurotransmission in the brain. This approach may have the potential for greater efficacy, possibly addressing a broader range of NT1 symptoms than current therapies.

Narcolepsy is a chronic neurologic disorder that affects the brains ability to regulate the normal sleep-wake cycle in over 3 million people worldwide. Symptoms usually start between 7-25 years of age, and diagnostic delays of 6-10 years are common. Fifty percent of patients are misdiagnosed at some point during the course of the disease.

Scientific evidence indicates that NT1 is caused by a profound loss of the neurons which produce the neurotransmitter orexin, also called hypocretin. NT1 is characterized by a diverse set of symptoms that include: excessive daytime sleepiness sleep paralysis hallucinations upon waking up or falling asleep disturbed night-time sleep and cataplexy a sudden transient loss of muscle tone that may lead to full body collapse that is usually triggered by strong emotions.

For some individuals with NT1, related symptoms such as insomnia, weight gain, mood fluctuations, and depression can have a significant debilitating impact on their lives, as described in the 2014 FDA Report, Voice of the Patient: Narcolepsy.

Sleep Disorder May Be Early Sign Of Dementia Or Parkinsons Disease

The American Academy of Neurology, an association of more than 21,000 neurologists and neuroscience professionals, is dedicated to improving patient care through education and research. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Parkinsons disease, ALS , dementia, West Nile virus, and ataxia. For more information about the American Academy of Neurology, visit www.aan.com.

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The Treatment Of Sleep Disorders In Parkinsons Disease: From Research To Clinical Practice

• 1Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
• 2Bellaria Hospital, IRCCS Institute of Neurological Sciences of Bologna, Bologna, Italy

Sleep disorders are one of the most frequent non-motor symptoms of Parkinsons disease , usually increasing in frequency over the course of the disease and disability progression. SDs include nocturnal and diurnal manifestations such as insomnia, REM sleep behavior disorder, and excessive daytime sleepiness. The causes of SDs in PD are numerous, including the neurodegeneration process itself, which can disrupt the networks regulating the sleepwake cycle and deplete a large number of cerebral amines possibly playing a role in the initiation and maintenance of sleep. Despite the significant prevalence of SDs in PD patients, few clinical trials on SDs treatment have been conducted. Our aim is to critically review the principal therapeutic options for the most common SDs in PD. The appropriate diagnosis and treatment of SDs in PD can lead to the consolidation of nocturnal sleep, the enhancement of daytime alertness, and the amelioration of the quality of life of the patients.

The Relationship Between Parkinsons Disease And Sleep

Its unclear whether poor sleep causes parkinsonian symptoms to worsen or whether worsening parkinsonian symptoms cause poor sleep. In many cases its likely a case of bidirectionality, with each one exacerbating the other.

Fragmented sleep and sleep deprivation appear to leave the brain more vulnerable to oxidative stress, which has been tied to the development of Parkinsons disease. Parkinsons disease is not usually diagnosed until individuals have developed sufficient motor symptoms, by which time a significant portion of brain cells have already been damaged. If poor sleep quality or having sleep disorders foreshadows the development of parkinsonian symptoms, these could be useful in early diagnosis of the disease.

More research is needed to clarify the multifaceted relationship between Parkinsons disease and sleep. A better understanding of this connection may offer medical experts the unique opportunity to screen at-risk individuals and perhaps delay the onset of the disease.

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Figure 1 Geneset Overlap

A detailed description of all shared genes and their associated function for each brain region is provided in Extended data, Workbook 3 38. Briefly, the dorsal thalamus and subcoeruleus nucleus have the largest number of shared correlates between LRRK2, HCRT, and HLA-DQB1. Many of these genes for both brain regions are associated with neuron, insulin, and dopamine related processes. There are also several genes connected directly to PD. In sharp contrast, however, the dorsal thalamus associated correlates have many genes linked to circadian function.

In the dorsal thalamus, the relevant genes are associated with neuron function , circadian processes , and insulin signaling . Other genes of interest are related to dopamine and also behavior .

In the subcoeruleus nucleus, the relevant genes are also associated with neuron function , insulin signaling , dopamine related processes , and behavior .

There are few shared correlated genes in the hypothalamus and pons. For the hypothalamus, the most pertinent genes are involved in neuron migration and circadian processes. In the pons, the relevant genes are concerned with negative regulation of neuron apoptotic processes, neuron projection, circadian regulation of gene expression, and hippocampus and pyramidal neuron development.

Parkinsons Disease Linked With Narcolepsy

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The onset of Parkinsons Disease is often marked by sleep problems such as Insomnia, nightmares, extreme sleepiness, sleep attacks and REM sleep behavior disorders. These same symptoms are characteristic of Narcolepsy, a disorder caused by the brains inability to regulate sleep/wake cycles normally. A recent study at UCLA finds that PD and Narcolepsy have another common feature: a loss of Orexin /Hypocretin cells in the brain .It was also revealed that the loss of Hcrt cells was correlated with the severity of PD. The results suggest that if the sleep problems caused in PD patients is because of the loss of Hcrt cells, then PD patients may benefit from the treatment of narcolepsy.

Brain Advance Access published online May 9, 2007

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Narcolepsy Drug Has Potential To Help Parkinsons Disease Sleep Problems

FROM JAMA NEUROLOGY

A treatment for narcolepsy reduced sleep problems in individuals with Parkinsons disease who had excessive daytime sleepiness in a double-blind, randomized, placebo-controlled, phase 2a trial.

The trial results provide class I evidence for the efficacy of sodium oxybate in treating sleep-wake disturbances in Parkinsons disease. This finding is based on the extensive, electrophysiologically proven treatment effect that, to our knowledge, is unmatched by any other intervention reported so far, Fabian Büchele, MD, of the department of neurology at University Hospital Zürich and his colleagues wrote in their report .

Sodium oxybaterelated improvements of sleep and EDS correlated significantly, whereas sodium oxybateinduced sleep disturbances predicted insufficient treatment response and AEs , they wrote.

The study of 12 patients used a crossover design to examine how well the sodium oxybate could improve sleep latency and scores on the Epworth Sleepiness Scale. The investigators randomized the patients to receive the central nervous system depressor sodium oxybate followed by placebo, or to placebo first and then the active drug, with a 2- to 4-week washout period in between crossovers. Sodium oxybate or placebo were taken at bedtime, and 2.5-4 hours later, with the dose individually titrated between 3 g and 9 g per night, for 6 weeks.

A Cheaper Quicker Form Of Assessment

Unlike the usual method of assessing the risk of Parkinsons disease, which is called dopamine transporter imaging, the current assessment is inexpensive and easy to apply.

Dopamine transporter imaging, explain Dr. Postuma and colleagues, assesses the integrity of the dopaminergic system, which typically becomes compromised in parkinsonism and Parkinsons disease. However, this test is complex and costly. In contrast, assessing for the risk factors that the current study considers is both quick and cost efficient.

We confirmed a very high risk of in people with REM sleep disorder and found several strong predictors of this progression, notes Dr. Postuma.

As new disease-modifying treatments are being developed for and related diseases, these patients are ideal candidates for neuroprotective trials.

Dr. Ron Postuma

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Methylphenidate And Parkinson’s Disease

Parkinson’s disease is a common disorder caused by the loss of dopamine-producing brain cells. The disorder is generally treated with levodopa combined with carbidopa. Nerve cells use levodopa to make dopamine. Carbidopa delays the conversion of levodopa into dopamine until it reaches the brain. Motor fluctuations are a common, and often difficult to manage, source of disability in people with PD. In this trial researchers will study the effects of methylphenidate , also known as Ritalin-a drug marketed in the U.S. to treat hyperactivity and narcolepsy-on carbidopa/levodopa and other antiparkinson medications taken orally by individuals with Parkinson’s disease who experience motor fluctuations when they take levodopa. The overall goal of this project is to develop better symptomatic therapies for PD. After 2 screening visits to the treatment clinic to evaluate the wearing “on” and “off” effects of levodopa, eligible participants will be scheduled for 3 admissions to the GeneralClinical Research Center at Oregon Health & Science University during which they randomly will receive the study drug, MPD, or placebo, along with their usual carbidopa/levodopa therapy and/or other antiparkinson medications. Also, participants will have their parkinsonism rated and blood pressure and pulse measured at regular intervals. Duration of the study for participants is about 3 weeks and includes 2 outpatient clinic visits and 3 inpatient clinic visits .

Link Between Parkinson’s And Narcolepsy Discovered

Date:

UCLA

Summary:

Parkinson’s disease is well-known for its progression of motor disorders: stiffness, slowness, tremors, difficulties walking and talking. Less well known is that Parkinson’s shares other symptoms with narcolepsy, a sleep disorder characterized by sudden and uncontrollable episodes of deep sleep, severe fatigue and general sleep disorder. Now researchers think they know why — the two disorders share something in common: Parkinson’s disease patients have severe damage to the same small group of neurons whose loss causes narcolepsy.

Parkinson’s disease is well-known for its progression of motor disorders: stiffness, slowness, tremors, difficulties walking and talking. Less well known is that Parkinson’s shares other symptoms with narcolepsy, a sleep disorder characterized by sudden and uncontrollable episodes of deep sleep, severe fatigue and general sleep disorder.

Now a team of UCLA and Veterans Affairs researchers think they know why the two disorders share something in common: Parkinson’s disease patients have severe damage to the same small group of neurons whose loss causes narcolepsy. The findings suggest a different clinical course of treatment for people suffering with Parkinson’s that may ameliorate their sleep symptoms.

In fact, said Siegel, Parkinson’s disease is often preceded and accompanied by daytime sleep attacks, nocturnal insomnia, REM sleep disorder, hallucinations and depression. All of these symptoms are also present in narcolepsy.

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The Pd Narcolepsy And Ir Connection

A protein-protein interaction network revealed the insulin connection between theLRRK2 andHLA-DQB1 networks using the multiple protein option in the STRING database 42. The distribution for the PPI scores for each show that the majority of the interactions fall in the high range with scores between 0.7 and 1.0 . Insulin and its receptor are connected toHLA-DBQ1 through 1st shell interactions both of which are based on crystallographic evidence.INSR is in turn connected toCALM1, a calmodulin binding protein involved in calcium signaling and associated with diverse processes including circadian entrainment . The evidence for theINSR/CALM1 interaction is based on coimmunoprecipitation, electro mobility shift, and western blot assays. Relevant interactions, scores, and references are provided inTable 1.

PPI network linking narcolepsy and Parkinsons through insulin.

PPI network showing the insulin interaction with the Narcolepsy gene and Parkinson’s disease gene Interaction score distribution,X-axis, interaction score Y-axis, frequency.