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What Areas Of The Brain Are Affected By Parkinson’s Disease

Essay About Parkinsons Disease

Parkinson’s Disease: How is the brain affected?

language, called Wernickes aphasia. Cerebral palsy is a broad term for brain damage sustained close to birth that permanently affects motor function. The damage may take place either in the developing fetus, during birth, or just after birth and is the result of the faulty development or breaking down of motor pathways. Cerebral palsy is non-progressive that is, it does not worsen with time. During childhood development, the brain is particularly susceptible to damage because of the rapid growth

Circuit Mechanisms For Dopamine Neuron Vulnerability And Resilience In Parkinsons Disease

Study Rationale: While neurodegeneration in Parkinsons disease affects many cells, dopamine neurons are particularly vulnerable, and their loss drives many of the major motor difficulties in PD. To date, the inner workings of the dopamine neurons themselves have been extensively studied to identify sources for this selective vulnerability. However, neurons in the brain are heavily interconnected and interdependent with their surrounding cells and circuitry. Understanding how the neighborhood in which dopamine neurons live and function influences their well-being is a critical missing piece in the puzzle of PD.

Hypothesis: We hypothesize that circuit properties of incoming neuronal connections , surrounding non-neuronal cells , and key modulatory cells contribute to dopamine neuron loss in PD.

Study Design: We will evaluate circuit contributions to dopamine neuron dysfunction in PD using state-of-the-art mouse genetic models and patient-derived stem cell models . Our team members bring unique, specialized expertise that allows us to isolate and manipulate each of these three components individually to test its role in dopamine neuron degeneration. In addition to functional manipulations, we will capture the molecular signatures of the connections dopamine neurons make with each of its neighbors to determine which are most disrupted in PD.

Leadership
Circuitry and Brain-Body Interactions | 2021

Distributed Circuit Dysfunction Underlying Motor And Sleep Deficits In A Progressive Model Of Parkinsons Disease

Study Rationale: Parkinsons disease begins decades before it compromises the ability to move about in the world and sleep through the night. Understanding how the dysfunction of brain circuits begins and then evolves to cause difficulty in moving and sleeping will allow us to diagnose PD earlierincreasing our chances of halting disease progressionand to better treat the disease once it appears.

Hypothesis: The progressive damage to dopamine-releasing neurons results in staged disruption of neural circuits in larger and larger parts of the brain, ultimately leading to both motor and sleep deficits characteristic of PD.

Study Design: Our plan is to study a new genetically engineered mouse model that manifests a progressive, levodopa-responsive parkinsonism. Importantly, this mouse faithfully reproduces the human staging of pathology in key brain circuits. Using the most advanced methods available for studying and manipulating genetically defined brain circuits, the causal linkage between circuit dysfunction and motor and sleep behavior will be determined.

Impact on Diagnosis: A better understanding of how the circuit dysfunction underlying PD is staged should allow earlier diagnosisenhancing the potential benefit of disease-modifying therapiesand better treatment strategies for later-stage patients.

Leadership
Circuitry and Brain-Body Interactions | 2021

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How Is Parkinsons Disease Diagnosed

Diagnosing Parkinsons disease is sometimes difficult, since early symptoms can mimic other disorders and there are no specific blood or other laboratory tests to diagnose the disease. Imaging tests, such as CT or MRI scans, may be used to rule out other disorders that cause similar symptoms.

To diagnose Parkinsons disease, you will be asked about your medical history and family history of neurologic disorders as well as your current symptoms, medications and possible exposure to toxins. Your doctor will look for signs of tremor and muscle rigidity, watch you walk, check your posture and coordination and look for slowness of movement.

If you think you may have Parkinsons disease, you should probably see a neurologist, preferably a movement disorders-trained neurologist. The treatment decisions made early in the illness can affect the long-term success of the treatment.

Symptoms Of Parkinson’s Disease

What brain areas are affected by Parkinsons?

Parkinsons disease is a progressive disorder and, over time, new symptoms appear and existing symptoms slowly become more severe.2 However, it is not a terminal illness people can live for some 15 to 25 years from the point of diagnosis which makes it a long-term condition.2

of the population over the age of 60 is affected by Parkinson’s disease.6

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Alzheimer’s Stages And Progression

In the early stages of Alzheimers disease and dementia, neurons and their connections are destroyed in the areas of the brain which support memory. In later stages, brain functions involving language, reasoning, and regulating behavior become affected. In most cases, the patient will eventually lose their ability to safely live independently.

In the late stages of Alzheimers, as more neurons are lost, many areas of the brain shrink in size. This process is referred to as widespread brain atrophy, resulting in a significant loss of nerve tissue and severely impaired brain function2.

Activity And Connectivity Drive Neuronal Vulnerability And Disease Progression In Parkinsons Disease

Study Rationale: Specific brain circuits that are highly melanized with age are primarily affected, particularly early, in Parkinsons disease . Models incorporating this aspect of PD have only been developed recently and show that increased neuromelanin production causes neurodegenerative changes consistent with Parkinsons. The regulators of cellular neuromelanin metabolism have not been determined, the effect of neuromelanin on normal activity in these pathways has not been defined, the potential for neuromelanin aggregates to increase alpha-synuclein accumulation has not been evaluated, and the impact of extracellular neuromelanin on detrimental inflammatory processes has not been assessed.

Hypothesis: Activity in melanized brain circuits is a dominant factor in the initiation of PD and sustains its progression by seeding pathology in connected regions and providing the stimulus for chronic inflammation. Manipulating neuromelanin production and/or brain circuit activity can ameliorate these deficits.

Impact on Diagnosis: Diagnosis of neuromelanin changes in the brain are already being assessed for their diagnostic potential, but this study will determine their focus and rate of change with respect to neural activity and clinical features. We will also identify if reducing neuromelanin levels stabilizes pathology and restores brain activity.

Leadership
Circuitry and Brain-Body Interactions | 2021

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Dural Lymphatic Vasculature: A New Player In The Pathophysiology Of Parkinsons Disease

Many researchers are drawn to studying the brain because theyre still making basic discoveries about how this mysterious organ works. One of those recent discoveries may be key to deciphering the causes of Parkinsons disease.

Most organs in the body have a lymphatic system to drain toxins, waste and other unwanted materials. After long believing it did not exist, researchers have realized the brain, too, has a lymphatic system to do this cleansing work.

At Toronto Western Hospital, Scientific Associate Naomi Visanji, a neuroscientist, immediately saw the implications of this discovery. Shes investigating the lymph vessels in the brain to see if they door coulddrain alpha-synuclein, a protein that accumulates in the brain cells critical to Parkinsons disease. That accumulation kills the brain cells producing dopamine, the chemical that signals other cells to initiate movement.

Because lymph vessels are involved in drainage of fluid, waste and other unwanted material, its a natural idea that the vessels might be involved in the drainage of excess toxic proteins in the brain, says Visanji.

Using imaging equipment, Visanji will compare the brains of two mouse models. One has been genetically engineered to remove its lymphatic vessels in the brain the other is a normal mouse.

The next questionrequiring a further studyis whether these vessels are damaged in people with Parkinsons disease.

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What Are The Symptoms

Understanding Parkinson’s disease

Symptoms of PD vary from person to person, as does the rate of progression. A person who has Parkinson’s may experience some of these more common “hallmark” symptoms:

  • Bradykinesia – slowness of movement, impaired dexterity, decreased blinking, drooling, expressionless face.
  • Tremor at rest – involuntary shaking that decreases with purposeful movement. Typically starts on one side of the body, usually the hand.
  • Rigidity – stiffness caused by involuntary increase in muscle tone.
  • Postural instability – sense of imbalance. Patients often compensate by lowering their center of gravity, which results in a stooped posture.

Other symptoms that may or may not occur:

Freezing or being stuck in place Shuffling gait or dragging of one foot Stooped posture Cognitive impairment

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Structural Changes In The Cerebellum

With the deformation-based morphometry method, revealed significant contraction in the left cerebellum in patients with early-stage Parkinsons disease compared with control subjects. Using the voxel-based morphometry method, found that in patients with mild-to-moderate Parkinsons disease with and without resting tremor, grey matter volume is decreased in the right quadrangular lobe and declive of the cerebellum in Parkinsons disease with tremor compared with those without. Other studies also found cognitive- or olfactory-related structural changes in the cerebellum in patients with Parkinsons disease. Therefore, there are specific Parkinsons diseaserelated morphological changes in the cerebellum.

The Effects Of Parkinsons Disease

* Memories: Brain stores short-term memories of the experience in a part of the brain called the hippocampus, then those memories are later consolidated and transferred to another part of the brain, more precisely in neocortex, for a long-term storage Memory cells are placed in three parts of the brain, the hippocampus, the prefrontal cortex, and also the basolateral amygdala, which is responsible of emotional associations. In fact these cells are necessary to evoke the emotions linked with

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What Treatments Are Available

Many Parkinson’s patients enjoy an active lifestyle and a normal life expectancy. Maintaining a healthy lifestyle by eating a balanced diet and staying physically active contributes to overall health and well-being. Parkinson’s disease can be managed with self-care, medication, and surgery.

Self careExercise is as important as medication in the treatment of PD. It helps maintain flexibility and improves balance and range of motion. Patients may want to join a support group and continue enjoyable activities to improve their quality of life. Equally important is the health and well being of the family and caregivers who are also coping with PD. For additional pointers, see Coping With Parkinsons Disease.

These are some practical tips patients can use:

Medications There are several types of medications used to manage Parkinson’s. These medications may be used alone or in combination with each other, depending if your symptoms are mild or advanced.

After a time on medication, patients may notice that each dose wears off before the next dose can be taken or erratic fluctuations in dose effect . Anti-Parkinsons drugs can cause dyskinesia, which are involuntary jerking or swaying movements that typically occur at peak dosage and are caused by an overload of dopamine medication. Sometimes dyskinesia can be more troublesome than the Parkinsons symptoms.

What Are The Treatments

From blood letting to brain stimulation: 200 years of ...

Currently there is no cure for Parkinsons disease.

Symptoms can be mild in the early stages of the condition and people might not need immediate treatment. Your doctor and specialist will monitor your situation.

There are several different types of drugs used to treat Parkinsons disease. Drug treatments are tailored to each individuals needs and are likely to involve a combination of different drugs. Your medication should be reviewed regularly. It is likely that, over time, changes will be made to the types of drugs you take and the doses you take each day.

The main types of drug treatment for Parkinsons disease are:

  • drugs which replace dopamine
  • drugs which mimic the role of dopamine
  • drugs which inhibit the activity of acetylcholine
  • drugs which prevent the body breaking down dopamine
  • other drugs such as anti-sickness medication

Everybody is affected differently by medication. The possible side effects of Parkinsons disease drugs include nausea , vomiting , tiredness and dizziness. Some people might experience confusion, nightmares and hallucinations. For some people, dopamine agonists have been linked to compulsive behaviour such as addictive gambling or hypersexuality .

The effectiveness of the main drug treatment levodopa can wear off over time and its long-term use can cause some people to develop involuntary twisting or writhing movements of the arms, legs or face . To reduce the risk, doctors might delay the use of levodopa for younger people.

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Learn More About Parkinsons Disease

Parkinsons Disease: The Essentials

If youre new to Parkinsons disease and would like a good overview to help you better understand the disease, please view our Parkinsons Disease: The Essentials presentation. Its a great place to get started with reliable and concise information.

Causes

The exact cause of Parkinsons is still unknown, but there is an enormous amount of research being done to learn more. This research has led scientists to formulate a number of theories on the cause of this disease.

Diagnosing

While there is no definitive test that can be taken to determine whether a person has Parkinsons disease, movement disorder specialists look for symptoms and use brain imaging technology to accurately diagnose Parkinsons.

Symptoms

Even though Parkinsons is classified as a movement disorderand its motor symptoms are the most discussed and well-knownthere are many non-motor symptoms that display in people with Parkinsons as well.

Treatments

As of today, there is no cure for Parkinsons disease. But there are many ways in which the disease can be treated to make symptoms more manageable.

Microrna Sequencing Reveals Genetic Pathways

Now, a study in the journal Neurology Genetics suggests that experts could use the expression of certain microRNAs in the cerebrospinal fluid of people with Parkinsons disease not only to follow disease progression but also to determine if a new Parkinsons disease drug works.

MicroRNAs are short sequences of RNA that regulate the expression of mRNAs. The body uses these to translate the genetic code into proteins that the cell needs to function.

The discovery came in a phase 2 trial designed to uncover the mechanism behind a previous finding : that the leukemia drug nilotinib could halt the progression of motor- and non-motor-related symptoms in Parkinsons disease.

The senior author of both papers is Dr. Charbel Moussa, Ph.D., the scientific and clinical research director of the Georgetown University Medical Centers Translational Neurotherapeutics Program in Washington, D.C.

Dr. Moussa told Medical News Today in an interview why his team looked at microRNAs in the cerebrospinal fluid to get a better picture of how the drug was working.

This study shows that you can go to the microRNAs, which are the most stable chemicals in the cerebral spinal fluid, .

And because you can detect microRNAs, then these microRNAs can be benchmarked as biomarkers of disease not only what happens longitudinally in Parkinsons disease, and other new diseases, but also can be used as a marker of drug response.

Dr. Charbel Moussa, Ph.D.

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What Is The Prognosis

The disease gets progressively worse, with people becoming severely disabled within three to five years of onset. Affected individuals are predisposed to serious complications such as pneumonia, choking, head injury, and fractures. The most common cause of death is pneumonia. With good attention to medical and nutritional needs, it is possible for individuals with PSP to live a decade or more after the first symptoms of the disease appear.

Redefining Parkinsons Disease Pathophysiology Mechanisms In The Context Of Heterogeneous Substantia Nigra Neuron Subtypes

Scientists Research the Brain in an Effort to Stop Parkinsonâs Disease

Study Rationale: The motor symptoms of Parkinsons disease result from the degeneration of the dopamine-producing neurons in a brain area called the substantia nigra pars compacta . Recent findings suggest that the SNc is diverse and is comprised of dopamine neurons with distinct properties. How these dopamine neuron subtypes contribute to movement, how they are affected in PD, and how they are modified by deep brain stimulation remains unknown.

Hypothesis: We will determine whether the SNc is comprised of pro-motor and anti-motor dopamine neuron subtypes and selective loss of pro-motor neurons in PD causes an imbalance in dopamine neuron subtypes that underlies the motor symptoms of PD.

Study Design: We will separate these neurons into their distinct genetic subtypes, which will allow us to study their specific physiological, anatomical, and functional properties. We will also determine the molecular and circuit mechanisms underlying the dysfunction of dopamine neurons in a mouse model of PD . Additionally, we will explore whether deep brain stimulation of dopamine neuron inputs contributes to the therapeutic efficacy of this treatment.

Leadership
Circuitry and Brain-Body Interactions | 2021

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Parkinsons Doesnt Always Cause Dementia

While cognitive decline is common in both Alzheimers and Parkinsons, it is less likely to occur in Parkinsons patients. According to studies, only half of those with Parkinsons develop cognitive difficulties. This can range from mild forgetfulness to full-blown dementia.

When dementia does manifest itself with Parkinson, it occurs in the subcortical area of the brain. Alzheimers dementia occurs in the cortical area of the brain. As a result of this, the clinical symptoms of these two dementias can be somewhat different.

Surgical Treatment For Parkinsons

This is advised when the disease progresses and the medications are no longer controlling the symptoms of PD adequately.

  • As the disease progresses, Levodopa still works, but the brains response to the medication becomes less predictable. Levodopa may take longer to kick in and may wear off earlier, requiring patients to take medication more frequently during the day. Higher doses of levodopa are associated with abnormal involuntary movements, known as dyskinesias . Unpredictable medication effect results in OFF time when patients feel stiff, rigid, stuck, frozen, slow, or fatigued, compared to ON time when movements are smooth and closer to normal.
  • Treatment options as the disease progresses include taking levodopa more frequently making the medication last longer by adding medications to reduce the metabolism of levodopa, or dopamine adding or changing to long-acting forms of levodopa , or adding or changing to long-acting forms of dopamine agonist . Amantadine can be added to reduce dyskinesia. As these options are being considered and implemented, its time to consider deep brain stimulation surgery .
  • Deep brain stimulation surgery is FDA-approved for the treatment of motor complications in Parkinsons disease and is not experimental. DBS is not a last-resort treatment. It has been shown that DBS is more beneficial when performed earlier in the course of the disease compared to waiting for disability.

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