Brain Changes In Parkinson’s Disease

Changes In Cerebellum In Parkinson’s Disease

Increased activity of the cerebellum was observed during cognitive tasks. The cerebellum has reciprocal connections with basal ganglia, and Parkinson’s-related morphological changes were observed in animal models and humans. These changes include significant contraction in the left cerebellum, decrease in the gray matter volume in the right quadrangular lobe. These changes may be induced by degeneration of dopaminergic neurons as the cerebellum receives dopaminergic projections from basal ganglia, and dopaminergic receptors were present in the cerebellum.

Symptoms Of Parkinson Disease

Usually, Parkinson disease begins subtly and progresses gradually.

The first symptom is

• Tremors in about two thirds of people

• Problems with movement or a reduced sense of smell in most of the others

Tremors typically have the following characteristics:

• Are coarse and rhythmic

• Usually occur in one hand while the hand is at rest

• Often involve the hand moving as if it is rolling small objects around

• May be worsened by emotional stress or fatigue

• May eventually progress to the other hand, the arms, and the legs

• May also affect the jaws, tongue, forehead, and eyelids and, to a lesser degree, the voice

In some people, a tremor never develops. Sometimes the tremor becomes less obvious as the disease progresses and muscles become stiffer.

Parkinson disease typically also causes the following symptoms:

Walking becomes difficult, especially taking the first step. Once started, people often shuffle, taking short steps, keeping their arms bent at the waist, and swinging their arms little or not at all. While walking, some people have difficulty stopping or turning. When the disease is advanced, some people suddenly stop walking because they feel as if their feet are glued to the ground . Other people unintentionally and gradually quicken their steps, breaking into a stumbling run to avoid falling. This symptom is called festination.

Parkinson disease also causes other symptoms:

The Parkinson’s Disease Brain: What We Know

Parkinson’s disease is a degenerative disorder of the nervous system, which most scientists agree originates in the brain. We know that Parkinson’s disease causes damage to the nerves in the brain, which in turn reduces dopamine cells, but did you also know that this leads to an accumulation of alpha-synuclein, known more commonly as Lewy bodies? This damage is thought to be what causes the motor symptoms of Parkinson’s disease, though scientists still have many questions as to how this works.

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Tip: Do I Have A Speech Or Voice Problem

These are statements many people have used to describe their voices and the effects of their voices on their lives. Choose the response that indicates how frequently you have the same experience. .

• It is difficult for people to hear me0 1 2 3 4
• People have difficulty understanding me in a noisy room0 1 2 3 4
• My voice difficulties restrict personal and social life0 1 2 3 4
• I feel left out of conversations because of my voice0 1 2 3 4
• My voice problem causes me to lose income0 1 2 3 4
• I feel as though I have to strain to produce voice0 1 2 3 4
• The clarity of my voice is unpredictable0 1 2 3 4
• My voice problem upsets me0 1 2 3 4
• My voice problem makes me feel handicapped0 1 2 3 4
• People ask, Whats wrong with your voice?0 1 2 3 4

To find your score, add up your answers. A score of 10 or higher indicates you might have a speech or voice problem that is affecting your quality of life and you should ask for a referral to a speech pathologist.

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Talk With Others Who Understand

MyParkinsonsTeam is the social network for people with Parkinsons disease. On MyParkinsonsTeam, more than 79,000 members come together to ask questions, give advice, and share their stories with others who understand life with Parkinsons disease.

Are you living with low-volume speech? Share your experience in the comments below, or start a conversation by posting on your Activities page.

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So What Do We Know So Far

Location of the substantia nigra. FrozenManCC BY-SA 4.0

The substantia nigra is an area of the mid brain located at the top of the spinal cord, which has been the focus of much work into how Parkinsons affects the brain.

There are a right and a left substantia nigra, and often one side is affected before the other. Because of this, people with Parkinsons often experience symptoms primarily on one side of their body, particularly in the early stages. Indeed, this common feature of the condition often helps to distinguish Parkinsons from other similar conditions.

When it comes to confirming a diagnosis, it is the substantia nigra where pathologists look for changes at the end of life in brain tissue that has been donated to research. And the loss of the dopamine-producing cells in this area of the brain, accompanied by the presence of clumps of alpha-synuclein protein , has been the hallmark of Parkinsons for decades.

You can read more about the alpha-synuclein protein, and how it plays a role in the spread of Parkinsons, in a previous blog post:

Voice Changes For Early Parkinsons Diagnosis

Researchers at Monash University in Melbourne are studying the vocal cords of people with Parkinsons to determine whether measuring voice changes an early sign of the condition could improve early diagnosis.

As part of the trial, 31 people with different severities of Parkinsons and control participants are being assessed using Computer Tomography scans. The scanner takes 50 snapshots to measure the movement of the vocal cords.

Researchers Dr Andrew Ma and Professor Dominic Thyagarajan hope the use of CT scans will result in Parkinsons diagnoses up to eight years before current clinical diagnoses.

The advantages of this technique are that we get measurable, quantitative data. Its also less invasive for patients compared to laryngoscopy which involves a camera down the throat to look at the vocal cords which had been used in earlier studies. If our technique is proven to be useful, it will be easier to roll out in clinical practice, said Dr. Ma.

Its already been shown in the literature that there are strong links between early Parkinsons and voice, and hopefully we can show that CT scans are able to detect these changes.

Voice changes due to Parkinsons include:

• Dysphonia Where the quality of voice is altered to become breathier and hoarser.
• Hypophonia A soft voice.
• Dysprosody Where the cadence of voice pitch and rhythm changes. Patients may lose ranges of expression or begin speaking in more of a monotone.

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Problems With Speech And Voice

If you experience problems with your speech and voice you may find your speech sounds slurred or unclear, or that you speak more quickly than before. You may also find you have to slow down to make yourself understood. It can also become harder to control how quickly you speak.

Your voice can also change. It may sound:

• unsteady and flat

• difficulty putting enough power into your movements

Speech and language therapists are healthcare professionals who can provide assessment and advice on all aspects of communication, from facial expression and body language to speech and communication aids.

Clinical guidelines recommend that your GP, specialist or Parkinsons nurse should consider referring you to a speech and language therapist with experience of Parkinsons when youre in the early stages of the condition.

This is important because you may not notice changes to your speech and communication if they are subtle. But a speech and language therapist can uncover any issues, help you manage them and stop them becoming worse.

You may find it helpful to have regular check-ups. This will allow your speech and language therapist to monitor whether there are any changes with your speech. If there are, they can recommend specific exercises or programmes to help you.

Another recommendation in the guidelines is that youre given equipment to help you communicate if you need it .

Medication such as levodopa may help improve how loudly and clearly you speak.

Cholinergic Pathology In Parkinson Disease And Parkinsonian Dementia

A key pathologic hallmark of PD is loss of midbrain dopaminergic neurons of the substantia nigra, pars compacta, and of their terminals in the striatum. In addition to the well-known reductions in dopamine, there is convergent evidence for early alterations in cholinergic neurotransmission in PD. Braak et al. note early accumulation of a-synuclein deposition within basal forebrain cholinergic neurons in PD, apparently coincident with the occurrence of Lewy bodies and neuronal loss in the substantia nigra .

2.3.1. Cholinergic forebrain pathology

Significant loss of nbM cholinergic neurons is reported in PD brains . Arendt et al. found greater neuronal loss of nbM neurons in PD compared to AD , suggesting that cholinergic deficits may be at least as prominent in PD as in AD. Dysfunction of the basal forebrain cholinergic system is accompanied by a consistent loss of presynaptic cholinergic markers in cortex, sometimes accompanied by loss of muscarinic receptor binding sites. For example, muscarinic binding and ChAT activity are reduced in the pars compacta of the substantia nigra , hippocampus, and especially in the neocortex in PD .

2.3.2. Cholinergic brainstem pathology

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If I Have Speech And Voice Problems How Can I Maintain And Improve My Communication

Some tips to improve communication include:

• Choose a quiet, low-noise space. Turn off televisions, radios and other devices that create noise.
• Make sure your listener can see your face. Look at the person while you are talking. A well-lit room improves face-to-face conversation, increasing the ability to be understood.
• Use short phrases. Say one or two words or syllables per breath.
• Plan periods of vocal rest before planned conversations or phone calls. Know that fatigue significantly affects your ability to speak. Techniques that work in the morning might not work later in the day.
• Keep your throat hydrated. Drink plenty of water. Dont drink caffeinated or alcoholic beverages. Use a humidifier if the air in your home is dry.
• Keep an upright posture, straight chin, slightly lifted neck to improve airflow from lungs to your vocal cords.
• If you are soft spoken and your voice has become low, consider using an amplifier.

If some people have difficulty understanding you, these additional strategies might help:

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Seeking Help For Cognitive Changes

Cognitive change is a sensitive issue. In fact, the doctor is often as hesitant to address this subject as the person with PD is to ask about it. Sometimes, the doctor will delay discussing cognitive impairment out of concern for the person who is still coping with the shock of a new PD diagnosis or struggling with motor symptoms.

For this reason, the person with PD often needs to be the one to initiate the conversation. Tell your doctor if you or your loved one is experiencing problems that upset the family or cause interruptions at work.

Cognitive issues are never too mild to address with your care team. A doctor can provide ways to help, often referring you to a psychiatrist, neuropsychologist, speech or occupational therapist for further evaluation and assistance. The neuropsychological evaluation can be particularly useful, especially in the early stages of a cognitive problem. Having this baseline test can help the doctor determine whether future changes are related to medications, the progression of the PD itself or to other factors such as depression.

When reporting symptoms of mild cognitive impairment, the doctor will first want to rule out causes other than PD, such as vitamin B-12 deficiency, depression, fatigue or sleep disturbances. It should be noted that PD does not cause sudden changes in mental functioning. If a sudden change occurs, the cause is likely to be something else, such as a medication side-effect.

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Living With Parkinson Disease

These measures can help you live well with Parkinson disease:

• An exercise routine can help keep muscles flexible and mobile. Exercise also releases natural brain chemicals that can improve emotional well-being.
• High protein meals can benefit your brain chemistry
• Physical, occupational, and speech therapy can help your ability to care for yourself and communicate with others
• If you or your family has questions about Parkinson disease, want information about treatment, or need to find support, you can contact the American Parkinson Disease Association.

Enrichment Validation Using Flow Cytometry

Isolated nuclei were analyzed for flow cytometry on a CytoFlex S , and data were analyzed using FlowJo V10. Single nuclei were identified by the presence of DAPI staining in a plot of 405450/45-width signal vs 405450/45-area signal. These nuclei were then analyzed for NeuN expression by looking for A488 fluorescence in the 488525/40 channel. Determination of A488 positivity was made by comparing to a sample stained only with DAPI to define the background. Percent positivity for each sample was defined as the percentage of events in the NeuN-A488+gate, divided by the total number of events identified as Nuclei.

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What Are The Symptoms Of Parkinson Disease

Parkinson disease symptoms usually start out mild, and then progressively get much worse. The first signs are often so subtle that many people don’t seek medical attention at first. These are common symptoms of Parkinson disease:

• Tremors that affect the face and jaw, legs, arms, and hands
• Slow, stiff walking

Where Can You Find Support For Parkinsons

A chronic condition such as Parkinsons can be overwhelming to manage. Its important to have support. Here are some useful resources where you can find educational materials, support groups, and more.

• The Michael J. Fox Foundation: The Michael J. Fox Foundation offers advocacy, educational materials, and community for people with Parkinsons.
• The American Parkinson Disease Association: You can connect with The American Parkinson Disease Association to find wellness programs and other support in your community.
• The Parkinsons Foundation:The Parkinsons Foundation provides online support, a resource library, and connections to local community-based support.
• The Davis Phinney Foundation fro Parkisons: You can learn more about managing Parkinsons through The Davis Phinney Foundation for Parkinsons events, blog, podcasts, webinars, and other resources.

You can read more about early onset Parkinsons by checking out the answers to some common questions below.

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What Are The Symptoms

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

Causes Of Parkinson’s Disease

Parkinson’s disease is caused by a loss of nerve cells in part of the brain called the substantia nigra. This leads to a reduction in a chemical called dopamine in the brain.

Dopamine plays a vital role in regulating the movement of the body. A reduction in dopamine is responsible for many of the symptoms of Parkinson’s disease.

Exactly what causes the loss of nerve cells is unclear. Most experts think that a combination of genetic and environmental factors is responsible.

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Support For People Living With Parkinsons Disease

While the progression of Parkinsons is usually slow, eventually a persons daily routines may be affected. Activities such as working, taking care of a home, and participating in social activities with friends may become challenging. Experiencing these changes can be difficult, but support groups can help people cope. These groups can provide information, advice, and connections to resources for those living with Parkinsons disease, their families, and caregivers. The organizations listed below can help people find local support groups and other resources in their communities.

Sidebar: Advances In Circuitry Research

The brain contains numerous connections among neurons known as neural circuits.

Research on such connections and networks within the brain have advanced rapidly in the past few years. A wide spectrum of tools and techniques can now map connections between neural circuits. Using animal models, scientists have shown how circuits in the brain can be turned on and off. For example, researchers can see correlations between the firing patterns of neurons in a zebrafishs brain and precise behavioral responses such as seeking and capturing food.

Potential opportunities to influence the brains circuitry are starting to emerge. Optogenetics is an experimental technique that involves the delivery of light-sensitive proteins to specific populations of brain cells. Once in place, these light-sensitive proteins can be inhibited or stimulated by exposure to light delivered via fiber optics. Optogenetics has never been used in people, however the success of the approach in animal models demonstrates a proof of principal: A neural network can be precisely targeted.

Thanks in part to the BRAIN Initiative, research on neural circuitry is gaining momentum. The Brain Research through Advancing Innovative Neurotechnologies Initiative is accelerating the development and application of new technologies that enable researchers to produce dynamic pictures of the brain that show how individual brain cells and complex neural circuits interact at the speed of thought.

NIH Publication No. 15-5595

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