PD Terms & Definitions

uh-SEE-tul-KOH-lin-ES-ter-ays A class of drugs used to treat mild to moderate dementia in Parkinson's Disease. These drugs increase brain levels of a neurotransmitter called acetylcholine, which helps neurons communicate with each other and is involved in memory, learning, and thinking.

Rhythmic, involuntary movement of a limb when movement is initiated (for example, when writing or lifting a cup). Not usually seen in the earlier stages of Parkinson's Disease.

Also called tissue-specific stem cells or somatic stem cells, these cells are undifferentiated cells found in various tissues of the adult body, such as bone marrow, blood, skin, and even the brain. Their defining characteristics are: Self-renewal: They can divide and produce more stem cells of the same type. Multipotency: They can differentiate into a limited range of specialized cells, typically related to the tissue they originate from (e.g., blood stem cells make blood cells).

A clumping of proteins inside cell bodies in the brain, which may be toxic. Aggregation of the protein alpha-synuclein is found in Lewy bodies, a pathological hallmark of Parkinson's Disease.

A chemical or drug that turns on or activates a particular part of a cell that regulates disease activity (receptor). For example, dopamine agonists used in the treatment of Parkinson's Disease activate the dopamine receptors in the brain, resulting in improvement in symptoms.

Inability to move ("freezing") or difficulty in initiating or maintaining a body motion. From the Greek a, without, and kinesia, movement.

AL-fuh SIN-yoo-klee-in A protein normally found in neurons, and present in high concentrations in Lewy bodies. A genetic mutation in this protein is the basis for a rare inherited form of Parkinson's Disease.

AL-fuh toh-KOFF-er-ol A biologically active form of vitamin E.

uh-MAN-tuh-deen A drug that improves the symptoms of Parkinson's Disease by increasing the amount of a brain chemical called dopamine. Amantadine can reduce the involuntary movements of Parkinson's Disease by acting on other brain chemicals as well.

Normal animals modified mechanically, genetically or chemically, used to demonstrate all or part of the characteristics of a disease. With models, researchers can study the mechanisms of a disease and test therapies. Also known as preclinical models.

AN-tee-koh-luh-NUR-jik A class of drugs that is often effective in reducing the tremor of Parkinson's Disease. They work by blocking the action of acetylcholine, a neurotransmitter in the brain. However, because acetylcholine is involved in memory, learning, and thinking, anticholinergic drugs can bring about cognitive side effects, including confusion or dementia.

This group of drugs decreases the action of the nerve chemical acetylcholine. These drugs may help reduce rigidity, tremor, and drooling in Parkinson's.

Drugs opposing the actions of the chemical histamine and commonly used to treat allergies. In the past, these drugs were used to treat some of the symptoms of Parkinson's.

A chemical compound or substance that inhibits oxidation, damage to cells' membranes, proteins, or genetic material by free radicals (the same chemical reaction that causes iron to rust). Some studies have linked oxidative damage to Parkinson's Disease.

AN-tee-par-kin-SOH-nee-an Drugs used to treat Parkinson’s Disease and other forms of Parkinsonism, which are neurological conditions that impact movement due to a deficiency of dopamine in the brain. These medications: Increase dopamine levels Mimic dopamine’s effects Prevent dopamine breakdown Balance other brain chemicals involved in movement

AY-poh-MOR-feen A drug used to treat severe Parkinson's Disease. It is a form of morphine that can increase the amount of dopamine available in the brain, thereby decreasing symptoms of Parkinson's.

A new tool, called the a-synuclein seeding amplification assay (aSyn-SAA) can detect pathology in the spinal fluid of individuals who have been diagnosed with Parkinson’s Disease and in individuals who have not yet been diagnosed with the disease, but are a high risk for developing it.

uh-TAK-see-uh Refers to a lack of coordination and balance, and while it's not a core symptom of Parkinson’s Disease (PD), it can appear in certain cases or overlap with PD-like conditions. The word comes from the Greek word meaning “without order.” It describes uncoordinated movement, often due to dysfunction in the cerebellum, the part of the brain responsible for coordination and balance. Symptoms include: Unsteady gait Poor hand-eye coordination Slurred speech Difficulty with fine motor tasks Trouble swallowing or abnormal eye movement

ATH-uh-TOH-sis

A movement disorder sometimes confused with Parkinson's Disease that manifests in low, repetitive, involuntary, writhing movements of the arms, legs, hands, and neck that are often especially severe in the fingers and hands.

Any problem with the functioning of the autonomic nervous system, which controls unconscious body functions that affect the bladder, bowels, sweating, sexual function and blood pressure.

The part of the body's complex system of nerves that controls the involuntary activity of some of the internal organs, such as breathing or heartbeat.

The SCAN (Somato‑Cognitive Action Network) is a brain network that links thinking with movement, and new research shows it plays a central role in Parkinson’s Disease. It is located within the motor cortex, the region responsible for planning and executing body movements. SCAN helps translate cognitive intentions (“I want to move”) into physical actions while also processing feedback from those movements.

The basal ganglia are a group of deep brain structures that play a critical role in Parkinson’s Disease. They are crucial for regulating movement, motor learning, executive functions, and emotional behaviors.

A condition characterized by tremor of the hands, head, voice, and other parts of the body. Essential tremor often runs in families and is sometimes called familial tremor. It is sometimes mistaken for a symptom of Parkinson's Disease.

Drugs that block the action of the hormone epinephrine. Usually used to treat high blood pressure and heart disease, they may be effective in the treatment of benign essential tremor.

Symptoms or treatments that affect both sides of the body or both hemispheres of the brain.

Surgical procedures that target both sides of the brain to manage symptoms affecting both sides of the body. This is typically considered when symptoms have progressed beyond one side and medications are no longer sufficient.

Specific, measurable physical traits used to determine or indicate the effects or progress of a disease or condition. For example, high blood pressure is a biomarker of potential cardiovascular disease. No validated biomarker of Parkinson's Disease currently exists.

BLEF-uh-roh-spaz-um A neurological condition that can occur in people with Parkinson’s Disease (PD), though it is not exclusive to PD. Blepharospasm is a form of focal dystonia, meaning it affects a specific muscle group, in this case, the orbicularis oculi, which controls blinking and eyelid closure. It causes involuntary, repetitive spasms of the eyelids, which can be strong enough to keep the eyes shut for seconds or longer. In PD, blepharospasm may occur intermittently, especially when the eyelids or brows are touched. It can make eye exams difficult, as patients may involuntarily squeeze their eyes shut and struggle to reopen them. It’s often triggered or worsened by: Stress Bright lights Fatigue Eye irritation or dryness

A thin layer of tightly packed cells separating the central nervous system from the body's blood stream. This layer is crucial to protecting the brain from foreign substances, but also blocks some potentially therapeutic treatments from entering the brain via orally administered drugs.

BRAY-dee-kih-NEE-zhuh One of the cardinal clinical features of Parkinson's Disease, the slowing down and loss of spontaneous and voluntary movement. You must have bradykinesia plus at least either tremor or rigidity for a Parkinson's diagnosis to be considered. From the Greek brady, meaning slow, and kinesia, meaning movement.

A drug that is usually given in combination with a Parkinson's drug called levodopa; the combination drug's brand name is Sinemet. Carbidopa improves the effectiveness of levodopa and can be used to reduce its side effects.

A strategy aimed at replacing cells damaged or lost due to disease or injury with healthy new cells. Cell replacement in Parkinson's aims to replace the dopamine-producing cells in the brain that are progressively lost through Parkinson's Disease.

The central nervous system (CNS), which includes the brain and spinal cord, plays a central role in both the development and progression of Parkinson's Disease. The CNS processes sensory information, coordinates movement, and regulates cognition, emotion, and autonomic functions. How Parkinson’s Disease Affects the CNS Dopaminergic Neuron Loss - PD primarily affects the substantia nigra, a region in the midbrain. Neurons in this area produce dopamine, a neurotransmitter crucial for smooth, coordinated movement. As these neurons die, dopamine levels drop, leading to motor symptoms. Lewy Bodies - Abnormal protein clumps called Lewy bodies (made of α-synuclein) accumulate in neurons, disrupting normal cell function and contributing to cell death. Dysfunction in the CNS can also cause non-motor symptoms such as depression and anxiety (due to changes in serotonin and norepinephrine systems) Sleep disturbances (REM behavior disorder) Cognitive impairment and dementia Hallucinations (especially in later stages or with medication)

The part of the brain involved in coordinating movement and balance. It is increasingly recognized as playing a major role in Parkinson’s Disease, both in terms of pathology and compensation. Pathology can include neurodegeneration, α-synuclein pathology (Lewy bodies), and altered cerebellar activity due to abnormal input from the basal ganglia. The cerebellum may also compensate for the loss of dopaminergic function in the basal ganglia. This activity might help preserve motor function in early stages or offset symptoms in later stages.

The outer layer and the largest part of the brain. It is responsible for cognition (thinking, memory, decision-making), sensory perception, voluntary motor control, language, and emotion. As Parkinson's Disease advances, Lewy bodies (abnormal protein aggregates) can spread to the cortex. This contributes to Parkinson’s Disease Dementia (PDD). The cortex works with the basal ganglia to plan and execute movements. In PD, disrupted dopamine signaling affects this loop, leading to: Bradykinesia (slowness) Impaired initiation of movement Mood and behavior changes

kuh-REE-uh A type of involuntary movement disorder characterized by brief, irregular, rapid, dance-like movements that can affect various parts of the body. While chorea is not a hallmark symptom of Parkinson’s Disease (PD), it can occur from high doses of Levodopa and/or long-term Levodopa treatment. The word “chorea” comes from the Greek word for “dance,” reflecting the dance-like, fidgety movements it causes.

KOR-ee-oh-ath-uh-TOE-sis A movement disorder that combines features of both chorea and athetosis. Involving movements, usually of the arms, that are faster than athetosis but slower than chorea, often described as dance-like or fidgety. Although it is not a core symptom of Parkinson’s Disease (PD), it can appear in related conditions or as a side effect of PD treatment, especially levodopa-induced dyskinesia.

Organized medical studies that test the effectiveness of various treatments, such as drugs or surgery, in human beings.

The most common form of Coenzyme Q, a vitamin-like antioxidant. Results of the first placebo-controlled, multicenter clinical trial of the compound, published in October 2002, suggested that it might slow disease progression in patients with early-stage Parkinson's Disease. The results have yet to be confirmed in a larger study.

The mental action or process of acquiring knowledge and understanding through thought, experience, and the senses. Cognition refers to a range of mental processes relating to the acquisition, storage, manipulation, and retrieval of information. It underpins many daily activities, in health and disease, across every age span.

The loss of intellectual functions (such as thinking, remembering, and reasoning) of sufficient severity to interfere with daily functioning. The term cognitive dysfunction includes dementia and executive dysfunction, and may also encompass changes in personality, mood, and behavior. Cognitive dysfunction in Parkinson's Disease typically does not respond to dopamine replacement therapy and ranges from mild impairment to dementia.

A measurable decline in mental abilities such as memory, attention, reasoning, or decision-making compared to an expected baseline for age or health. It can range from mild cognitive impairment (MCI), where changes are noticeable but daily independence is maintained, to severe impairment seen in dementia. To some degree, cognitive impairment affects many people with Parkinson's Disease. The same brain changes that lead to motor symptoms can also result in slowness in memory and thinking. Stress, medication, and depression can also contribute to these changes.

Stiffness in the muscles, with a jerky quality when arms and legs are repeatedly moved.

Irresistible impulses to act, regardless of the rationality of the motivation, or acts performed in response to such impulses. Some compulsive behaviors, such as compulsive gambling, hypersexuality, binge eating and shopping, have been associated with dopamine agonists used to treat Parkinson's Disease, though this association has not been conclusively established.

A drug that blocks an enzyme (catchol-O-methyltransferase) that breaks down dopamine. COMT inhibitors include entacapone and tolcapone. Tolcapone has been known to cause serious liver problems and has been withdrawn from the Canadian and European markets.

Decreased ability of intestinal muscles to move stool through the bowels, often resulting in difficulty moving the bowels or in very hard stools.

KREE-uh-teen A naturally occurring amino acid that helps to supply energy to muscle cells. A preliminary clinical trial in 200 Parkinson's patients, published in February 2006, suggested that creatine may slow the progression of PD and may therefore merit additional study. A much larger study is underway to further evaluate the potential neuroprotective effects of creatine.

KRY-oh-thal-uh-MAH-tuh-mee A surgical procedure where a "super-cooled" probe is inserted deep into the part of the brain called the thalamus in an effort to stop the tremors of Parkinson's Disease. This type of surgery is rarely recommended and has been replaced by deep-brain stimulation (DBS).

CT (Computed Tomography) scan is a technique that uses a series of X-rays to create image "slices" of the body from different orientations to create a two-dimensional cross sectional images of the body. Sometimes called CAT scan, for Cmputed Axial Tomography.

A scan where a drug is injected into the bloodstream to assess dopamine-containing neurons, which are involved in controlling movement. A gamma camera is then used to take pictures of your brain. Analyzing the images can help determine whether the symptoms being experienced are the result of Parkinsonian syndrome. DaTscan is FDA-approved to differentiate between essential tremor and Parkinsonian syndrome. A DaTscan can help a provider differentiate between essential tremor and Parkinson’s, because in essential tremor, there is no loss of dopamine, so the DaTscan image will be normal. A DaTscan cannot, however, help differentiate between some types of atypical Parkinsonism, like Progressive Supranuclear Palsy, Multiple System Atrophy, and Corticobasal Degeneration.

Deep Brain Stimulation (DBS) is a surgical procedure that uses a surgically implanted, battery-operated medical device called a neurostimulator - similar to a heart pacemaker and approximately the size of a stopwatch - to deliver electrical stimulation to targeted areas in the brain that control movement, blocking the abnormal nerve signals that cause tremor and PD symptoms. At present, the procedure is used primarily for patients whose symptoms cannot be satisfactorily controlled with medications.

A decline in memory and/or intellectual functioning severe enough to interfere with social or occupational functioning. Some Parkinson's patients experience dementia, generally at later stages of disease progression. This symptom does not typically respond to dopamine replacement therapy.

A mental state, and non-dopamine-responsive symptom of Parkinson's Disease, characterized by feelings of despondency and a lack of ability to initiate activity.

The study of the process by which organisms grow and develop. Developmental biology studies in Parkinson's Disease hold potential to identify therapeutic targets and new cell replacement strategies.

Identification or naming of a disease by its signs and symptoms.

dis-ee-KWIL-ee-bree-um Unsteadiness or balance problems. A common problem in Parkinson's Disease.

DJ-1, also known as PARK7, is a gene that plays a protective role in cells and mutations. This gene is linked to recessive familial Parkinson’s Disease (PD). DJ-1 contributes to cellular defense against oxidative stress and mitochondrial protection. Mutations in DJ-1 cause early-onset, autosomal recessive PD. These mutations impair the protein’s ability to: Detoxify harmful byproducts of metabolism (like cPGA) Protect mitochondria from oxidative damage Maintain normal cellular function under stress

A chemical produced by the brain; it assists in the effective transmission of messages from one nerve cell to the next. People with Parkinson's Disease have decreased amounts of the chemical in the basal ganglia and substantia nigra, two structures located deep in the brain. Dopamine coordinates the actions of movement, balance, and walking.

A class of drugs commonly prescribed in Parkinson's Disease that bind to dopamine receptors and mimic dopamine's actions in the brain. Dopamine agonists stimulate dopamine receptors and produce dopamine-like effects.

Refers to symptoms of Parkinson's Disease characterized by a lack of improvement when treated with current dopamine-replacement therapies. These symptoms include cognitive dysfunction, postural instability and gait dysfunction, sleep disorders, speech disorders, depression, and others.

DOH-puh-min-UR-jik An adjective used to describe a chemical, a drug, or a drug effect related to dopamine.

Parkinson's symptoms, which have been caused by drugs used to treat other conditions, (for example, Reglan, a drug used to treat stomach problems, and certain antidepressants).

dis-AR-three-uh Slurred or otherwise impaired speech. It is a common problem in Parkinson's Disease, affecting up to 90% of individuals with the condition. It results from weak or slow-moving muscles in the face, mouth, and throat, which are essential for clear and effective speech.

dis-kih-NEE-zhuh Involuntary, uncontrollable, and often excessive movements which are a common side effect of Levodopa treatment for Parkinson's Disease. These movements can be lurching, dance-like, or jerky, and are distinct from the rhythmic tremor commonly associated with Parkinson's Disease. They can include twitches, jerks, twisting, or writhing movements. These involuntary movements can affect various parts of the body, such as the arms, hands, legs, torso, jaw, face, and neck.

dis-FAY-juh Difficulty swallowing. A common problem in Parkinson's Disease that increases the risk of inhaling food or liquids into the airways, which in its later stages can lead to a condition known as "aspiration pneumonia."

Refers to a language disorder that affects the ability to produce or understand spoken language, often involving difficulty with word retrieval, sentence formation, or comprehension. It is typically caused by brain injury, such as stroke, trauma, or neurodegenerative conditions. It is not a primary symptom of PD, but it can occur in some individuals, especially in advanced stages or when there is overlapping pathology (e.g., Alzheimer’s disease or other cognitive decline).

A movement disorder that may be confused with Parkinson's Disease. Dystonia is characterized by abnormal and awkward posture or sustained movements of a hand, foot, or other part of the body; may be accompanied by rigidity and twisting.

Primitive (undifferentiated) cells from the embryo that have the potential to become a wide variety of specialized cell types. Embryonic stem cells are derived from embryos that develop from eggs that have been fertilized in an in vitro fertilization clinic and then donated for research purposes with informed consent of the donors.

en-SEF-uh-LY-tis Encephalitis, which is inflammation of the brain, has a clinical connection to Parkinson’s Disease, particularly through a condition known as post-encephalitic Parkinsonism. The inflammation from encephalitis can damage areas of the brain involved in movement control, especially the basal ganglia and substantia nigra, leading to dopamine deficiency, similar to idiopathic Parkinson’s Disease.

The non-genetic surroundings, conditions or influences that affect an organism. These can be divided into physical, biological, social, cultural, and other factors and may play a role in the onset of various diseases, including Parkinson's Disease. Environmental factors that have been inconclusively linked to Parkinson's Disease risk include exposure to various pesticides and metals.

A type of protein (or sometimes RNA) that acts as a biological catalyst, meaning it speeds up chemical reactions in living organisms without being consumed in the process.

Key Enzymes in Parkinson’s Disease

1. LRRK2 (Leucine-Rich Repeat Kinase 2)
   Function: A kinase enzyme involved in cellular signaling.
   Relevance: Mutations in the LRRK2 gene are one of the most common genetic causes of familial PD.
   Recent Findings: Overactive LRRK2 disrupts communication between dopamine-producing neurons and other brain cells. Inhibiting this enzyme (e.g., with MLi-2) may slow or halt neuron death, offering a promising therapeutic strategy1.
2. MAO-B (Monoamine Oxidase B)
   Function: Breaks down dopamine in the brain.
   Relevance: Overactivity leads to dopamine depletion and increased oxidative stress.
   Treatment: MAO-B inhibitors (e.g., selegiline, rasagiline) are used to prolong dopamine activity in PD patients.
3. COMT (Catechol-O-Methyltransferase)
   Function: Also breaks down dopamine, especially outside the brain.
   Treatment: COMT inhibitors (e.g., entacapone, opicapone) are used alongside levodopa to extend its effectiveness.
4. DJ-1 (PARK7)
   Function: Acts as an antioxidant enzyme and protects cells from oxidative stress.
   Relevance: Mutations in DJ-1 are linked to early-onset PD. It also helps detoxify harmful byproducts of metabolism like cPGA, preventing cellular damage
5. PINK1
   Function: Works with PARKIN to identify and remove damaged mitochondria (mitophagy).
   Relevance: Mutations impair mitochondrial quality control, contributing to neuron degeneration.
6. Tyrosine Hydroxylase
   Function: Converts tyrosine into L-DOPA, the precursor to dopamine.
   Relevance: Reduced activity in PD leads to dopamine deficiency.

ep-ih-dee-mee-OL-uh-jee The study of the patterns, causes, and control of disease in groups of people. Epidemiological studies can be used to better understand potential causes of Parkinson's Disease.

A hormone secreted from the adrenal glands (which sit atop the kidneys) in moments of crisis. It stimulates the heart to beat faster and work harder, increases the flow of blood to the muscles, causes an increased alertness of mind, and produces other changes to prepare the body to meet an emergency. Epinephrine also acts as a chemical messenger in the brain to transmit signals between nerve cells.

A movement disorder that may be confused with Parkinson's Disease. A fast tremor that is most pronounced when performing an action such as writing or bringing a hand to a target - as opposed to the resting tremor of Parkinson's Disease, which is most pronounced when the limb is at rest.

ETH-oh-PRAH-puh-zeen Ethopropazine, also known by brand names like Parsitan or Parsidol, is a phenothiazine-derived medication used in the treatment of Parkinson’s Disease, particularly for managing motor symptoms and drug-induced extrapyramidal side effects. It is no longer widely used for Parkinson’s Disease because newer, more effective medications with fewer side effects have been developed.

ek-SY-tox-ISS-ih-tee Overstimulation of nerve cells by nerve impulses. Excitotoxicity often leads to cell damage or death and may play a role in Parkinson's Disease. In PD, dopaminergic neuron loss disrupts the balance of neurotransmission, leading to excess glutamate activity. This overstimulation of ionotropic glutamate receptors (like NMDA and AMPA receptors) causes: Calcium overload in neurons Oxidative stress Mitochondrial dysfunction Activation of cell death pathways (apoptosis)

Difficulty sustaining "executive functions," higher-order processes that enable us to plan, sequence, initiate, and sustain our behavior toward a given goal, incorporating feedback and making adjustments along the way. Executive functions include aspects of memory, attention, problem solving, and multitasking. Some people with Parkinson's experience executive dysfunction or other forms of cognitive impairment, which do not respond to dopamine replacement therapy.

Physical activity undertaken in order to maintain or improve health. A growing body of evidence suggests that exercise may play an important role in treatment regimens for Parkinson's Disease, and may even slow or stop disease progression. Research is ongoing to understand whether and how exercise confers neuroprotection.

ek-struh-pih-RAM-ih-dul A network of brain structures that play a crucial role in controlling and coordinating movement, and are involved in Parkinson’s Disease. These structures include : Basal ganglia (especially the striatum, globus pallidus, and subthalamic nucleus) Substantia nigra Thalamus Red nucleus Reticular formation In Parkinson’s Disease, the substantia nigra pars compacta, a key part of the extrapyramidal system, degenerates, leading to a dopamine deficiency. This disrupts the balance between dopamine and acetylcholine, impairing the direct and indirect pathways that control movement:

A symptom experienced by some people with Parkinson's Disease, in which there is a reduction in facial expressiveness due to muscle rigidity and bradykinesia (slowness of movement). It’s also known as hypomimia. Facial masking is causd when PD affects the basal ganglia, which controls voluntary muscle movement. As dopamine levels drop, facial muscles become stiff and slow. Common Features of Facial Masking:

• Blank or neutral facial expression
• Reduced blinking
• Difficulty showing emotions (e.g., joy, surprise, sadness)
• Soft or monotone voice (often accompanies hypomimia)
• Social challenges due to the misinterpretation of emotional state

A rare form of Parkinson's Disease that runs in families, in which genetics is believed to play an important role. This form of Parkinson's Disease may account for less than five percent of Parkinson's cases worldwide.

A common, poorly understood symptom of Parkinson's Disease; a state in which one feels tired or exhausted, and the capacity for normal work or activity is reduced.

fes-tih-NAY-shun An involuntary quickening of steps and shuffling after starting to walk. Festination is a common feature of Parkinson's Disease. It is also characterized by a stooped posture, often with the center of gravity leaning forward and difficulty in initiating movement and stopping once started, which can increase the risk of falls. There are two recognized phenotypes of festination: Gait festination – the classic shuffling and accelerating steps. Postural festination – where the forward-leaning posture itself contributes to the need to walk faster to maintain balance.

Refers to the forward bending or curving of body parts, particularly the head, neck, and trunk. This is a common postural abnormality seen in people with Parkinson's Disease and can range from mild stooping to severe deformities.

In Parkinson’s Disease, freezing refers to a sudden, temporary inability to move, most commonly affecting walking. This is known as freezing of gait (FOG) and is one of the more frustrating and potentially dangerous motor symptoms of PD. Key Characteristics of Freezing: Sudden inability to move, often described as feeling like the feet are "glued to the ground." Typically lasts a few seconds to minutes. Most common during walking, especially: Starting to walk Turning Approaching doorways or obstacles Transitioning between surfaces

Parkinsonian gait festination (countable and uncountable, plural festinations) The involuntary shortening of stride and quickening of gait that occurs in some diseases (e.g. Parkinson's Disease). An involuntary quickening of speech in some speech disorders.

Abbreviation for "Glial cell-derived neurotrophic factor." GDNF is part of a family of naturally occurring human growth factors (also known as trophic factors) known to nourish and foster the growth and development of dopamine-generating neurons. Several therapeutic approaches involving GDNF are currently under development.

A novel approach to treat, cure or prevent disease by changing the expression of a person's genes. In Parkinson's Disease, this research primarily seeks to repair or restore the function of dopaminergic neurons in the brain. As of February 2012, several gene therapy trials for Parkinson's Disease are either ongoing or have been completed.

Any inherited genetic pattern that may make some individuals more prone than others to certain health conditions, disorders, or diseases. In relation to Parkinson’s Disease (PD), genetic predisposition refers to an increased likelihood of developing the disease due to inherited genetic mutations or variants. While most cases of PD are sporadic (not inherited), about 10–15% of people with Parkinson’s have a family history of the condition Several genes have been identified that, when mutated, can increase the risk of PD:

• SNCA: Produces alpha-synuclein, a protein that clumps into Lewy bodies in PD brains.
• LRRK2: Mutations here are linked to late-onset PD and are the most common genetic cause.
• PARK2 (parkin), PINK1, and PARK7 (DJ-1): Associated with early-onset PD and typically inherited in a recessive pattern.

• Autosomal dominant: Only one mutated copy of a gene (e.g., SNCA, LRRK2) can cause PD.
• Autosomal recessive: Two mutated copies (e.g., PARK2, PINK1) are needed, often passed silently by parents who don’t show symptoms

The branch of biology that deals with heredity, especially the mechanisms of hereditary transmission via DNA and the variation of inherited characteristics (genes) among similar or related organisms.

An eye disease characterized by damage to the optic nerve, often due to increased intraocular pressure, is a leading cause of irreversible blindness worldwide. Glaucoma is one of the most frequent eye problems reported in people with Parkinson’s Disease, along with dry eye syndrome

GLOH-bus PAL-ih-dus A key structure deep in the brain, located within the basal ganglia, involved in regulating movement, emotion, and cognition. It is divided into two parts:

• Globus Pallidus Externa (GPe)
• Globus Pallidus Interna (GPi)

• Altered GPe activity contributes to motor symptoms like bradykinesia (slowness of movement) and rigidity.
• Recent research shows GPe also plays roles in decision-making and emotional memory, suggesting its involvement in non-motor symptoms of PD such as mood disorders.
• GPi becomes overactive, leading to excessive inhibition of motor areas in the thalamus and cortex, which contributes to movement difficulties.

het-uh-roh-JEE-nee-uh-tee The variable appearance of a condition; the heterogeneity of Parkinson's Disease refers to the fact that its symptoms and appearance vary widely from patient to patient. From the Latin hetero, meaning different, and genus, meaning kind.

hy-po-ki-NEE-zhuh A clinical term for the slow or diminished movement associated with Parkinson's Disease. It is one of the hallmark motor symptoms of PD and is closely related to bradykinesia (slowness of movement) and akinesia (absence of movement). Key Features of Hypokinesia in PD:

• Movements become smaller and less forceful, such as shorter steps or reduced arm swing while walking.
• It can affect facial expressions, leading to a "masked face" appearance.
• Often contributes to micrographia, where handwriting becomes small and cramped.
• May worsen with repetition, known as the sequence effect, e.g., steps or writing becoming progressively smaller

hy-po-MEE-mee-uh A clinical term for the Parkinson's symptom more commonly known as facial masking, an immobile face with reduced blinking. From the Greek hypo, meaning less, and mimia, meaning imitation or expression.

id-ee-oh-PATH-ik An adjective meaning "of unknown cause." The usual form of Parkinson's is idiopathic Parkinson's Disease, where no specific genetic, environmental, or secondary cause can be identified. From Greek roots meaning "a disease of its own kind," in other words, it arises spontaneously or from an unknown origin.

• • IPD accounts for about 85% of all Parkinsonism cases
• It typically begins between the ages of 55 and 65
• Unlike genetic or drug-induced Parkinsonism, idiopathic PD has no identifiable external or hereditary cause.
• Diagnosis is based on clinical symptoms and ruling out other causes through imaging or lab tests.

Any method used to produce a picture of internal body structures. Some imaging techniques commonly used in Parkinson's Disease are: CT (Computed tomography) scan, MRI (Magnetic resonance imaging), and PET (Positron emission tomography) scan

Cells engineered from adult skin cells that share many of the physical, growth and genetic features typically found in embryonic stem cells. First engineered in 2007, these cells can differentiate to produce other tissue types, including what appear at first glance to be cells similar to dopamine neurons (the cells of interest to Parkinson's scientists). While a great deal more research is required, iPS cells are generating excitement in the scientific community because of their potential to achieve the same goals as human embryonic stem cells and therapeutic cloning without engendering political or ethical controversy.

A protective immune response of the body that occurs in reaction to any injury, infection, or harmful stimuli. It involves the immune system releasing chemicals and cells to fight off invaders and start tissue repair. The process typically causes redness, heat, swelling, pain, and sometimes loss of function in the affected area. The reactions produced during inflammation and repair may be harmful or helpful. Work is ongoing to understand the role of inflammation in Parkinson's Disease.

A tremor that occurs when a person attempts voluntary, purposeful, goal-directed movements, such as reaching for a cup or touching their finger to their nose. The tremor typically worsens as the person gets closer to the target. Intention tremor is not typically associated with Parkinson’s Disease. See Resting Tremor and Pill Rolling. Common Causes of Intention Tremor:

• Multiple Sclerosis (MS) – the most frequent cause.
• Cerebellar stroke or injury
• Essential tremor
• Traumatic brain injury
• Certain medications
• Alcohol use disorder

len-TIK-yuh-lur NOO-klee-us A group of nerve cells located in the basal ganglia, which includes the putamen and globus pallidus, is the brain region most affected by Parkinson's Disease. The lenticular nucleus helps regulate voluntary movement, muscle tone, and motor coordination. It receives input from the substantia nigra, which produces dopamine. In PD, the loss of dopamine disrupts this communication, leading to motor symptoms.

An area of cell damage or cell death. Pathological or Accidental Lesions (Secondary Parkinsonism) These are unintentional brain lesions caused by: stroke, trauma, tumors, infections, toxins (e.g., carbon monoxide, manganese), or metabolic disorders. Such lesions can damage areas like the basal ganglia, leading to secondary Parkinsonism, a condition that mimics Parkinson’s Disease but has a different cause and often a different treatment approach. Therapeutic Lesions (Surgical Lesioning) These are intentional, targeted brain lesions created to relieve Parkinson’s symptoms, especially when medications are no longer effective. Types of Surgical Lesioning:

• Thalamotomy: Lesion in the thalamus to reduce tremors.
• Pallidotomy: Lesion in the globus pallidus internus (GPi) to reduce dyskinesias and rigidity.
• Subthalamotomy: Lesion in the subthalamic nucleus (STN) to improve overall motor function1.

• Radiofrequency ablation
• MR-guided focused ultrasound (FUS) – a non-invasive, incisionless method
• Stereotactic radiosurgery

Also called L-dopa, the most commonly administered drug to treat Parkinson's symptoms. Levodopa helps restore levels of dopamine, a chemical messenger in the brain responsible for smooth, coordinated movement and other motor and cognitive functions.

A side effect of taking Levodopa that may occur with prolonged use, marked by abnormal, involuntary movements. Reducing the amount of Levodopa may alleviate the side effect.

Abnormal protein clumps that accumulate in dead or dying dopamine-producing cells of the substantia nigra in Parkinson's Disease. At autopsy, the presence of Lewy bodies is used to confirm a Parkinson's diagnosis.

• Composed mainly of misfolded alpha-synuclein protein.
• Found in areas of the brain responsible for movement, cognition, and emotion.
• Disrupt normal cellular function, leading to cell damage and death.

LIH-vee-do reh-TIK-yuh-lair-iss A purplish or bluish net-like discoloration of the skin that is typically seen below the knee and on the forearm in persons treated with amantadine (such as Symmetrel). This is usually a benign condition.

LRRK2 (Leucine-Rich Repeat Kinase 2) is a gene implicated in up to one percent of Parkinson's Disease cases. It functions as a kinase, an enzyme that modifies the function of proteins. Mutations in LRRK2 are the most common known genetic cause of both inherited and sporadic PD. Function of LRRK2:

• Produces a large, multifunctional protein involved in cell signaling, autophagy, lysosomal function, and inflammatory responses.
• Found in various brain cells, including neurons, astrocytes, and microglia.

• The G2019S mutation is the most frequent pathogenic variant, especially in certain populations (e.g., Ashkenazi Jewish and North African descent).
• This mutation leads to overactive kinase activity, which may contribute to neurodegeneration.

• Astrocytes: LRRK2 affects how enzymes and substances are released, potentially disrupting neuron support systems.
• Microglia: LRRK2 activation can lead to inflammation and the release of toxic substances, especially in response to alpha-synuclein, a protein that forms Lewy bodies.

Abbreviation for "Mesencephalic Astrocyte-derived Neurotrophic Factor." MANF is a trophic factor that is still in the beginning stages of preclinical study. Early data suggests MANF is as effective as GDNF in reducing behavioral deficits in preclinical or animal Parkinson's Disease models. However, there is still a lot of work to do before we can fully assess the potential of MANF to effectively treat Parkinson's in people with the disease.

MY-kroh-ee-LEK-trohdz Thin metallic tubes inserted into the brain and guided by stereotactic methods. They are connected to the operating room computer and used to measure the electrical signal from brain cells during surgical procedures, such as pallidotomy.

my-kroh-GRAF-ee-uh The tendency to have very small handwriting due to difficulty with fine motor movements in Parkinson's Disease. Key Features of Micrographia in PD:

• Handwriting becomes progressively smaller and more difficult to read.
• Often worsens as the person continues writing, known as the sequence effect.
• Reflects underlying bradykinesia (slowness of movement) and hypokinesia (reduced movement amplitude).
• It can be an early sign of Parkinson’s, even before other motor symptoms appear.

• Occupational therapy to improve fine motor skills.
• Use of larger pens, lined paper, or writing guides.
• Medication adjustments to improve motor function.
• Handwriting exercises and cueing techniques (e.g., visual or auditory cues).

Mild cognitive impairment, also known as MCI, ia a decline in memory and/or intellectual functioning that is not as severe as dementia. MCI occurs frequently in Parkinson's Disease and may progress to dementia in some patients.

MY-toh-KON-dree-uhl Mitochondria are the "power plants" of the cell, generating energy needed for cell activity. Reduced or incorrect mitochondrial function has been implicated in oxidative stress that may play a role in Parkinson's Disease.

MON-oh-a-meen OX-ih-dayz Monoamine oxidase inhibitors (MAO) are drugs that enhance the effect of dopamine by preventing enzymes from breaking it down. Some studies suggest that MAO inhibitors may slow the progression of Parkinson's Disease, but this has not been proven in the clinic.

Changes in the ability to move are also referred to as “on-off” times. When Parkinson's medications (Levodopa and dopamine agonists) begin to take effect, the patient experiences periods of good symptom control, called “on” time, when the patient can move and function well.

Conditions including Parkinson's Disease, many neurodegenerative, that prevent normal movement. Some are characterized by lack (or "poverty") of movement, some by excessive movement. Besides Parkinson's, conditions categorized as movement disorders include essential tremor, multiple system atrophy, progressive supranuclear palsy, Huntington's disease, Tourette's syndrome and cerebral palsy.

A neurologist with specific training in the subspecialty of movement disorders. Movement disorders specialists typically follow a greater number of patients with movement disorders, and are thus more experienced in the use of the various medications (and their combinations) as compared to a general neurologist, internist or general practitioner.

A toxic chemical, exposure to which causes Parkinson's Disease symptoms in some intravenous drug users. It is now used to produce Parkinson's symptoms in laboratory animals in order to study the disease.

Abbreviation for "Magnetic Resonance Imaging." MRI is a procedure in which radio waves and a powerful magnet linked to a computer are used to create detailed pictures of areas inside the body. These pictures can show the difference between normal and diseased tissue. MRI makes better images of organs and soft tissue than other scanning techniques, such as CT (computed tomography) scan or x-ray. MRI is especially useful for imaging the brain, spine, the soft tissue of joints, and the inside of bones.

A movement disorder that may be confused with Parkinson's Disease. It is a degenerative condition characterized by low blood pressure when standing. It may lead to parkinsonism, rigidity, ataxia, fainting, or incontinence. Also known as Shy-Drager Syndrome.

MY-oh-kloh-nuhs Jerking, involuntary movement of arms and legs, usually occurring during sleep. These movements can feel like electric shocks and may occur spontaneously or be triggered by movement, sound, or light. While myoclonus is not a core symptom of Parkinson’s Disease (PD), it can occur in some individuals, especially in advanced stages or in atypical Parkinsonian syndromes. It may also appear as a side effect of medications or in Parkinson’s-plus disorders like:

• Multiple system atrophy (MSA)
• Corticobasal degeneration (CBD)
• Progressive supranuclear palsy (PSP)

nee-oh-STRY-uh-tum A vital part of the brain, it is made up of the caudate nucleus and the putamen. These are part of the basal ganglia. These structures are involved in motor control, cognitive processing, and reward-based learning and play a central role in Parkinson's Disease’s motor symptoms and progression.

nyoo-roh-bih-HAY-vyur-uhl Having to do with the way the brain affects emotion, behavior, and learning. Parkinson's Disease can include several neurobehavioral symptoms including depression and anxiety.

nyoo-roh-dee-jen-uh-RAY-shun The slow and progressive death (degeneration) of certain brain systems in conditions such as Parkinson's Disease, Alzheimer's Disease, and Lou Gehrig's Disease (ALS). In Parkinson’s Disease (PD), it refers to the progressive loss of structure and function of neurons, particularly those that produce dopamine in the substantia nigra pars compacta (SNpc), a region of the brain critical for motor control. Consequences:

• Motor symptoms like bradykinesia, rigidity, tremor, and postural instability emerge when 60–80% of dopaminergic neurons are lost
• Non-motor symptoms (e.g., sleep disturbances, mood changes, cognitive decline) may also result from degeneration in other brain regions.

nyoo-roh-LEP-tik (Also called major tranquilizers.) A group of drugs that block dopamine. These medications are used in the treatment of serious psychiatric conditions, but can produce or aggravate symptoms of Parkinson's Disease. These drugs are sold under the brand names Haldol, Compazine, Stelazine, and Thorazine.

A physician specializing in diseases and disorders of the brain, spinal cord, nerves, and muscles, including stroke, Parkinson's Disease, epilepsy, Alzheimer's disease, and muscular dystrophy.

NYOO-ron A nerve cell that is used to transmit information within the central nervous system. Parkinson's Disease involves the death of and/or damage to dopaminergic neurons, those that produce the neurotransmitter dopamine, located in a region of the brain called the substantia nigra.

nyoo-roh-far-muh-KOL-uh-jee Refers to the study and application of drugs that affect the nervous system to manage the symptoms of Parkinson's Disease.

Providing protection to or stimulating the regrowth of any part of the body's nervous system. No currently available treatment for Parkinson's Disease has been proven to provide a neuroprotective or neuroregenerative effect; all available Parkinson's Disease treatments are symptomatic, meaning that they mask the symptoms while the underlying disease continues to progress.

A doctor who operates on the brain and central nervous system.

A specialized chemical messenger (e.g., dopamine, norepinephrine, serotonin) that sends messages from one nerve cell to another. Most neurotransmitters play different roles throughout the body, many of which are not yet known. Key Neurotransmitters in Parkinson’s Disease:

1. Dopamine:
   1. The most critical neurotransmitter affected in Parkinson’s.
   2. Produced by neurons in the substantia nigra.
   3. Responsible for smooth, coordinated muscle movements.
   4. In Parkinson’s, these dopamine-producing neurons degenerate, leading to motor symptoms like tremors, rigidity, and bradykinesia (slowness of movement).
2. GABA (Gamma-Aminobutyric Acid):
   1. An inhibitory neurotransmitter that helps regulate neuronal activity.
   2. In Parkinson’s, the loss of dopamine disrupts the balance between excitatory and inhibitory signals, causing overactivity of GABAergic neurons, which contributes to motor symptoms.
3. Norepinephrine:
   1. A neurotransmitter involved in regulating automatic body functions like blood pressure and heart rate.
   2. Its loss in Parkinson’s may explain non-motor symptoms such as fatigue and blood pressure fluctuations.

NYUR-ter-in A naturally occurring human growth factor (or trophic factor) in the same family as GDNF, known to nourish and foster the growth of dopamine-generating neurons. In of Parkinson’s Disease, neurturin has been studied for its potential to protect and restore dopaminergic neurons. Neurturin has been delivered via gene therapy (e.g., CERE120) in clinical trials. In post-mortem studies of patients who received this therapy, researchers found: • Persistent neurturin expression in the brain even after 10 years. • Increased presence of tyrosine hydroxylase-positive neurons, indicating healthier dopamine-producing cells. • Enhanced signaling activity in treated regions, suggesting long-term bioactivity. • Despite promising results in animal models, human trials have shown limited success, with challenges in achieving widespread and effective delivery of the protein to affected brain areas.

An alkaloid (nitrogen-containing chemical) made by the tobacco plant or produced synthetically that is one of the major chemicals in cigarettes. Epidemiological data have linked cigarette smoking to protection against Parkinson's onset. However, because of the grave health risks associated with smoking, no responsible physician would recommend it as a means of preventing Parkinson's Disease.

Degeneration or destruction of the nerve pathways from the part of the brain called the substantia nigra to the basal ganglia or striatum. These pathways are normally rich in dopamine and are affected in Parkinson's Disease.

Poorly understood symptoms of Parkinson's that affect body systems other than movement. These include cognitive impairment, sleep problems and depression. These typically do not respond to dopamine replacement therapy.

Chemical transmitter found in the brain that plays a significant role in both the motor and non-motor symptoms of Parkinson’s Disease. It is involved in regulating: • Attention and arousal • Mood and anxiety • Sleep-wake cycles • Autonomic functions (like blood pressure and heart rate) It is primarily produced in the locus coeruleus (LC), a small nucleus in the brainstem. It also has anti-inflammatory and antioxidant properties, which may help protect neurons from degeneration.

The NURR1 (Nuclear receptor related 1 protein) gene is a transcription factor belonging to the nuclear receptor family. It regulates the expression of genes essential for the development, survival, and function of dopaminergic neurons in the substantia nigra, the brain region most impacted in Parkinson’s Disease. • NURR1 is vital for the development and long-term survival of dopaminergic neurons. A deficiency or dysfunction in NURR1 can lead to impaired dopamine production and increased vulnerability of these neurons to degeneration. • NURR1 has anti-inflammatory properties. It suppresses the activation of microglia (immune cells in the brain) and the release of pro-inflammatory cytokines. Loss of NURR1 function can lead to chronic neuroinflammation, which contributes to PD progression. • NURR1 influences cellular metabolism, including glucose and lipid metabolism, which are often disrupted in PD. These metabolic changes can affect neuronal energy supply and resilience. Because of its central role in neuron health and inflammation control, NURR1 is being explored as a potential therapeutic target. Enhancing NURR1 activity might help slow or modify disease progression.

A reduced or impaired ability to detect odors, which can be an early sign of Parkinson's Disease. Researchers are studying olfactory dysfunction as a possible avenue toward a biomarker, or molecular fingerprint, of Parkinson's Disease.

Fluctuations that occur in response to levodopa treatment in which the person's mobility changes suddenly and unpredictably from a good response (on) to a poor response (off).

Refers to fluctuations in symptoms that occur in relation to the timing and effectiveness of dopaminergic medications, especially levodopa. • "On" periods: Times when medication is working well, and symptoms like tremors, rigidity, and slowness are well-controlled. Patients can move more freely and function more normally. • "Off" periods: Times when medication effects wear off, and symptoms return or worsen. This can include motor symptoms (e.g., stiffness, tremors, difficulty walking) and non-motor symptoms (e.g., anxiety, fatigue, depression). Causes • Levodopa’s short half-life: As PD progresses, the brain’s ability to store and regulate dopamine declines, making the effects of levodopa more short-lived and unpredictable. • Absorption issues: Factors like delayed gastric emptying or dietary protein can interfere with how well levodopa is absorbed. • Disease progression: The ongoing loss of dopamine-producing neurons contributes to more frequent and severe fluctuations.

A drop in blood pressure during changes in body position (for example, from sitting to standing). Specifically, a drop in systolic blood pressure of ≥20 mmHg or a drop in diastolic blood pressure of ≥10 mmHg within 3 minutes of standing up from a sitting or lying position This can produce dizziness or lightheadedness. Orthostatic Hypotension (OH) is a common and potentially serious non-motor symptom of Parkinson’s Disease (PD), especially in its neurogenic form (nOH). In PD, the autonomic nervous system, which controls involuntary functions like blood pressure regulation, is often impaired. This leads to: • Reduced norepinephrine release from sympathetic nerves • Inability to constrict blood vessels upon standing • Pooling of blood in the legs, reducing blood flow to the brain This form is called neurogenic orthostatic hypotension (nOH) and affects up to 30–50% of people with PD.

A rare speech disorder, which is a symptom of Parkinson's Disease, in which a word or syllable is repeated and the flow of speech is interrupted. In Palilalia • The repetitions often: • Accelerate in speed • Decrease in volume • It typically occurs in spontaneous speech, not in automatic speech like singing or reciting memorized text. • It is not under the speaker’s control, and is more common in advanced stages of PD How It Differs from Other Speech Disorders • Stuttering: Involves repetition of sounds or syllables, often at the beginning of words. Palilalia involves the repetition of whole words or phrases, usually at the end of speech. • Echolalia: Repeating what someone else has said. Palilalia is repeating one’s own speech.

A surgical procedure where the globus pallidus, a structure deep in the brain that is affected by Parkinson's Disease, is removed to improve tremors, rigidity, and bradykinesia. This type of surgery is rarely recommended and has been replaced by deep brain stimulation (DBS).

A surgical procedure in which lesions are produced in the globus pallidus region of the brain in an effort to lessen Parkinson's symptoms such as tremors, rigidity, and bradykinesia. Pallidotomy has become less commonly performed with the establishment of deep brain stimulation (DBS) surgery as a safe and effective surgical intervention for Parkinson's Disease.

Antiquated term for paralysis or an uncontrollable shaking of the body. When he discovered Parkinson's Disease, Dr. James Parkinson named it "the shaking palsy."

The Latin form of the older, popular term "shaking palsy," which was used to designate early Parkinson's diagnosis.

Sensations, usually unpleasant, arising spontaneously in a limb or other part of the body, are experienced as "pins and needles" or fluctuations of warmth or coldness. How Paresthesia Relates to Parkinson’s Disease: • Neurological Basis: Parkinson’s is a neurodegenerative disorder that affects the central nervous system, particularly the dopaminergic neurons in the basal ganglia. This disruption can lead to sensory abnormalities, including paresthesia. • Medication Side Effects: Some medications used to treat PD, such as dopamine agonists or levodopa, may contribute to paresthesia either directly or through interactions with other drugs. • Peripheral Neuropathy: People with PD may also develop peripheral neuropathy, which can cause paresthesia. This may be due to the disease itself or secondary to long-term medication use.

A gene, mutations in which have been associated with a familial form of Parkinson's Disease. How loss of function of parkin leads to dopaminergic cell death is unclear. The current prevailing hypothesis is that the normal function of parkin is to help degrade one or more proteins that are toxic to dopaminergic neurons.

Occur when certain neurons of the brain undergo degeneration. The DaTscan study is primarily designed to differentiate Parkinsonian syndrome from a relatively benign condition called essential tremor.

Generic term referring to slowness and mobility problems that result from or look like Parkinson's Disease. Several conditions that are not actually Parkinson's Disease, including multiple system atrophy and progressive supranuclear palsy, as well as a number of medications, can result in parkinsonism and a misdiagnosis of Parkinson's Disease.

Parkinson's Disease is a chronic, degenerative neurological disorder that affects one in 100 people over age 60. While the average age at onset is 60, people have been diagnosed as young as 18. There is no objective test, or biomarker, for Parkinson's Disease, so the rate of misdiagnosis can be relatively high, especially when the diagnosis is made by a non-specialist. Estimates of the number of people living with the disease therefore vary, but recent research indicates that at least one million people in the United States, and more than five million worldwide, have Parkinson's Disease.

A stoic, mask-like facial expression, with infrequent blinking, is characteristic of Parkinson's Disease. Also known as masked facies or hypomimia. Key Features: • Expressionless Appearance: The face may appear stiff, emotionless, or "stone-like," even when the person is feeling emotions internally. • Muscle Rigidity and Bradykinesia: Parkinson’s affects the muscles of the face, making them rigid and slow to move. This can make it difficult to smile, raise eyebrows, or show other facial expressions. • Impaired Autonomic Movements: Involuntary facial movements like blinking or spontaneous smiling may be reduced. • Communication Challenges: Combined with speech changes (like a soft or monotone voice), masked facies can make it hard for others to interpret the person’s mood or intentions, sometimes leading to misunderstandings.

A database used to record cases of diseases of public health importance. Registries are a valuable epidemiological resource that can be used to calculate and monitor incidence rates and risk, as well as trends in incidence and mortality.

The peripheral nervous system (PNS) is a term referring to the nerves that lie outside of the central nervous system (brain and spinal cord). The PNS connects the central nervous system to organs, limbs, and skin. While Parkinson’s Disease is classically known as a central nervous system (CNS) disorder due to the loss of dopamine-producing neurons in the brain, research shows that the PNS is also involved, especially in early and non-motor symptoms. The PNS includes all the nerves outside the brain and spinal cord, and it’s divided into: • Sensory nerves – carry signals from the body to the brain (e.g., pain, temperature) • Motor nerves – carry signals from the brain to muscles • Autonomic nerves – control involuntary functions (e.g., heart rate, digestion, blood pressure)

PET (Positron Emission Tomography) scan is a procedure in which a small amount of a radioactive drug is injected into a vein, and a scanner is used to make detailed, computerized pictures of areas inside the body where the drug is used. This technique can be used to monitor and produce pictures of metabolic or biochemical activity in the brain. A variety of radioactive drugs are used to produce pictures that provide information about different biological systems.

The use of exercises and physical activities to help condition muscles and restore strength and movement. Similar to exercise, certain forms of physical therapy may be useful to maintain balance and flexibility as part of an overall Parkinson's Disease treatment regimen.

Alternating movements of the thumb and forefinger that give the appearance of rolling a small object between the fingers; a characteristic slow tremor in the fingers of Parkinson's patients.

PINK1 (PTEN-induced putative kinase 1) is a gene of unknown function implicated in rare cases of Parkinson's Disease. It plays a crucial role in mitochondrial health, and its dysfunction is strongly linked to early-onset PD. PINK1 works closely with another protein called PARKIN. When PINK1 detects damaged mitochondria, it recruits and activates PARKIN, which tags the mitochondria for destruction. This process prevents the accumulation of dysfunctional mitochondria, which can be toxic to neurons. In some cases of Parkinson's Disease, mutations in the PINK1 gene impair this quality control system, allowing damaged mitochondria to persist. This leads to: Cellular stress Energy failure Neuronal death, especially in dopamine-producing neurons in the brain These mutations are a known cause of early-onset familial Parkinson’s Disease, often appearing before age 45.

A Parkinson's-like illness, cases of which followed the worldwide flu epidemic of 1918; also called von Economo encephalitis.

Uncontrollable problems with standing or walking, or impaired balance and coordination, which are symptoms of Parkinson's Disease for some patients and do not respond to dopamine replacement therapy.

An involuntary rhythmic shaking that happens when a person holds a body part against gravity, such as extending the arms forward or holding an object like a tray. While resting tremor is the hallmark of Parkinsonian tremor, postural tremors can also occur and become more noticeable as the disease progresses. These tremors are part of a broader category called action tremors, which occur during voluntary movement or when holding a position. In Parkinson’s Disease, postural tremors may coexist with resting tremors and can affect the hands, arms, or other body parts when they are held in a fixed position.

A newer dopamine agonist that is well-tolerated and more effective than its predecessors. As a dopamine agonist, it mimics the action of dopamine, a neurotransmitter that is deficient in people with Parkinson’s. It binds strongly to D2 and D3 dopamine receptors, helping regulate movement, mood, and cognition.

Precursor is used in two primary ways: first, in reference to symptoms, conditions, or biological markers that appear before the classic motor symptoms and may indicate the early or preclinical stages of the disease. These precursors can help in identifying Parkinson’s faster, enabling earlier treatment and potentially slowing disease progression. Some of the most common precursors: 1. REM Sleep Behavior Disorder (RBD) • Acting out dreams due to lack of muscle paralysis during REM sleep. • Up to 70% of people with RBD may develop a neurodegenerative disease like Parkinson’s within 10 years 2. Loss of Smell (Hyposmia) • A diminished sense of smell often occurs years before motor symptoms. • Seen in 75–90% of Parkinson’s patients 3. Depression and Anxiety • These mood disorders may not just be reactions to the disease but part of its biology. • Linked to early loss of dopamine, norepinephrine, and serotonin 4. Constipation • A sign of autonomic nervous system dysfunction, which can precede diagnosis by years 5. Postural Hypotension • Sudden drops in blood pressure when standing, leading to dizziness or fainting Secondly, it can be used to refer to a substance that the body can convert into dopamine to help compensate for the loss of dopamine-producing neurons in the brain. For example, Levodopa is a precursor to dopamine, as it is converted to dopamine in the brain.

The expected course and outcome of a disease, including how symptoms may progress over time, the impact on quality of life, and life expectancy. • Symptom progression: PD is a progressive neurological disorder, meaning symptoms worsen over time. These include motor symptoms (such as tremors, rigidity, and bradykinesia) and non-motor symptoms (like cognitive decline, mood disorders, and sleep irregularities). • Functional decline: As PD advances, individuals may lose independence in daily activities and require assistance or full-time care. • Life expectancy: Most people with PD have a normal or near-normal life expectancy, especially with modern treatments Common factors affecting the prognosis of PD: • Age at diagnosis: Younger individuals often experience slower progression • Type of Parkinson’s: Tremor-dominant types may move more slowly than those with postural instability or gait difficulties • Cognitive function: Early cognitive impairment or Parkinson’s dementia can lead to a poorer prognosis

Progressive Supranuclear Palsy (PSP) is a movement disorder that can be mistaken for Parkinson's Disease. PSP is a degenerative disease of unknown cause characterized by problems looking up and down, frequent falls and parkinsonism. It does not consistently respond to dopamine replacement therapy.

A degenerative brain condition sometimes difficult to distinguish from Parkinson's Disease especially in the early stages. PSP symptoms are rigidity and akinesia (loss of muscle movement), difficulty looking up and down, and speech and balance problems. Those with PSP often have poor response to Parkinson's Disease medications.

A medication used to treat Parkinson's. It is composed of Levodopa and Benserazide. A dopaminergic medication used to treat Parkinson's, it is designed to manage motor symptoms. It contains: • Levodopa: A precursor to dopamine that can cross the blood-brain barrier and is converted into dopamine in the brain, helping to restore movement control. • Benserazide: A peripheral decarboxylase inhibitor that prevents levodopa from being converted into dopamine outside the brain, reducing side effects like nausea and allowing more levodopa to reach the brain.

Disturbance of gait typical of people with symptoms of Parkinson's in which, during walking, steps become faster and faster with progressively shorter steps that passes from a walking to a running pace and may precipitate falling forward.

Process by which cells regulate the expression, localization and degradation of proteins. Mishandling of proteins is of interest to Parkinson's researchers because it has been inconclusively linked to Parkinson's Disease.

Abbreviation for "People with Parkinson's" or "Person with Parkinson's."

The extent that a joint will move from being fully straightened to completely bent.

A once-daily drug that can be taken alone in early Parkinson's Disease or with other medications as the disease progresses. Azilect slows the breakdown of the brain chemical dopamine. Early animal studies suggest Azilect may also slow progression of Parkinson's. Side effects include headache, joint pain, indigestion, and depression.

A structure located on the nerve cell that receives the chemical messenger (neurotransmitter, such as dopamine) sent from an adjacent nerve cell. This is how nerve cells communicate. Most of the drugs used to treat Parkinson's Disease are designed to interact with nerve cell receptors and improve nerve cell communication.

One of the cardinal clinical features of Parkinson's Disease, an unwanted and uncontrollable movement that affects a limb when it is at rest and stops for the duration of a voluntary movement.

A specific type of postural instability where a person tends to fall or step backward involuntarily. It’s a serious motor symptom that significantly increases the risk of falls and injuries. It can occur during standing, walking, or transitioning between positions (e.g., sitting to standing).

Abnormal stiffness in a limb or other body part. while seldom the main symptom early in Parkinson's Disease (PD), is experienced as a stiffness of the arms or legs beyond what would result from normal aging or arthritis. Some people call it “tightness” in their limbs. One of the cardinal clinical features of Parkinson's Disease, rigidity is often most apparent when an examiner moves a patient's limb.

Ribonucleic acid, the chemical responsible for carrying instructions from DNA for the synthesis of proteins, enables various life-enabling functions in body cells. It is a molecule similar to DNA, but it’s typically single-stranded and involved in: • Translating genetic information from DNA into proteins. • Regulating gene expression. • Responding to cellular stress and damage. There are several types of RNA, including: • mRNA (messenger RNA) – carries instructions from DNA to make proteins. • miRNA (microRNA) – regulates gene expression. • siRNA (small interfering RNA) – can silence specific genes. ________________________________________ RNA helps researchers understand which genes are malfunctioning in PD. RNA-based therapies (like siRNA or antisense oligonucleotides) are being explored to: • Silence harmful genes (e.g., those causing alpha-synuclein buildup). • Boost protective genes.

RNA interference (RNAi) is a mechanism in which certain genes in an organism are "silenced" (turned off, so that their normal effects do not occur) by the introduction of small fragments of RNA whose sequence matches that of the gene in question. Researchers can use RNAi to test the functions of genes they are studying, and it may also form the basis of novel therapies to treat disease.

A newer drug used to treat Parkinson's. It works by increasing the amount of dopamine available in the brain. It is sold under the brand name Requip. It can be used alone in early stages or with levodopa in later stages. Common Side Effects: drowsiness, dizziness, nausea, vomiting, hallucinations, confusion, sudden sleep episodes (even during activities like driving), swelling in legs or feet, and increased sweating.

A non-ergoline dopamine agonist, this drug is approved for those with Parkinson's Disease and restless legs syndrome. It comes in the form of a skin patch. Rotigotine binds to dopamine receptors in the brain, by stimulating these receptors, it helps compensate for the loss of dopamine-producing neurons in PD, thereby improving motor symptoms. It also has effects on serotonin (5HT1A) and adrenergic receptors, which may contribute to its broader symptom relief. These are frequently reported and generally mild to moderate side effects include: Nausea and vomiting, drowsiness, dizziness, loss of appetite, difficulty sleeping, increased sweating, headache, skin reactions at the patch site (redness, itching, swelling), vision problems, leg swelling, and uncontrolled, sudden movements. Other, more serious but less common side effects include: sudden sleep attacks during daily activities (e.g., driving), hallucinations or psychotic-like symptoms, sudden drop in blood pressure when standing, fainting, impulse control disorders (e.g., compulsive gambling, shopping, eating, sexual urges), heart rate changes, weight gain and fluid retention, and severe allergic reactions, especially in people sensitive to sulfites. If stopped abruptly or tapered too quickly, withdrawal symptoms may include: fever, severe muscle stiffness, depression, apathy, anxiety, insomnia, sweating, and pain.

Increased oily secretions from the sweat glands of the skin; this occurs often in those with Parkinson's Disease. Presents as red, scaly, oily patches on the skin, dandruff on the scalp, flaking and irritation around the nose, eyebrows, ears, and chest, and sometimes is accompanied by itching or burning. It is not contagious and is often triggered by an overgrowth of Malassezia yeast, excess sebum (skin oil) production, and inflammatory responses. PD affects the nerves that regulate automatic body functions, including those controlling oil glands. This leads to increased sebum production, which feeds yeast and causes inflammation. 30% to 60% of people with Parkinson’s experience seborrheic dermatitis, compared to 3% to 5% in the general population.

A chronic inflammatory skin disorder characterized by: Redness and flaking of the skin Greasy, yellowish scales, especially on the scalp, face (around the nose, eyebrows, and ears), and upper chest Itching or burning sensations It affects about 3–5% of the general population, but 30–60% of people with Parkinson’s experience it.

A drug that slows the breakdown of important brain chemicals like dopamine. This medication may help slow the progression of Parkinson's Disease early in the course of the illness.

A brain neurotransmitter that may be deficient in some cases of depression and whose potential role in Parkinson's Disease is under investigation. New research shows that serotonin signaling changes may occur before dopamine loss, suggesting serotonin could be involved in the earliest stages of PD. Serotonin is linked to sleep disturbances, fatigue, anxiety, and depression, which are all common non-motor symptoms in PD. PD involves not just dopamine loss but also disruption in the balance between dopamine and serotonin. This imbalance affects decision-making, mood regulation, and motivation, particularly in brain regions like the caudate nucleus. Studies using brain imaging and intraoperative recordings show that serotonin responses can distinguish PD from other movement disorders, such as essential tremor.

Old term used for what we now call Parkinson's Disease.

A rare condition where there is failure of the autonomic nervous system and abnormalities in muscle function. A person with Shy-Drager syndrome has symptoms of Parkinson's (Parkinsonism), extremely low blood pressure that worsens upon standing, bladder problems, severe constipation, and decreased sweating.

Drooling.

The brand name of the most commonly prescribed version of the drug levodopa, consisting of a combination of levodopa and carbidopa.

A version of Sinemet that works for a longer period of time as it releases the drug more slowly into the body.

Chronic troubles with the amount, duration or quality of sleep an individual experiences. Some people with Parkinson's experience sleep disorders as a symptom. This symptom typically does not respond to dopamine replacement therapy.

Somatic cell nuclear transfer (SCNT) is a technique in which a nucleus from a patient's body cell, such as a skin cell, is introduced into an unfertilized egg from which the original genetic material has been removed. The egg is then used to produce a blastocyst whose stem cells could be used to create tissue that would be compatible with that of the patient. This is called "therapeutic cloning."

Symptoms that affect up to 90 percent of individuals with Parkinson's Disease at some time in the course of their disease, and that commonly include reduced volume, monopitch, hoarseness, a breathy voice quality and/or imprecise articulation. Parkinson's Disease-associated speech disorders often can be alleviated by a specialized physical therapy regimen.

The most common form of Parkinson's Disease, accounting for upwards of 95 percent of cases, and arising from causes likely to include a combination of genetic and environmental factors. Sporadic Parkinson's Disease is sometimes called idiopathic, meaning that the cause is unknown. Sporadic Parkinson's Disease does not run in families, unlike other (much rarer) forms of Parkinson's Disease.

Stem cells are undifferentiated cells that can develop into many different types of specialized cells. In PD research, scientists aim to transform stem cells into dopamine-producing neurons and transplant them into the brain to restore lost function. Embryonic Stem Cells (ESCs) – These are derived from early-stage embryos and have the flexibility to become any cell type, including neurons. Induced Pluripotent Stem Cells (iPSCs) – These are created by reprogramming adult cells (e.g., skin or blood); therefore, they are genetically matched to the patient, reducing rejection risk. Adult Stem Cells – These are found in tissues such as bone marrow; they have a more limited ability to become different cell types and are less commonly used in PD therapy. There is no FDA-approved stem cell therapy for PD yet. Clinical trials are underway, showing promising safety and early effectiveness. However, challenges include ensuring that cells survive, integrate properly, and don’t cause side effects such as tumors or dyskinesias.

Refers to use of precise coordinates to identify deep structures of the brain. The coordinates may be obtained by fitting a patient's head with a special frame and conducting a CT scan or MRI. The position of the brain structures relative to the frame permits precise, three-dimensional localization of the deep brain structures. Stereotactic techniques are often used for surgical interventions such as DBS and gene therapy.

Surgical technique that involves placing a small electrode in an area of the brain to destroy a tiny amount of brain tissue (see deep brain stimulation).

Striatonigral Degeneration (SND) is a rare neurodegenerative disorder that is closely related to Parkinson’s Disease (PD) but has distinct pathological and clinical features. It is now classified as a subtype of Multiple System Atrophy (MSA-P), the parkinsonian variant of MSA. SND involves progressive degeneration of two key brain regions: the striatum which is involved in motor control and coordination and the substantia nigra which produces dopamine, essential for smooth movement. These areas form the nigrostriatal pathway, which is crucial for regulating movement. Damage to both leads to symptoms similar to Parkinson’s but with some key differences. • SND is not responsive to standard Parkinson’s medications like levodopa, which helps distinguish it clinically. • It often includes autonomic dysfunction (e.g., blood pressure issues, bladder problems) and cerebellar symptoms in some cases. Diagnosis is challenging and often confirmed only through imaging or postmortem pathology.

The largest component of the basal ganglia, the striatum controls movement, balance, and walking. It is sometimes called the corpus striatum. Loss of dopamine in the striatum is responsible for many of the symptoms of Parkinson's Disease.

From the Latin for "black substance," the substantia nigra is a part of the basal ganglia that is rich in dopamine-producing nerve cells and the black pigment neuromelanin. In Parkinson's Disease the loss of nerve cells from this region leads to a dopamine deficit and subsequently to Parkinson's symptoms. While it’s very small, this structure is essential in how your brain controls your body’s movements. It also plays a part in the chemical signaling in your brain, which affects learning, mood, judgment, decision-making and other processes.

Subthalamic nucleus (STN) is a nerve center near the substantia nigra. The STN may be targeted for deep brain stimulation (DBS) to reduce Parkinson's symptoms.

Many people find that support groups are tremendously effective in helping them cope with the day-to-day realities of having Parkinson's Disease. Support groups come in different formats - from large, formal meetings to smaller "living-room" get-togethers - and you may not be equally comfortable or get the same benefit from all. If you don't like the first group you find, look for another that will suit you better. If you can't find any you like in your area, consider starting one. If you are unsatisfied with the available options, it is likely that you're not the only one feeling that way.

Brain surgery that can supplant or supplement drug therapies for Parkinson's Disease in some patients. Deep brain stimulation (DBS) is currently the most common surgery for Parkinson's Disease. Other less frequently performed procedures include surgical lesion of the subthalamic nucleus and of the internal segment of the globus pallidus, a procedure known as pallidotomy. Gene therapy is another approach that involves brain surgery. As in all aspects of their treatment regimen, patients considering surgery should work closely with their individual physicians to assess the risks and potential benefits of surgical intervention.

Tremor that increases when hands are stretched out in front.

The reflexive muscular contraction that causes substances to pass from the mouth through the esophagus and into the body. Some people with advanced Parkinson's Disease develop difficulty swallowing (also called dysphagia), which may become severe enough to require a change in diet.

A drug that releases the nerve chemical messenger dopamine and is useful in treating Parkinson's.

1. Of or pertaining to the symptoms of a disease. 2. A term used by people with Parkinson's to describe the state in which they are strongly affected by the symptoms of their Parkinson's Disease, and in which their medication or treatment regimen is providing little relief. 3. Pertaining to treatments that affect the symptoms of a disease, but not the underlying actions that cause the disease to progress. All currently available treatments for Parkinson's Disease are symptomatic, meaning that they mask symptoms while the disease continues to progress.

Any of a variety of changes in the body or its functions that indicate disease or phases of disease.

This condition is a common side effect of long-term use of medications such as chlorpromazine, Haldol, and Loxapine. People with this condition have the characteristic abnormal, involuntary movements of the face and mouth or arms.

Operation in which a small region of the thalamus (a structure deep in the brain) is destroyed. Tremor and rigidity in Parkinsonism and other conditions may be relieved by thalamotomy. This surgery is rarely recommended and has been replaced by deep brain stimulation.

A large group of brain cells that is centrally placed deep in the brain near its base and serves as a major relay station for impulses traveling from the spinal cord and cerebellum to the cerebral cortex. The thalamus plays a crucial role in Parkinson’s Disease (PD) by acting as a central hub in the brain’s motor and non-motor circuits. While PD is primarily known for the loss of dopamine-producing neurons in the substantia nigra, the thalamus is deeply involved in how those changes affect movement, mood, and cognition.

A toxin is any poisonous substance that can cause harm to cells, tissues, or entire organisms. In the context of Parkinson’s Disease (PD), toxins are important because certain environmental toxins have been linked to the development or acceleration of the disease.

Involuntary, uncontrollable, rhythmic movements (fast or slow) that may affect the hands, head, voice or other body parts. Resting tremor is one of the cardinal clinical features of Parkinson's Disease.

An external or environmental factor such as head trauma, stress or exposure to a toxin that may contribute to the development of a condition or disease.

Trophic factors, also known as neurotrophic factors, are naturally occurring proteins that support the growth, survival, and maintenance of neurons. In the context of Parkinson’s Disease (PD), they are being studied as potential disease-modifying therapies because of their ability to protect and regenerate dopamine-producing neurons in the brain. Key Trophic Factors Studied in PD • GDNF (Glial cell line-derived neurotrophic factor) - Promotes the survival and growth of dopamine neurons. It has been shown to cause neuronal sprouting in animal models. Human trials have had mixed results, partly due to delivery challenges. • Neurturin - Similar to GDNF, with neuroprotective effects • CDNF (Cerebral dopamine neurotrophic factor) and MANF - Newer factors with promising results in animal models. CDNF trial results are pending, but early data suggest motor symptom improvement. • BDNF (Brain-derived neurotrophic factor) and NGF (Nerve growth factor) - Support general neuronal health.

A gene that provides instructions for making an enzyme called ubiquitin carboxyl-terminal esterase L1. This enzyme is found in nerve cells throughout the brain and is probably involved in the cell machinery that breaks down unwanted proteins. In rare familial instances of Parkinson's Disease, mutations in UCH-L1 may increase risk of Parkinson's onset.

Undifferentiated cells taken from umbilical cord blood. These cells can be used in some research toward cell replacement therapies for regenerative medicine and tissue replacement after injury or disease.

Occurring on one side of the body. Parkinson's Disease symptoms usually begin unilaterally.

Surgery performed on one side of the brain.

Various substances found in plants and animals that are required for life-sustaining processes. While anecdotal evidence suggests that taking certain vitamins may prevent or improve some symptoms of Parkinson's Disease, no clinical trial to date has proved this.

Loss of effectiveness of Parkinson's medications between doses. If the effectiveness of a medication does not last until the next dose is due, it "wears off."

The tendency, following long-term levodopa treatment, for each dose of the drug to be effective for shorter periods of time.

A rare form of Parkinson's Disease characterized by onset of symptoms before age 40.