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Table of Contents

What is Parkinson’s disease? ........................... 1

What causes the disease?................................. 2

What genes are linked to Parkinson’s disease?...... 4

Who gets Parkinson’s disease?.......................... 6

What are the symptoms of the disease? ............... 8

What other diseases and conditions resemble 

Parkinson’s disease? ....................................14

Parkinsonism resulting from 

neurological disorders..............................18

Environmental causes ..............................20

How is Parkinson’s disease diagnosed? ..............22

What is the prognosis?...................................22

How is the disease treated? .............................23

Drug Therapy ........................................24

Surgery ................................................30

Complementary and Supportive Therapies....33

How can people cope with 

Parkinson’s disease? ....................................35

Can scientists predict or prevent 

Parkinson’s disease? .....................................36

What research is being done? ..........................37

Where can I go for more information? ...............45

Glossary ....................................................48

1

What is Parkinson’s disease?

Parkinson’s disease (PD) is a degenerative disorder 

of the central nervous system that belongs to a 

group of conditions called movement disorders. 

It is both chronic, meaning it persists over a 

long period of time, and progressive, meaning its 

symptoms grow worse over time. As nerve cells 

(neurons) in parts of the brain become impaired 

or die, people may begin to notice problems with 

movement, tremor, stiffness in the limbs or the 

trunk of the body, or impaired balance. As these 

symptoms become more pronounced, people may 

have difficulty walking, talking, or completing 

other simple tasks. Not everyone with one or more 

of these symptoms has PD, as the symptoms appear 

in other diseases as well. 

The precise cause of PD is unknown, although 

some cases of PD are hereditary and can be traced 

to specific genetic mutations. Most cases are 

sporadic—that is, the disease does not typically 

run in families. It is thought that PD likely results 

from a combination of genetic susceptibility and 

exposure to one or more unknown environmental 

factors that trigger the disease. 

PD is the most common form of parkinsonism1

, in 

which disorders of other causes produce features 

and symptoms that closely resemble Parkinson’s 

disease. While most forms of parkinsonism have no 

known cause, there are cases in which the cause is 

known or suspected or where the symptoms result 

from another disorder. 

1 Words in italics appear in a Glossary at the end of this 

information.
2

No cure for PD exists today, but research is ongoing 

and medications or surgery can often provide 

substantial improvement with motor symptoms.

What causes the disease?

Parkinson’s disease occurs when nerve cells, or 

neurons, in the brain die or become impaired. 

Although many brain areas are affected, the most 

common symptoms result from the loss of neurons 

in an area near the base of the brain called the 

substantia nigra. Normally, the neurons in this 

area produce an important brain chemical known 

as dopamine. Dopamine is a chemical messenger 

responsible for transmitting signals between the 

substantia nigra and the next “relay station” of the 

brain, the corpus striatum, to produce smooth, 

purposeful movement. Loss of dopamine results 

in abnormal nerve firing patterns within the brain 

that cause impaired movement. Studies have shown 

that most people with Parkinson’s have lost 60 to 

80 percent or more of the dopamine-producing cells 

in the substantia nigra by the time symptoms appear.

PD does not only affect the brain or the central 

nervous system, but the entire body. In fact, it is 

widely believed that the disease starts in the peripheral 

nervous system, in areas such as the intestine, where 

the nature and features of the disease can be present 

many years before involving the brain. The autonomic 

nervous system, which controls many automatic 

functions such as breathing and movements of the 

intestines, is affected, leading to characteristic signs 

and symptoms ranging from constipation to pain 

to skin changes. While the brain involvement is 
3

responsible for the core 

features, other affected 

locations contribute to the 

complicated picture of PD.

The most common symptoms of PD result 

from the loss of neurons in a part of the 

brain called the substania nigra.

The affected brain cells 

of people with PD contain 

Lewy bodies—deposits of 

the protein alpha-synuclein. 

Researchers do not yet 

know why Lewy bodies 

form or what role they 

play in the disease. Some research suggests that the 

cell’s protein disposal system may fail in people with 

PD, causing proteins to build up to harmful levels 

and trigger cell death. Additional studies have found 

evidence that clumps of protein that develop inside 

brain cells of people with PD may contribute to the 

death of neurons. Some researchers speculate that the 

protein buildup in Lewy bodies is part of an unsuccessful attempt to protect the cell from the toxicity of 

smaller aggregates, or collections, of synuclein. 

Genetics. Scientists have identified several genetic 

mutations associated with PD, including the alphasynuclein gene, and many more genes have been 

tentatively linked to the disorder. Studying the 

genes responsible for inherited cases of PD can help 

researchers understand both inherited and sporadic 

cases. The same genes and proteins that are altered 

in inherited cases may also be altered in sporadic 

cases by environmental toxins or other factors. 

Researchers also hope that discovering genes will 

help identify new ways of treating PD. 

Environment. Exposure to certain toxins has caused 

parkinsonian symptoms in rare circumstances (such 
4

as exposure to MPTP, an illicit drug, or in miners 

exposed to the metal manganese). Other stillunidentified environmental factors may also 

cause PD in genetically susceptible individuals.

Mitochondria. Several lines of research suggest that 

mitochondria may play a role in the development 

of PD. Mitochondria are the energy-producing 

components of the cell and abnormalities in the 

mitochondria are major sources of free radicals—

molecules that damage membranes, proteins, DNA, 

and other parts of the cell. This damage is often 

referred to as oxidative stress. Oxidative stressrelated changes, including free radical damage to 

DNA, proteins, and fats, have been detected in the 

brains of individuals with PD. Some mutations that 

affect mitochondrial function have been identified 

as causes of PD.

While mitochondrial dysfunction, oxidative stress, 

inflammation, toxins, and many other cellular 

processes may contribute to PD, the actual cause 

of the cell loss death in PD is still undetermined. 

What genes are linked to Parkinson’s disease?

Several genes have been definitively linked to PD. 

The first to be identified was alpha-synuclein. In the 

1990s, researchers at National Institutes of Health 

and other institutions studied the genetic profiles of 

a large Italian family and three Greek families with 

familial PD and found that their disease was related 

to a mutation in this gene. They found a second 

alpha-synuclein mutation in a German family with 

PD. These findings prompted studies of the role of 
5

alpha-synuclein in PD, which led to the discovery 

that Lewy bodies seen in all cases of PD contain 

alpha-synuclein protein. This discovery revealed 

the link between hereditary and sporadic forms of 

the disease.

Some research suggests that mitochondria (shown above), the energy-producing 

components of a cell, may play a role in PD development.

In 2003, researchers studying inherited PD 

discovered that the disease in one large family 

was caused by a triplication of the normal alphasynuclein gene on one copy of chromosome 4 (a 

chromosome is a threadlike structure of a protein 

and the genetic material DNA). This triplication 

caused people in the affected family to produce 

too much of the normal alpha-synuclein. This 

study showed that an excess of the normal form of 

synuclein could result in PD, just as the abnormal 

form does. 

Other genes linked to PD include parkin, DJ1, PINK1, and LRRK2. DJ-1 and PINK1 cause 

rare, early-onset forms of PD. The parkin gene is 

translated into a protein that normally helps cells 

break down and recycle proteins. DJ-1 normally 
6

helps regulate gene activity and protect cells from 

oxidative stress. PINK1 codes for a protein active 

in mitochondria. Mutations in this gene appear to 

increase susceptibility to cellular stress. 

Mutations in LRRK2 were originally identified in 

several English and Basque families as a cause of a 

late-onset PD. Subsequent studies have identified 

mutations of this gene in other families with PD as 

well as in a small percentage of people with apparently 

sporadic PD. LRRK2 mutations are a major cause 

of PD in North Africa and the Middle East.

Another interesting association is with the GBA 

gene, which makes the enzyme glucocerebrosidase. 

Mutations in both GBA genes cause Gaucher disease 

(in which fatty acids, oils, waxes, and steroids 

accumulate in the brain), but different changes in 

this gene are associated with an increased risk for 

Parkinson’s disease as well. Investigators seek to 

understand what this association can tell us about 

PD risk factors and potential treatments.

Who gets Parkinson’s disease?

Estimates suggest that about 50,000 Americans 

are diagnosed with PD each year, although some 

estimates are much higher. Getting an accurate 

count of the number of cases is difficult because 

many people in the early stages of the disease may 

assume their symptoms are the result of normal 

aging and do not seek medical attention. Diagnosis 

is sometimes complicated by the fact that other 

conditions may produce symptoms of PD and 

there is no definitive test for the disease. 
7

People with PD may sometimes be told by their 

doctors that they have other disorders, and people 

with PD-like diseases may be incorrectly diagnosed 

as having PD. 

PD affects about 50 percent more men than women, 

and the reasons for this discrepancy are unclear. 

While PD occurs in people throughout the world, a 

number of studies have found a higher incidence in 

developed countries. Other studies have found an 

increased risk in people who live in rural areas with 

increased pesticide use. However, those apparent 

risks are not fully characterized. 

One clear risk factor for PD is age. The average 

age of onset is 60 years, and the incidence rises 

significantly with advancing age. However, about 

5 to 10 percent of people with PD have “early-onset” 

disease that begins before the age of 50. Some earlyonset cases are linked to specific gene mutations 

such as parkin. People with one or more close 

relatives who have PD have an increased risk of 

developing the disease themselves, but the total 

risk is still about 

2 to 5 percent 

unless the family 

has a known gene 

mutation for 

the disease. An 

estimated 15 to 

25 percent of 

people with PD 

have a known 

relative with 

the disease. 

PD affects both men and women; however, the 

disorder affects 50 percent more men than women. 
8

In very rare cases, parkinsonian symptoms may 

appear in people before the age of 20. This condition 

is called juvenile parkinsonism. It often begins with 

dystonia and bradykinesia, and the symptoms often 

improve with levodopa medication. 

What are the symptoms of the disease?

The four primary symptoms of PD are: 

• Tremor. The tremor associated with PD has a 

characteristic appearance. Typically, the tremor 

takes the form of a rhythmic back-and-forth 

motion at a rate of 4-6 beats per second. It may 

involve the thumb and forefinger and appear 

as a “pill rolling” tremor. Tremor often begins 

in a hand, although sometimes a foot or the 

jaw is affected first. It is most obvious when 

the hand is at rest or when a person is under 

stress. Tremor usually disappears during sleep 

or improves with intentional movement. It is 

usually the first symptom that causes people 

to seek medical attention.

• Rigidity. Rigidity, or a resistance to movement, 

affects most people with PD. The muscles 

remain constantly tense and contracted so 

that the person aches or feels stiff. The rigidity 

becomes obvious when another person tries 

to move the individual’s arm, which will move 

only in ratchet-like or short, jerky movements 

known as “cogwheel” rigidity. 

• Bradykinesia. This slowing down of spontaneous 

and automatic movement is particularly 
9

frustrating because it may make simple tasks 

difficult. The person cannot rapidly perform 

routine movements. Activities once performed 

quickly and easily—such as washing or dressing—

may take much longer. There is often a decrease 

in facial expressions.

• Postural instability. Postural instability, or 

impaired balance, causes affected individuals 

to fall easily. 

PD does not affect everyone the same way, and the 

rate of progression and the particular symptoms 

differ among individuals. 

PD symptoms typically begin on one side of the 

body. However, the disease eventually affects both 

sides. Even after the disease involves both sides of 

the body, the symptoms are often less severe on one 

side than on the other.

Friends or family members may be the first to 

notice changes in someone with early PD. They 

may see that the person’s face lacks expression 

and animation (known as “masked face”) or that 

the person moves more slowly. 

Early symptoms of PD may be subtle and occur 

gradually. Affected people may feel mild tremors 

or have difficulty getting out of a chair. Activities 

may take longer to complete than in the past and 

individuals may note some stiffness in addition to 

slowness. They may notice that they speak too softly 

or that their handwriting is slow and looks cramped 

or small. This very early period may last a long 

time before the more classical and obvious motor 

(movement) symptoms appear.
PD does not affect 

everyone the same way, 

and the rate of progression 

and the symptoms differ 

among individuals.

10

As the disease progresses, 

the symptoms of Parkinson’s 

disease may begin to interfere 

with daily activities. Affected 

individuals may not be able 

to hold utensils steady or they may find that the 

shaking makes reading a newspaper difficult. People 

with PD often develop a so-called parkinsonian gait

that includes a tendency to lean forward, taking 

small quick steps as if hurrying (called festination), 

and reduced swinging in one or both arms. They 

may have trouble initiating movement (start 

hesitation), and they may stop suddenly as they 

walk (freezing). 

A number of other symptoms may accompany 

PD, and some can be treated with medication or 

physical therapy. 

• Depression. This common disorder may appear 

early in the course of the disease, even before 

other symptoms are noticed. Some people 

lose their motivation and become dependent 

on family members. Fortunately, depression 

typically can be treated successfully with 

antidepressant medications such as 

amytriptyline or fluoxetine. 

• Emotional changes. Some people with PD become 

fearful and insecure, while others may become 

irritable or uncharacteristically pessimistic. 

• Difficulty with swallowing and chewing. Muscles 

used in swallowing may work less efficiently in 

later stages of the disease. Food and saliva may 

collect in the mouth and back of the throat, which 

can result in choking or drooling. These problems 

may also make it difficult to get adequate nutrition. 
11

Speech-language therapists, occupational 

therapists (who help people learn new ways to 

perform activities of daily living), and dieticians 

can often help with these problems. 

• Speech changes. About half of all individuals 

with PD have speech difficulties that may be 

characterized as speaking too softly or in a 

monotone. Some may hesitate before speaking, 

slur, or speak too fast. A speech therapist may 

be able to help these individuals reduce some 

of these problems. 

• Urinary problems or constipation. In some people 

with PD, bladder and bowel problems can occur 

due to the improper functioning of the autonomic 

nervous system, which is responsible for regulating 

smooth muscle activity. Medications can effectively 

treat some of these symptoms.

• Skin problems. In PD, the skin on the face may 

become oily, particularly on the forehead and at 

the sides of the nose. The scalp may become oily 

too, resulting in dandruff. In other cases, the 

skin can become very dry. Standard treatments 

for skin problems can help. 

•

Sleep problems, which are common 

in PD, may include restless sleep, 

drowsiness, nightmares, or sudden 

sleep onset during the day.

Sleep problems. Sleep 

problems are common 

in PD and include 

difficulty staying 

asleep at night, restless 

sleep, nightmares and 

emotional dreams, and 

drowsiness or sudden 

sleep onset during 

the day. Another 

common problem is 
12

“REM behavior disorder,” in which people 

act out their dreams, potentially resulting in 

injury to themselves or their bed partners. The 

medications used to treat PD may contribute 

to some of these sleep issues. Many of these 

problems respond to specific therapies.

• Dementia or other cognitive problems. Some 

people with PD may develop memory problems 

and slow thinking. Cognitive problems become 

more severe in late stages of PD, and a diagnosis 

of Parkinson’s disease dementia (PDD) may 

be given. Memory, social judgment, language, 

reasoning, or other mental skills may be affected. 

There is currently no way to halt PD dementia, 

but drugs such as rivastigmine, donepezil, or 

memantine may help. The medications used 

to treat the motor symptoms of PD may cause 

confusion and hallucinations.

• Orthostatic hypotension. Orthostatic 

hypotension is a sudden drop in blood pressure 

when a person stands up from a lying-down 

or seated position. This may cause dizziness, 

lightheadedness, and, in extreme cases, loss of 

balance or fainting. Studies have suggested that, 

in PD, this problem results from a loss of nerve 

endings in the sympathetic nervous system that 

controls heart rate, blood pressure, and other 

automatic functions in the body. The medications 

used to treat PD may also contribute to this 

symptom. Orthostatic hypotension may improve 

by increasing salt intake. Physicians treating 

the disorder may also reduce anti-hypertension 

drug dosage or by prescribing medications such 

as fludrocortisone.
13

• Muscle cramps and 

Exercise may help to relieve the 

fatigue and loss of energy that 

people with PD often experience.

dystonia. The rigidity and 

lack of normal movement 

associated with PD often 

causes muscle cramps, 

especially in the legs and 

toes. Massage, stretching, 

and applying heat may 

help with these cramps. 

PD can also be associated 

with dystonia—sustained 

muscle contractions that 

cause forced or twisted 

positions. Dystonia in PD is 

often caused by fluctuations in the body’s level 

of dopamine. Management strategies may involve 

adjusting medications. 

• Pain. Many people with PD develop aching 

muscles and joints because of the rigidity and 

abnormal postures often associated with the 

disease. Treatment with levodopa and other 

dopaminergic drugs often alleviates these pains 

to some extent. Certain exercises may help. 

• Fatigue and loss of energy. Many people with 

PD often have fatigue, especially late in the 

day. Fatigue may be associated with depression 

or sleep disorders, but it may also result from 

muscle stress or from overdoing activity when 

the person feels well. Fatigue may also result 

from akinesia—trouble initiating or carrying 

out movement. Exercise, good sleep habits, 

staying mentally active, and not forcing too 

many activities in a short time may help to 

alleviate fatigue.
14

• Sexual dysfunction. Because of its effects on 

nerve signals from the brain, PD may cause 

sexual dysfunction. PD-related depression 

or use of certain medications may also cause 

decreased sex drive and other problems. 

People should discuss these issues with their 

physician as they may be treatable. 

Hallucinations, delusions, and other psychotic 

symptoms can be caused by the drugs prescribed 

for PD. Reducing PD medications dosages 

or changing medications may be necessary if 

hallucinations occur. If such measures are not 

effective, doctors sometimes prescribe drugs called 

atypical antipsychotics, which include clozapine 

and quetiapine. The typical antipsychotic drugs, 

which include haloperidol, worsen the motor 

symptoms of PD and should not be used.

What other diseases and conditions resemble 

Parkinson’s disease? 

A number of disorders can cause symptoms 

similar to those of PD. People with symptoms 

that resemble PD but that result from other 

causes are considered to have parkinsonism. 

Some of these disorders include: 

• Multiple system atrophy. Multiple system 

atrophy (MSA) refers to a set of slowly progressive 

disorders that affect the central and autonomic 

nervous systems. In MSA, the protein alphasynuclein forms harmful filament-like aggregates 

in the supporting cells in the brain called 
15

oligodenreoglia. MSA may have symptoms that 

resemble PD. It may also take a form that 

primarily produces poor coordination and 

slurred speech, or it may involve a combination 

of these symptoms. Other symptoms may 

include swallowing difficulties, male impotence, 

constipation, and urinary difficulties. The 

disorder previously called Shy-Drager syndrome 

refers to MSA with prominent orthostatic 

hypotension—a fall in blood pressure every time 

the person stands up. MSA with parkinsonian 

symptoms is sometimes referred to as MSA-P 

(or striatonigral degeneration), while MSA 

with poor coordination and slurred speech is 

sometimes called MSA-C (or olivopontocerebellar 

atrophy). Unfortunately, many of the symptoms 

of MSA either do not respond to PD medications 

or the response is minimal or short-lived.

Dementia with Lewy bodies is a neurodegenerative disorder associated with the same 

abnormal protein deposits, called Lewy bodies, found in Parkinson’s Disease. The 

drawing above shows a Lewy body.
16

• Dementia with Lewy bodies. Dementia with 

Lewy bodies is a neurodegenerative disorder 

associated with the same abnormal protein 

deposits (Lewy bodies) found in Parkinson’s 

disease but in widespread areas throughout 

the brain. Symptoms may range from primary 

parkinsonian symptoms such as bradykinesia, 

rigidity, tremor, and shuffling walk, to symptoms 

similar to those of Alzheimer’s disease (memory 

loss, poor judgment, and confusion). These 

symptoms may fluctuate, or wax and wane 

dramatically. Visual hallucinations are often 

one of the first symptoms, and individuals may 

suffer from other psychiatric disturbances 

such as delusions and depression. Cognitive 

problems also occur early in the course of the 

disease. Levodopa and other antiparkinsonian 

medications can help with the motor symptoms 

of Dementia with Lewy bodies, but they may 

make hallucinations and delusions worse, and 

affected individuals may require treatment 

with atypical antipsychotic medications. 

• Progressive supranuclear palsy. Progressive 

supranuclear palsy (PSP) is a rare, progressive 

brain disorder that causes problems with control 

of gait and balance. The symptoms of PSP are 

caused by a gradual deterioration of cells in 

the brain stem. People often tend to fall early 

in the course of PSP. One of the characteristic 

features of the disease is an inability to move 

the eyes properly, which some people describe 

as having blurred vision. People with PSP 

often show alterations of mood and behavior, 
17

including depression and apathy as well as 

mild dementia. PSP is often misdiagnosed 

because some of its symptoms are much like 

those of PD, Alzheimer’s disease, and other 

brain disorders. PSP symptoms usually do 

not respond to medication, or the response is 

minimal and short-lasting. PSP is characterized 

by aggregation of a protein called tau.

• Corticobasal degeneration. Corticobasal 

degeneration (CBD) results from atrophy 

of multiple areas of the brain, including the 

cerebral cortex and the basal ganglia. Initial 

symptoms may first appear on one side of 

the body, but eventually affect both sides. 

Symptoms are similar to some of the features 

found in PD, including rigidity, impaired 

balance, and problems with coordination. 

Often there is dystonia affecting one side of the 

body. Other symptoms may include cognitive 

and visual-spatial impairments, apraxia (loss 

of the ability to make familiar, purposeful 

movements), hesitant and halting speech, 

myoclonus (muscular jerks), and dysphagia 

(difficulty swallowing). Unlike PD, CBD usually 

does not respond to medication. Like PSP, it is 

characterized by deposits of the tau protein.

Several diseases, including MSA, CBD, and PSP, 

are sometimes referred to as “Parkinson’s-plus”

diseases because they have the symptoms of PD 

plus additional features. 
18

Post-traumatic parkinsonism occurs when parkinsonian symptoms develop after a 

severe head injury or frequent head trauma associated with boxing or other activities.

Parkinsonism resulting from 

neurological disorders

• Arteriosclerotic parkinsonism. Sometimes 

known as pseudoparkinsonism, vascular 

parkinsonism, or atherosclerotic parkinsonism, 

arteriosclerotic parkinsonism involves damage 

to the brain due to multiple strokes. Tremor 

is rare in this type of parkinsonism, while 

dementia and difficulties with gait are common. 

Antiparkinsonian drugs are of little help to 

people with this form of parkinsonism. 

• Post-traumatic parkinsonism. Also known as 

post-traumatic encephalopathy or “punch-drunk 

syndrome,” parkinsonian symptoms can develop 

after a severe head injury or frequent head 

trauma associated with boxing or other activities. 

This type of trauma can also cause a form of 

dementia called chronic traumatic encephalopathy. 
19

• Essential tremor. Sometimes called benign 

essential tremor or familial tremor, this common 

condition tends to run in families and progresses 

slowly over time. The tremor is usually equal 

in both hands and increases when the hands 

are moving. It may involve the head but usually 

spares the legs. Essential tremor is not the same 

as Parkinson’s disease and does not usually lead 

to it, although in some cases the two conditions 

may overlap in one person. People with essential 

tremor have no other parkinsonian features. 

Essential tremor does not respond to levodopa 

or to most other PD drugs, but there are 

medications to treat it. 

• Normal pressure hydrocephalus. Normal 

pressure hydrocephalus (NPH) is an abnormal 

increase of cerebrospinal fluid (CSF) in the 

brain’s ventricles, or cavities. This causes the 

ventricles to enlarge, putting pressure on the 

brain. Symptoms include problems with walking, 

impaired bladder control leading to increased 

urinary frequency or incontinence, and 

progressive mental impairment and dementia. 

The person may also have a general slowing of 

movements or may complain that his or her feet 

feel “stuck.” These symptoms may sometimes 

be mistaken for PD. They do not respond 

to Parkinson’s medications. Brain scans, 

intracranial pressure monitoring, and other 

tests can help to diagnose NPH. NPH can 

sometimes be treated by surgically implanting 

a CSF shunt that drains excess cerebrospinal 

fluid into the abdomen, where it is absorbed. 
20

• Parkinsonism accompanying other 

conditions. Parkinsonian symptoms appear 

in individuals with other, clearly distinct 

neurological disorders such as Wilson’s disease, 

Huntington’s disease, Alzheimer’s disease, 

spinocerebellar ataxias, and Creutzfeldt-Jakob 

disease. Each of these disorders has specific 

features that help to distinguish it from PD.

Environmental causes

• Postencephalitic parkinsonism. Just after the 

first World War, the viral disease encephalitis 

lethargica affected almost 5 million people 

throughout the world, and then suddenly 

disappeared in the 1920s. Known as sleeping 

sickness in the United States, this disease 

killed one-third of its victims and led to postencephalitic parkinsonism in many others. 

This resulted in a movement disorder that 

appeared sometimes years after the initial 

illness. (In 1973, neurologist Oliver Sacks 

published Awakenings, an account of his 

work in the late 1960s with surviving postencephalitic patients in a New York hospital. 

Using the then-experimental drug levodopa, 

Dr. Sacks was able to temporarily “awaken” 

these individuals from their statue-like 

state). In rare cases, other viral infections, 

including western equine encephalomyelitis, 

eastern equine encephalomyelitis, and 

Japanese B encephalitis, have caused 

parkinsonian symptoms. 
21

•

Many disorders can 

cause symptoms 

similar to those of 

Parkinson’s disease.

Drug-induced 

parkinsonism. A 

reversible form 

of parkinsonism 

sometimes results from use of certain drugs, such 

as chlorpromazine and haloperidol, which are 

typically prescribed for patients with psychiatric 

disorders. Some drugs used for stomach disorders 

(metoclopramide), high blood pressure (reserpine), 

and others such as valproate can cause tremor 

and bradykinesia. Stopping the medication or 

lowering the dosage of these medications usually 

causes the symptoms to go away. 

• Toxin-induced parkinsonism. Some toxins can 

cause parkinsonism by various mechanisms. 

The chemical MPTP also causes a permanent 

form of parkinsonism that closely resembles 

PD. Investigators discovered this reaction in 

the 1980s when heroin addicts in California who 

had taken an illicit street drug contaminated with 

MPTP began to develop severe parkinsonism. 

This discovery, which showed that a toxic 

substance could damage the brain and produce 

parkinsonian symptoms, led to a dramatic 

breakthrough in Parkinson’s research.

• Parkinsonism-dementia complex of Guam.

This disease occurs among the Chamorro 

populations of Guam and the Mariana Islands 

and may be accompanied by a motor neuron 

disease resembling amyotrophic lateral sclerosis 

(Lou Gehrig’s disease). The course of the disease 

is rapid, with death typically occurring within 

5 years. 
22

How is Parkinson’s disease diagnosed?

There are currently no blood or laboratory tests 

that diagnose sporadic PD. Therefore the diagnosis 

is based on medical history and a neurological 

examination. In some cases PD can be difficult to 

diagnose accurately early on in the course of the 

disease. Early signs and symptoms of PD may 

sometimes be dismissed as the effects of normal aging. 

Doctors may sometimes request brain scans or 

laboratory tests in order to rule out other disorders. 

However, computed tomography (CT) and magnetic 

resonance imaging (MRI) brain scans of people 

with PD usually appear normal. Since many other 

diseases have similar features but require different 

treatments, making a precise diagnosis is important 

so that people can receive the proper treatment. 

What is the prognosis?

The average life expectancy of a person with PD is 

generally the same as for people who do not have 

the disease. Fortunately, there are many treatment 

options available for people with PD. 

However, in the late stages, PD may no longer respond 

to medications and can become associated with serious 

complications such as choking, pneumonia, and falls. 

PD is a slowly progressive disorder. It is not 

possible to predict what course the disease will 

take for an individual person. One commonly 

used scale neurologists use for describing how the 

symptoms of PD have progressed in a patient is 

the Hoehn and Yahr scale. 
23

Hoehn and Yahr Staging of Parkinson’s Disease

Stage one – symptoms on one side of the body only.

Stage two – symptoms on both sides of the body. 

No impairment of balance.

Stage three – balance impairment. Mild to moderate 

disease. Physically independent.

Stage four – severe disability, but still able to walk 

or stand unassisted.

Stage five – wheelchair-bound or bedridden 

unless assisted. 

Another commonly used scale is the Movement 

Disorders Society-Unified Parkinson’s Disease 

Rating Scale (MDS-UPDRS). This four-part scale 

measures motor movement in PD: non-motor 

experiences of daily living, motor experiences 

of daily living, motor examination, and motor 

complications. Both the Hoehn and Yahr scale 

and the MDS-UPDRS are used to describe 

how individuals are faring and to help assess 

treatment response. 

How is the disease treated?

At present, there is no cure for PD, but medications 

or surgery can often provide improvement in the 

motor symptoms.
24

Drug Therapy

Medications for PD fall into three categories. The 

first category includes drugs that increase the level 

of dopamine in the brain. The most common drugs 

for PD are dopamine precursors—substances such 

as levodopa that cross the blood-brain barrier 

and are then changed into dopamine. Other drugs 

mimic dopamine or prevent or slow its breakdown.

The second category of PD drugs affects other 

neurotransmitters in the body in order to ease 

some of the symptoms of the disease. For example, 

anticholinergic drugs interfere with production 

or uptake of the neurotransmitter acetylcholine. 

These can be effective in reducing tremors. 

The third category of drugs prescribed for PD 

includes medications that help control the nonmotor symptoms of the disease, that is, the 

symptoms that don’t affect movement. For 

example, people with PD-related depression 

may be prescribed antidepressants. 

• Levodopa/Carbidopa. The cornerstone of 

therapy for PD is the drug levodopa (also called 

L-dopa). Nerve cells can use levodopa to make 

dopamine and replenish the brain’s reduced 

supply. People cannot simply take dopamine pills 

because dopamine does not easily pass through 

the blood-brain barrier. (The blood-brain 

barrier is a protective lining of cells inside blood 

vessels that regulate the transport of oxygen, 

glucose, and other substances in the brain.) 

Usually, people are given levodopa combined 

with another substance called carbidopa. When 

added to levodopa, carbidopa prevents the 
25

conversion of levodopa into dopamine except 

for in the brain; this stops or diminishes the 

side effects due to dopamine in the bloodstream. 

Levodopa/carbidopa is often very successful at 

reducing or eliminating the tremors and other 

motor symptoms of PD during the early stages 

of the disease. It allows the majority of people 

with PD to extend the period of time in which 

they can lead active, productive lives. 

Although levodopa/carbidopa helps most people 

with PD, not all symptoms respond equally to 

the drug. Levodopa usually helps most with 

bradykinesia and rigidity. Problems with 

balance may not respond. 

People often see noticeable improvement in their 

symptoms after starting levodopa/carbidopa 

therapy. However, they may need to increase the 

dose gradually for maximum benefit. Levodopa 

is often so effective that some people may not 

show symptoms during the early stages of the 

disease as long as they take the medicine. But 

levodopa is not a cure. Although it can reduce 

the symptoms of PD, it does not replace lost 

nerve cells and it does not stop the progression 

of the disease. 

Levodopa/carbidopa can have a variety of 

side effects. The most common initial side 

effects include nausea, low blood pressure, 

and restlessness. The nausea and vomiting 

caused by levodopa are greatly reduced by the 

right combination of levodopa and carbidopa. 

The drug also can cause drowsiness or sudden 

sleep onset, which can make driving and 

other activities dangerous. Long-term use 
26

of levodopa sometimes 

causes hallucinations 

and psychosis. 

Presently, there is no cure for PD, however, 

medications or surgery may improve motor 

symptoms. When recommending treatment, 

a doctor will assess a person’s symptoms 

and then tailor therapy to the person’s 

particular condition.

Dyskinesias, or involuntary 

movements such twisting 

and writhing, commonly 

develop in people who take 

levodopa over an extended 

period. These movements 

may be either mild or 

severe. Some doctors start 

younger individuals with PD 

on drugs that act directly 

like dopamine itself and add 

levodopa later in the course of the disease. The 

dosage of levodopa is sometimes reduced in order 

to lessen these drug-induced movements. The 

drug amantadine may help control dyskinesias 

but if dyskinesias are severe, surgical treatment 

such as deep brain stimulation may be 

considered (see description in “Surgery”). 

Other difficulties may be encountered later 

in the disease course. People with PD may 

begin to notice more pronounced symptoms 

before their first dose of medication in the 

morning and between doses as the period of 

effectiveness after each dose begins to shorten, 

called the wearing-off effect. People experience 

sudden, unpredictable “off periods,” where 

the medications do not seem to be working. 

One approach to alleviating these side effects 

is to take levodopa more often and in smaller 

amounts. People with PD should never stop 

taking levodopa without their physician’s input, 
27

because rapidly withdrawing the drug can have 

potentially serious side effects. 

In addition to levodopa/carbidopa, there are other 

available treatments:

• Dopamine agonists. These drugs, which include 

apomorphine, pramipexole, ropinirole, and 

rotigotine, mimic the role of dopamine in the 

brain. They can be given alone or with levodopa. 

They are somewhat less effective than levodopa 

in treating PD symptoms, but work for longer 

periods of time. Many of the potential side effects 

are similar to those associated with the use of 

levodopa, including drowsiness, sudden sleep 

onset, hallucinations, confusion, dyskinesias, 

edema (swelling due to excess fluid in body 

tissues), nightmares, and vomiting. In rare 

cases, they can cause an uncontrollable desire to 

gamble, hypersexuality, or compulsive shopping.

• MAO-B inhibitors. These drugs inhibit the 

enzyme monoamine oxidase B, or MAO-B, which 

breaks down dopamine in the brain. MAO-B 

inhibitors cause dopamine to accumulate in 

surviving nerve cells and reduce the symptoms 

of PD. Studies supported by the NINDS have 

shown that selegiline (also called deprenyl) can 

delay the need for levodopa therapy by up to 

a year or more. When selegiline is given with 

levodopa, it appears to enhance and prolong 

the response to levodopa and thus may reduce 

wearing-off. Selegiline is usually well-tolerated, 

although side effects may include nausea, 

orthostatic hypotension, or insomnia. It should 

not be taken with the antidepressant fluoxetine 

or the sedative meperidine, because combining 
28

selegiline with these drugs can be harmful. The 

drug rasagiline is used in treating the motor 

symptoms of PD with or without levodopa. 

Whether rasagiline slows progression of PD is 

still controversial.

• COMT inhibitors. COMT stands for catecholO-methyltransferase, another enzyme that 

breaks down dopamine. The drug entacapone 

and tolcapone prolong the effects of levodopa 

by preventing the breakdown of dopamine. 

COMT inhibitors can decrease the duration of 

“off periods” of one’s dose of levodopa. The 

most common side effect is diarrhea. The drugs 

cause nausea, sleep disturbances, dizziness, 

urine discoloration, abdominal pain, low blood 

pressure, or hallucinations. In a few rare cases, 

tolcapone has caused severe liver disease, and 

people taking tolcapone need regular monitoring 

of their liver function. 

• Amantadine. This antiviral drug can help 

reduce symptoms of PD and levodopa-induced 

dyskinesia. It is often used alone in the early 

stages of the disease. It may also be used with an 

anticholinergic drug or levodopa. After several 

months, amantadine’s effectiveness wears off in 

up to half of the people taking it. Amantadine’s 

side effects may include insomnia, mottled skin, 

edema, agitation, or hallucinations. Researchers 

are not certain how amantadine works in PD, 

but it may increase the effects of dopamine. 

• Anticholinergics. These drugs, which 

include trihexyphenidyl, benztropine, and 

ethopropazine, decrease the activity of the 

neurotransmitter acetylcholine and can be 
29

particularly effective for tremor. Side effects 

may include dry mouth, constipation, urinary 

retention, hallucinations, memory loss, blurred 

vision, and confusion. 

When recommending a course of treatment, a doctor 

will assess how much the symptoms disrupt the 

person’s life and then tailor therapy to the person’s 

particular condition. Since no two people will react 

the same way to a given drug, it may take time 

and patience to get the dose just right. Even then, 

symptoms may not be completely alleviated. 

Medications to Treat the Motor Symptoms 

of Parkinson’s Disease

Category Generic Brand name

Drugs that increase 

brain levels of dopamine

Levodopa/carbidopa Parcopa, Sinemet

Drugs that mimic dopamine 

(dopamine agonists)

Apomorphine

Pramipexole

Ropinirole

Rotigotine

Apokyn

Mirapex

Requip

Neupro

Drugs that inhibit 

dopamine breakdown 

(MAO-B inhibitors)

Rasagiline 

Selegiline (deprenyl)

Azilect

Eldepryl, Zelapar

Drugs that inhibit 

dopamine breakdown 

(COMT inhibitors)

Entacapone

Tolcapone

Comtan

Tasmar

Drugs that decrease the 

action of acetylcholine 

(anticholinergics)

Benztropine

Ethopropazine

Trihexyphenidyl

Cogentin

Parsidol

Artane

Drugs with an unknown 

mechanism of action for PD

Amantadine Symmetrek
30

Surgery

Before the discovery of levodopa, surgery was an 

option for treating PD. Studies in the past few 

decades have led to great improvements in surgical 

techniques, and surgery is again considered for 

people with PD for whom drug therapy is no 

longer sufficient. 

Pallidotomy and Thalamotomy. The earliest types 

of surgery for PD involved selectively destroying 

specific parts of the brain that contribute to PD 

symptoms. Surgical techniques have been refined 

and can be very effective for the motor symptoms 

of PD. The most common lesion surgery is called 

pallidotomy. In this procedure, a surgeon selectively 

destroys a portion of the brain called the globus 

pallidus. Pallidotomy can improve symptoms of 

tremor, rigidity, and bradykinesia, possibly by 

interrupting the connections between the globus 

pallidus and the striatum or thalamus. Some 

studies have also found that pallidotomy can 

improve gait and balance and reduce the amount 

of levodopa people require, thus reducing druginduced dyskinesias. Another procedure, called 

thalamotomy, involves surgically destroying part 

of the thalamus; this approach is useful primarily 

to reduce tremor. 

Because these procedures cause permanent 

destruction of small amounts of brain tissue, 

they have largely been replaced by deep brain 

stimulation for treatment of PD. However, a new 

method using focused ultrasound from outside 

the head is being tested because it creates lesions 

without the need for surgery.
31

Deep brain stimulation, which involves 

surgical stimulation of the brain, helps to 

block signals that cause many of the motor 

symptoms of PD.

Deep Brain Stimulation. 

Deep brain stimulation, 

or DBS, uses an electrode 

surgically implanted 

into part of the brain, 

typically the subthalamic 

nucleus or the globus 

pallidus. Similar to a 

cardiac pacemaker, a 

pulse generator (battery 

pack) that is implanted 

in the chest area under 

the collarbone sends 

finely controlled electrical 

signals to the electrode(s) 

via a wire placed under 

the skin. When turned on using an external wand, 

the pulse generator and electrodes painlessly 

stimulate the brain in a way that helps to block 

signals that cause many of the motor symptoms 

of PD. DBS is approved by the U.S. Food and 

Drug Administration and is widely used as a 

treatment for PD. 

DBS can be used on one or both sides of the brain. 

If it is used on just one side, it will affect symptoms 

on the opposite side of the body. DBS is primarily 

used to stimulate one of three brain regions: the 

subthalamic nucleus, the globus pallidus interna, 

or the thalamus. Stimulation of either the globus 

pallidus or the subthalamic nucleus can reduce 

tremor, bradykinesia, and rigidity. Stimulation of 

the thalamus is useful primarily for reducing tremor. 
32

People who initially responded well to treatment 

with levodopa tend to respond well to DBS. 

While the motor function benefits of DBS can be 

substantial, it usually does not help with speech 

problems, “freezing,” posture, balance, anxiety, 

depression, or dementia. 

One advantage of DBS compared to pallidotomy 

and thalamotomy is that the electrical current can 

be turned off using a handheld device. The pulse 

generator also can be externally programmed. 

Individuals must return to the medical center 

frequently for several months after DBS surgery 

in order to have the stimulation adjusted very 

carefully to give the best results. After a few 

months, the number of medical visits usually 

decreases significantly, though individuals may 

occasionally need to return to the center to have 

their stimulator checked. Currently, the battery 

for the pulse generator must be surgically replaced 

every three to five years. DBS does not stop 

PD from progressing, and some problems may 

gradually return. DBS is not a good option for 

everyone. It is generally appropriate for people 

with levodopa-responsive PD who have developed 

dyskinesias or other disabling “off” symptoms 

despite drug therapy. It is not generally an option 

for people with memory problems, hallucinations, 

severe depression, poor health, or a poor response 

to levodopa. DBS has not been demonstrated 

to be of benefit for “atypical” parkinsonian 

syndromes such as multiple system atrophy, 

progressive supranuclear palsy, or post-traumatic 

parkinsonism, which also do not improve with 

Parkinson’s medications. 
33

As with any brain surgery, DBS has potential 

complications, including stroke or brain hemorrhage. 

These complications are rare, however. There is also 

a risk of infection, which may require antibiotics or 

even replacement of parts of the DBS system. 

Complementary and Supportive Therapies

A wide variety of complementary and supportive 

therapies may be used for PD. Among these 

therapies are standard physical, occupational, and 

speech therapy techniques, which can help with 

such problems as gait and voice disorders, tremors 

and rigidity, and cognitive decline. Other types of 

supportive therapies include: 

Diet. At this time there are no specific vitamins, 

minerals, or other nutrients that have any proven 

therapeutic value in PD. An NINDS clinical study of 

the dietary supplement coenzyme Q10 was stopped 

in 2011 when results from an interim analysis 

showed active treatment with the supplement was 

unlikely to demonstrate a statistically significant 

difference than from a placebo. The NINDS and 

other components of the National Institutes of 

Health are funding research to determine if caffeine, 

antioxidants, and other dietary factors may be 

beneficial for preventing or treating PD. While 

there is currently no proof that any specific dietary 

factor is beneficial, a normal, healthy diet can 

promote overall well-being for people with PD just 

as it would for anyone else. Eating a fiber-rich diet 

and drinking plenty of fluids also can help alleviate 

constipation. A high protein diet, however, may limit 

levodopa’s absorption, highlighting the importance 

of the timing of medications. 
34

Exercise. Exercise can help people with PD improve 

their mobility and flexibility. Some doctors prescribe 

physical therapy or muscle-strengthening exercises 

to tone muscles and to put underused and rigid 

muscles through a full range of motion. The effects 

of exercise on disease progression are not known, 

but it may improve body strength so that the person 

is less disabled. Exercises also improve balance, 

helping people minimize gait problems, and can 

strengthen certain muscles so that people can speak 

and swallow better. Exercise can improve emotional 

well-being and general physical activity, such as 

walking, gardening, swimming, calisthenics, and 

using exercise machines, can have other benefit. 

An NINDS-funded clinical trial demonstrated the 

benefit of tai chi exercise compared to resistance or 

stretching exercises.2

 People with PD should always 

check with their doctors before beginning a new 

exercise program. 

Other complementary and supportive therapies 

that are used by some individuals with PD include 

massage therapy, yoga, hypnosis, acupuncture, and 

the Alexander technique, which optimizes posture 

and muscle activity. 

Another important therapeutic approach involves 

speech and swallowing evaluation and therapy. 

Certain techniques can help with the low voice volume 

that individuals with Parkinson’s often experience.

2 Li, F. et al. “Tai chi and postural stability in patients with 

Parkinson’s disease.” New England Journal of Medicine. 

February 9, 2012. Volume 366(6), pages 511-9.
35

Some complementary and supportive therapies used by people with PD include yoga, 

massage therapy, acupuncture, and hypnosis.

How can people cope with 

Parkinson’s disease? 

While PD usually progresses slowly, eventually 

daily routines may be affected—from socializing 

with friends to earning a living and taking care of 

a home. These changes can be difficult to accept. 

Support groups can help people cope with the 

disease’s emotional impact. These groups also 

can provide valuable information, advice, and 

experience to help people with PD, their families, 

and their caregivers deal with a wide range of 

issues, including locating doctors familiar with the 

disease and coping with physical limitations. A list 

of national organizations that can help people locate 

support groups in their communities appears at 

the end of this information. Individual or family 

counseling may also help people find ways to cope 

with PD. 

People with PD may also benefit from being 

proactive and finding out as much as possible 

about the disease in order to alleviate fear of the 

unknown and to take a positive role in maintaining 
36

their health. Many people with PD continue to work 

either full- or part-time, although they may need to 

adjust their schedule and working environment to 

accommodate their symptoms. 

Can scientists predict or prevent 

Parkinson’s disease?

In most cases, there is no way to predict or prevent 

sporadic PD. However, researchers are looking for a 

biomarker—a biological abnormality that all people 

with PD might share—that could be detected by 

screening techniques or by a simple chemical test 

given to people who do not yet have any parkinsonian 

symptoms. This could help doctors identify people 

at risk of the disease. It also might allow them to find 

treatments that will stop the disease process in the 

early stages. Studies demonstrated that synuclein 

builds up in nerve cells years before symptoms 

occur. Loss of a sense of smell, constipation, restless 

legs, and REM sleep disorder are potentially caused 

by these early changes.

One important area of research in this domain involves 

imaging techniques, such as special MRI techniques 

or nuclear imaging techniques currently under study 

at the National Institutes of Health and elsewhere.

In rare cases, where people have a clearly inherited 

form of PD, researchers can test for known gene 

mutations as a way of determining an individual’s 

risk of developing the disease. However, this genetic 

testing can have far-reaching implications and 

people should carefully consider whether they 

want to know the results of such tests. 
37

What research is being done?

The mission of the National Institute of 

Neurological Disorders and Stroke (NINDS) is 

to seek fundamental knowledge about the brain 

and nervous system and to use the knowledge 

to reduce the burden of neurological disease. 

The NINDS is a component of the National 

Institutes of Health (NIH), the leading supporter 

of biomedical research in the world. The NINDS 

conducts and supports three types of research: 

basic—scientific discoveries in the lab, clinical—

developing and studying therapeutic approaches 

to Parkinson’s disease, and translational—

focused on tools and resources that speed the 

development of therapeutics into practice. The 

goals of NINDS-supported research are to better 

understand and diagnose PD, develop new 

treatments, and ultimately, prevent PD. NINDS 

also supports training for the next generation of 

PD researchers and clinicians, and serves as an 

important source of information for people with 

PD and their families.

A long-term NINDS research and planning 

strategy led to the NINDS-hosted January 

2014 conference, “Parkinson’s Disease 2014: 

Advancing Research, Improving Lives,” at 

which neuroscientists, physicians, public and 

private organization representatives, and people 

with Parkinson’s disease discussed the highest 

research priorities, ranging from lab discoveries to 

developing new therapies for PD (see www.ninds.

nih.gov/research/parkinsonsweb/PD2014/). 
38

Scientists involved in the Parkinson’s Disease Biomarkers Program hope that finding 

characteristics that may indicate risk of the disease will speed the development of 

new PD therapeutics.

The Parkinson’s Disease Biomarkers Programs 

(PDBP), a major NINDS initiative, is aimed at 

discovering ways to identify individuals at risk for 

developing PD and to track the progression of the 

disease. Identifying biomarkers (signs that may 

indicate risk of a disease and improve diagnosis) 

will speed the development of novel therapeutics 

for PD. Projects are actively recruiting volunteers 

at sites across the U.S. The NINDS also collaborates 

with the Michael J. Fox Foundation for Parkinson’s 

Research (MJFF) on BioFIND, a project collecting 

biological samples and clinical data from healthy 

volunteers and those with PD. For more information 

about the PDPB and how you can get involved, 

please visit the PDBP website at http://pdbp.ninds.

nih.gov/.
39

The NINDS Morris K. Udall Centers of 

Excellence for Parkinson’s Disease Research 

program—a central component of NINDS PD 

research—was established in 1997 to find the 

fundamental causes of PD and better diagnose 

and treat people with PD. The NINDS currently 

funds 10 Udall Centers across the country, where 

researchers are examining PD disease mechanisms, 

the genetic contributions to PD, and potential 

therapeutic targets and treatment strategies. To 

learn more about the NINDS Udall Centers, see 

www.ninds.nih.gov/udall.

Parkinson’s Disease Clinical Studies offer an 

opportunity to help researchers find better ways to 

safely detect, treat, or prevent PD and therefore 

hope for individuals now and in the future. NINDS 

conducts clinical studies on Parkinson’s disease at 

the NIH research campus in Bethesda, Maryland, 

and supports PD studies at medical research 

centers throughout the United States. But studies 

can be completed only if people volunteer to 

participate. By participating in a clinical study, 

healthy individuals and people living with 

Parkinson’s disease can greatly benefit the lives 

of those affected by this disorder. Talk with your 

doctor about clinical studies and help to make 

the difference in improving the quality of life for 

all people with Parkinson’s disease. For more 

information about NINDS clinical trials on PD, see 

www.clinicaltrials.gov and search for “Parkinson 

AND NINDS.” Current studies include genetics 

and PD, search for PD biomarkers, experimental 

therapies and other treatment options, diagnostic 

imaging, brain control and movement disorders, 

DBS, and exercise and PD. 
40

Animal models: These are valuable tools for 

scientists studying disease mechanisms to develop 

new treatments for people with PD. For example, 

a study of the drug isradipine—which had been 

shown in animal models to have a protective effect 

on dopaminergic neurons—is being tested for a 

similar neuroprotective effect in humans.

Cognition and Dementia: Mild cognitive 

impairment is common in PD, sometimes in its 

early stages, and some people develop dementia 

in the disease’s later stages. The NINDS has 

funded research using neuroimaging to predict 

which individuals with PD might develop 

cognitive impairment.

Deep Brain Stimulation (DBS): NINDS has been 

a pioneer in the study and development of DBS, 

which is now considered a standard treatment 

option for some people living with PD whose 

symptoms no longer respond to PD medications. 

While NIH supported research on brain circuitry 

was critical to the development of DBS, NINDS 

research continues to fine-tune the optimal site 

within the brain to implant the DBS electrode to 

help even more people with PD regain function. 

Researchers are continuing to study DBS and to 

develop ways of improving it. A two-part study 

funded by the NINDS and the Department of 

Veterans Affairs first compared bilateral DBS 

to best medical therapy, including medication 

adjustment and physical therapy. Bilateral DBS 

showed overall superiority to best medical therapy 

at improving motor symptoms and quality of life. 

The second part of the study, involving nearly 

300 patients, compared subthalamic nucleus (STN) 
41

DBS to globus pallidus interna (GPI) DBS. The two 

groups reported similar improvements in motor 

control and quality of life in scores on the Unified 

Parkinson’s Disease Rating Scale. On a variety of 

neuropsychological tests, there were no significant 

differences between the two groups. However, the 

STN DBS group experienced a greater decline 

on a test of visuomotor processing speed, which 

measures how quickly someone thinks and acts on 

information. Also, the STN DBS group had slight 

worsening on a standard assessment of depression, 

while the GPI DBS group had slight improvement on 

the same test. 

Other clinical studies hope to determine the best 

part of the brain to receive stimulation and to 

determine the long-term effects of this therapy. 

In addition, NINDS-supported researchers are 

developing and testing improved implantable 

pulse generators and conducting studies to 

better understand the therapeutic effect of 

neurostimulation on the brain.

 For more information about current studies on 

deep brain stimulation and Parkinson’s disease, 

see www.clinicaltrials.gov and search for “deep 

brain stimulation AND Parkinson AND NINDS.”

Environmental studies: Risk factors such as 

repeated occupational exposure to certain 

pesticides and chemical solvents may influence 

who develops PD. A NINDS-funded research 

consortium is hunting for environmental risk 

factors that increase susceptibility to developing 

PD before age 50. For example, NINDS-funded 

researchers analyzed the occupational histories 

of twins in which one of the pair developed PD. 
42

In a recent study to evaluate three forms of exercise, 

researchers found that tai chi led to the greatest overall 

improvements in balance and stability for people with 

mild to moderate PD.

Based on estimates 

of exposure to six 

chemicals previously 

linked to PD, the 

researchers concluded 

that two of the 

common solvents were 

significantly linked to 

development of PD. 

(See www.ninds.nih.

gov/news_and_events/

news_articles/solvents_

PD_twins.htm)

Exercise: Exercise routines are often recommended 

to help individuals with PD maintain movement 

and balance necessary for everyday living. A recent 

NINDS-funded study evaluated three different 

forms of exercise—resistance training, stretching, 

and tai chi—and found that tai chi led to the 

greatest overall improvements in balance and 

stability for people with mild to moderate PD. 

A current trial is studying the effects of two levels 

of exercise in people who have been recently 

diagnosed with PD. For more information, see 

www.ninds.nih.gov/disorders/clinical_trials/

NCT01506479.htm.

Genetic studies: A better understanding of genetic 

risk factors is playing a critical role in elucidating 

PD disease mechanisms. A 2011 NINDS workshop 

led to an analysis of data from PD genome-wide 

studies around the world, to correlate genetic 

variants and common traits among people with PD. 

The workshop contributed to the development of 

NeuroX, the first DNA chip that can identify genetic 
43

changes in persons at risk for a number of late-onset 

neurodegenerative diseases, including PD. Another 

NINDS collaborative, the Consortium On Risk 

for Early-onset Parkinson’s Disease (CORE PD), 

hopes to identify the genetic factors that contribute 

to the development of early-onset PD. Current 

clinical studies include the genetic connection 

to memory and motor behavior, the search for 

genes that may increase the risk of PD and related 

neurodegenerative disorders, and identifying 

biomarkers for PD. For more information on these 

studies, see www.clinicaltrials.gov and search for 

“gene AND NINDS AND Parkinson.” 

Mitochondria: These cellular energy factories 

may play a central role in PD. NINDS-funded 

scientists have found that hundreds of genes 

involved in mitochondrial function are less active 

in people with PD. Drugs that target genes involved 

in mitochondrial function could perhaps slow 

progression of the disease.

Motor complications: Involuntary movement, 

including dyskinesia (difficulty controlling intended 

muscle movement), as well as tremor, dystonia 

(involuntary muscle contractions), freezing of 

gait (inability to start walking), and other motor 

complications become evident as PD progresses; 

these symptoms are often difficult to treat. NINDS 

scientists have studied the safety and effectiveness 

of drugs and interventions in alleviating motor 

symptoms in persons with PD. For example, basic 

research using adenosine found it could improve 

motor complications associated with PD. A current 

NINDS clinical study of motor complications is 

testing an at-home device to evaluate PD movement 
44

symptoms while performing different tasks. For 

more information, see www.clinicaltrials.gov/ct2/

show/NCT01905839.

Nerve growth factors: Growth factors are proteins 

involved in nervous system formation and are of 

interest to researchers studying neurodegenerative 

diseases. One small clinical trial will assess the 

safety, tolerability, and potential clinical effects 

of gene therapy with Glial Derived Neurotrophic 

Factor (GDNF)—a protein that may help protect 

dopamine-producing nerve cells. This trial for 

individuals with advanced PD is based on NINDSsponsored research showing that an advanced 

viral technique for delivery of the GDNF gene 

into the brain improves the health and function 

of the dopamine neurons in animal models of PD. 

For more information, see www.clinicaltrials.gov/

ct2/show/NCT01621581.

Scientists are looking at various types of 

cells, including stem cells, as opportunities 

for PD drug discovery.

Neuroprotective Drugs: 

NINDS supports basic, clinical, 

and translational research 

aimed at protecting nerve cells 

from the damage caused by PD. 

The NINDS-funded NeuroNext 

Network is designed to test 

new therapies and to validate 

biomarkers in a number 

of neurological disorders, 

including Parkinson’s disease. 

For more information, see 

http://www.neuronext.org/.

Stem cells: Scientists are 

exploring various types of cells, 

including induced pluripotent 
45

stem cells (iPSCs), as opportunities for PD drug 

discovery. iPSC technology is used to define disease 

mechanisms and discover the most promising 

treatments for sporadic PD. To pursue this area 

of research, NINDS established a PD cell research 

consortium in 2009 in collaboration with the Michael 

J. Fox Foundation and the Parkinson’s Disease 

Foundation. For more information, see www.

ninds.nih.gov/news_and_events/news_articles/

pressrelease_nih_stem_cells.htm or http://

stemcells.nih.gov/.

Where can I go for more information?

For more information on neurological disorders or 

research programs funded by the National Institute 

of Neurological Disorders and Stroke, contact 

the Institute’s Brain Resources and Information 

Network (BRAIN) at:

BRAIN

P.O. Box 5801

Bethesda, MD 20824

800-352-9424

http://www.ninds.nih.gov

Information also is available from the following 

organizations:

American Parkinson Disease Association

135 Parkinson Avenue

Staten Island, NY 10305-1425

718-981-8001

800-223-2732

Young Onset Center 877-223-3801

http://www.apdaparkinson.org
46

The Bachmann-Strauss Dystonia 

& Parkinson Foundation 

Fred French Building

551 Fifth Avenue, Suite 520

New York, NY 10176

212-682-9900

http://www.dystonia-parkinson.org

The Michael J. Fox Foundation for 

Parkinson’s Research 

Grand Central Station

P.O. Box 4777

New York, NY 10163-4777

212-509-0995

800-708-7644 

http://www.michaeljfox.org

National Parkinson Foundation

200 SE 1st Street, Suite 800

Miami, FL 33131

800-473-4636

http://www.parkinson.org

Parkinson Alliance 

P.O. Box 308

Kingston, NJ 08528

609-688-0870

800-579-8440

http://www.parkinsonalliance.org

Parkinson’s Action Network

1025 Vermont Avenue, NW, Suite 1120

Washington, DC 20005

202-638-4101

800-850-4726

http://www.parkinsonsaction.org
47

Parkinson’s Disease Foundation

1359 Broadway, Suite 1509

New York, NY 10018

212-923-4700

800-457-6676

http://www.pdf.org

Parkinson’s Institute and Clinical Center

675 Almanor Avenue

Sunnyvale, CA 94085

408-734-2800

800-655-2273

http://www.thepi.org

Parkinson’s Resource Organization

74-090 El Paseo, Suite 104

Palm Desert, CA 92260

760-773-5628

877-775-4111

http://www.parkinsonsresource.org

Davis Phinney Foundation 

1772 14th Street, Suite 150

Boulder, CO 80302

303-733-3340

866-358-0285

http://www.davisphinneyfoundation.org

Tuchman Foundation

4422 Route 27

P.O. Box 582

Kingston, NJ 08528

609-924-6006
48

Glossary

akinesia — trouble initiating or carrying out movements.

anticholinergic drugs — drugs that interfere with 

production or uptake of the neurotransmitter 

acetylcholine.

bradykinesia — gradual loss of spontaneous movement.

corpus striatum — a part of the brain that helps 

regulate motor activities. 

deep brain stimulation — a treatment that uses 

an electrode implanted into part of the brain to 

stimulate it in a way that temporarily inactivates 

some of the signals it produces. 

dopamine — a chemical messenger, deficient 

in the brains of people with PD, that transmits 

impulses from one nerve cell to another. 

dyskinesias — abnormal involuntary twisting 

and writhing movements that can result from longterm use of high doses of levodopa. 

dystonia — involuntary muscle contractions that 

cause slow repetitive movements or abnormal postures.

neurotransmitters — chemicals which carry 

messages from one nerve cell, or neuron, to another.

pallidotomy — a surgical procedure in which a part 

of the brain called the globus pallidus is lesioned in 

order to improve symptoms of tremor, rigidity, and 

bradykinesia. 

parkinsonian gait — a characteristic way of 

walking that includes a tendency to lean forward; 

small, quick steps as if hurrying forward (called 

festination); and reduced swinging of the arms. 
49

parkinsonism — a term referring to a group of 

conditions that are characterized by four typical 

symptoms—tremor, rigidity, postural instability, 

and bradykinesia. 

“Parkinson’s-plus” — a group of diseases that 

includes corticobasal degeneration, progressive 

supranuclear palsy, and multiple system atrophy. 

These diseases cause symptoms like those of PD 

in addition to other symptoms. 

postural instability — impaired balance that 

causes a tendency to lean forward or backward 

and to fall easily. 

rigidity — a symptom of the disease in which 

muscles feel stiff and display resistance to movement 

even when another person tries to move the affected 

part of the body, such as an arm. 

substantia nigra — movement-control center in 

the brain where loss of dopamine-producing nerve 

cells triggers the symptoms of PD; substantia nigra 

means “black substance,” so called because the 

cells in this area are dark. 

thalamotomy — a procedure in which a portion 

of the brain’s thalamus is surgically destroyed, 

usually reducing tremors. 

tremor — shakiness or trembling, often in a hand, 

which in PD is usually most apparent when the 

affected part is at rest. 

wearing-off effect — the tendency, following 

long-term levodopa treatment, for each dose of the 

drug to be effective for shorter and shorter periods. 
50

Credits

Illustrations and photos:

Penn State Hershey Medical Center, Dr. Xuemei Huang Lab—Page 38

Bob Stockfield, for National Center for Complementary and Integrative 

Health—Page 42

Prepared by: 

Office of Communications and Public Liaison 

National Institute of Neurological Disorders and Stroke 

National Institutes of Health 

Bethesda, Maryland 20892

NIH Publication No. 15-139

December 2014

NIH . . . Turning Discovery Into Health