Neurodegenerative Diseases

Neurodegenerative disorders are primarily characterized by neuron loss. The most common NDs include Alzheimer’s disease, Parkinson’s disease, prion disease, amyotrophic lateral sclerosis (ALS—also known as Lou Gehrig’s disease), motor neuron disease, Huntington’s disease and spinal muscular atrophy (SMA).

Alzheimer’s disease is a brain disorder that slowly destroys memory and thinking skills, and eventually, the ability to carry out the simplest tasks. In most people with Alzheimer’s, symptoms first appear later in life. Estimates vary, but experts suggest that more than 6 million Americans, most of them age 65 or older, may have Alzheimer’s. Alzheimer’s is currently ranked as the seventh leading cause of death in the United States and is the most common cause of dementia among older adults.

Dementia is the loss of cognitive functioning—thinking, remembering and reasoning—and behavioral abilities to such an extent that it interferes with a person’s daily life and activities. Dementia ranges in severity from the mildest stage, when it is just beginning to affect a person’s functioning, to the most severe stage, when the person must depend completely on others for help with basic activities of daily living.

The causes of dementia can vary depending on the types of brain changes that may be taking place. Other forms of dementia include Lewy body dementia, frontotemporal disorders and vascular dementia. It is common for people to have mixed dementia—a combination of two or more types of dementia. For example, some people have both Alzheimer’s and vascular dementia.

Alzheimer’s disease is named after Dr. Alois Alzheimer. In 1906, Dr. Alzheimer noticed changes in the brain tissue of a woman who had died of an unusual mental illness. Her symptoms included memory loss, language problems and unpredictable behavior. After she died, he examined her brain and found many abnormal clumps (now called amyloid plaques) and tangled bundles of fibers (now called neurofibrillary, or tau, tangles).

These plaques and tangles in the brain are still considered some of the main features of Alzheimer’s. Another feature is the loss of connections between neurons in the brain. Neurons transmit messages between different parts of the brain, and from the brain to muscles and organs in the body.

Parkinson’s disease (PD) is movement disorder of the nervous system that gets worse over time. As nerve cells (neurons) in parts of the brain weaken, are damaged 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 symptoms progress, 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.

Prion diseases are transmissible, untreatable and fatal brain diseases of mammals. Their cause is highly unusual: The host’s normal prion protein can, for unknown reasons, malfunction and assemble into structured aggregates called prions that cause infectious brain disease. This process—which can be underway for years before symptoms appear—likely causes the most common form of prion disease in people, sporadic Creutzfeldt-Jakob disease (CJD). Other forms of human prion diseases include variant CJD, fatal familial insomnia, Gerstmann-Straussler-Scheinker syndrome and Kuru.

Amyotrophic lateral sclerosis (ALS) is a disease that affects the nerve cells that make muscles work in both the upper and lower parts of the body. Many people know ALS as Lou Gehrig’s disease, named after the famous baseball player who got the illness and had to retire in 1939 because of it. This disease makes the nerve cells stop working and die. The nerves lose the ability to trigger specific muscles, which causes the muscles to become weak and leads to paralysis.

Motor neuron disease (MND) is a rare brain and nerve condition that causes weakness that progressively worsens over time. Life expectancy is shortened with an MND diagnosis, though some continue to live with the condition for years. 

Huntington’s disease (HD), a neurodegenerative autosomal dominant disorder, is characterized by involuntary choreatic movements with cognitive and behavioral disturbances. HD is an inherited condition that causes progressive degeneration of neurons in the brain. 

Spinal muscular atrophy (SMA) is an inherited autosomal recessive disease that is characterized by progressive muscle weakness and reduced tone. SMA is a group of genetic neuromuscular disorders that affect the nerve cells that control voluntary muscles (motor neurons). The loss of motor neurons causes progressive muscle weakness and loss of movement due to muscle wasting, or atrophy. Many types of SMA mainly affect the muscles involved in walking, sitting, arm movement and head control. Breathing and swallowing may also become difficult as the disease progresses in many types of SMA. In some types of SMA, the loss of motor neurons makes it hard to control movement of the hands and feet.

Neurodegenerative diseases are often genetic, though they can also be caused by a tumor, stroke or the disease of alcoholism. Environmental exposure to toxins, chemicals and viruses may also be connected to the deterioration of nerve cells in the brain. Scientists continue to unravel the complex brain changes involved in Alzheimer’s.

Changes in the brain may begin a decade or more before symptoms appear. During this very early stage of Alzheimer’s, toxic changes are taking place in the brain, including abnormal buildups of proteins that form amyloid plaques and tau tangles. Previously healthy neurons stop functioning, lose connections with other neurons and die. Many other complex brain changes are thought to play a role in Alzheimer’s as well.

The damage initially appears to take place in the hippocampus and the entorhinal cortex, which are parts of the brain that are essential in forming memories. As more neurons die, additional parts of the brain are affected and begin to shrink. By the final stage of Alzheimer’s, damage is widespread and brain tissue has shrunk significantly.

No one knows what causes most cases of ALS. Scientists have been studying many factors that could be linked with ALS such as heredity and environmental exposures. Other scientists have looked at diet or injury. Although no cause has been found for most cases of ALS, a number of inherited factors have been found to cause familial ALS. In the future, scientists may find that many factors together cause ALS.

Health studies have not found definite environmental factors that are linked with ALS. Some studies suggested a possible link with exposure to heavy metals (e.g., lead and mercury). Other studies suggested a link with exposure to trace elements, solvents, radiation and agricultural chemicals. No confirmed link was found with infections, diet, physical activity and injury.

Motor neuron disease is caused by a problem with cells in the brain and nerves called motor neurons. These cells gradually stop working over time. It’s not known why this happens. Having a close relative with motor neuron disease, or a related condition called frontotemporal dementia, can sometimes mean you’re more likely to get it, but it does not run in families in most cases.

The precise cause of Parkinson’s disease (PD) is unknown, although some cases 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 genetics and exposure to one or more unknown environmental factors that trigger 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. The neurons in this area produce dopamine. Dopamine is the 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 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. People with PD also lose the nerve endings that produce the neurotransmitter norepinephrine—the main chemical messenger to the part of the nervous system that controls many autonomic functions of the body, such as pulse and blood pressure. The loss of norepinephrine might explain several of the non-motor features seen in PD, including fatigue and abnormalities of blood pressure regulation.

The protein alpha-synuclein: The affected brain cells of people with PD contain Lewy bodies, which are 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.

Genetics: Several genetic mutations are associated with PD, including the alpha-synuclein gene, and many more genes have been tentatively linked to the disorder. The same genes and proteins that are altered in inherited cases may also be altered in sporadic cases by environmental toxins or other factors.

Environment: Exposure to certain toxins has caused parkinsonian symptoms in rare circumstances (such as exposure to MPTP, an illicit drug, or in miners exposed to the metal manganese). Other still-unidentified environmental factors may also cause PD in genetically susceptible individuals.

Mitochondria: 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 stress–related 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.

Huntington’s disease (HD) is an inherited condition that causes progressive degeneration of neurons in the brain. It is caused by changes in the HTT gene and is inherited in an autosomal dominant manner. There is also a less common, early-onset form of HD which begins in childhood or adolescence. Similarly, spinal muscular atrophy (SMA) is caused by genetic changes and are inherited in an autosomal recessive manner.

Scientists recognize that the combination of a person’s genes and environment contributes to their risk of developing a neurodegenerative disease. For example, someone might have a gene that makes them more susceptible to Parkinson’s disease, but their environmental exposures can affect whether, when and how severely they are affected.

Critical research entails examining exposures that may have occurred before a disease diagnosis and understanding their effects.

Some people with memory problems have a condition called mild cognitive impairment (MCI). With MCI, people have more memory problems than normal for their age, but their symptoms do not interfere with their everyday lives. Movement difficulties and problems with the sense of smell have also been linked to MCI. Older people with MCI are at greater risk for developing Alzheimer’s, but not all of them do so.

People with Down syndrome also have a higher risk of developing Alzheimer’s earlier in life. Down syndrome results from having an extra chromosome 21, which carries the APP gene that produces the amyloid precursor protein. Too much of this protein leads to buildup of beta-amyloid plaques in the brain. Estimates suggest that 50 percent or more of people living with Down syndrome will develop Alzheimer’s, with symptoms appearing in their 50s and 60s.

Research suggests that a host of factors beyond genetics may play a role in the development and course of Alzheimer’s. There is a great deal of interest, for example, in the relationship between cognitive decline and vascular conditions, such as heart disease, stroke and high blood pressure, as well as metabolic diseases, such as diabetes and obesity. Ongoing research will help us understand whether and how reducing risk factors for these conditions may also reduce the risk of Alzheimer’s.

A nutritious diet, physical activity, social engagement and mentally stimulating pursuits have all been associated with helping people stay healthy as they age. These factors might also help reduce the risk of cognitive decline and Alzheimer’s. Researchers are testing some of these possibilities in clinical trials.

Screening for one potential degenerative disease biomarker, a protein called neurofilament light chain (NfL), is showing promising results for early detection. NfL is released when nerve cells are damaged, and elevated NfL concentrations are found in cerebrospinal fluid (CSF; a clear, colorless fluid that flows in and around the brain and spinal cord to help cushion them from injury and provide nutrients) in most neurodegenerative disorders. But CSF collection is an invasive procedure. This limits the use of CSF NfL for routine diagnosis. 

However, NfL concentrations in an individual’s blood correlate strongly with those found in CSF. This suggests that blood NfL could be a less invasive biomarker screening, and could potentially be used to detect neurodegenerative diseases. 

There are currently no specific tests to diagnose Parkinson’s disease (PD). The diagnosis is based on:

• Medical history and a neurological examination
• Blood and laboratory tests to rule out other disorders that may be causing the symptoms
• Brain scans to rule out other disorders. However, computed tomography (CT), and magnetic resonance imaging (MRI) brain scans of people with PD usually appear "normal" or "unremarkable."

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.

A healthy diet: At this time there are no specific vitamins, minerals or other nutrients that have any proven therapeutic value in PD. The National Institute of Neurological Disorders and Stroke (NINDS) and other components of the National Institutes of Health (NIH) are funding research to determine if caffeine, antioxidants and other dietary factors may be beneficial for preventing or treating PD. A 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 absorption of the drug levodopa.

Exercise: Exercise can help people with PD improve their mobility, flexibility and body strength. It also can improve well-being and balance, minimize gait problems, and strengthen certain muscles so that people can speak and swallow better. General physical activity, such as walking, gardening, swimming, calisthenics and using exercise machines, can have other benefits. People with PD should always check with their doctors before beginning a new exercise program.

Alternative approaches that are used by some individuals with PD include:

• A NINDS-funded clinical trial demonstrated the benefit of tai chi exercise compared to resistance or stretching exercises in people with PD
• Massage therapy to reduce muscle tension
• Yoga to increase stretching and flexibility
• Hypnosis acupuncture
• The Alexander Technique to optimize posture and muscle activity

Those concerned with developing degenerative diseases can practice healthy lifestyle choices including keeping a healthy weight through diet and exercise, having body antioxidant levels scanned, taking daily nutritional and genetic expression supplements, avoiding alcohol and getting enough sleep to prevent or delay diagnosis.

Disruptions in emotional, cognitive and social behavior are common in neurodegenerative disease. There are five symptoms that occur in neurodegenerative diseases, including anxiety, dysphoric mood, apathy, disinhibition and euphoric mood.

Neurodegenerative diseases typically have an onset in mid- to late life and are characterized by insidious onset and gradual decline. In the early stages of progression, each neurodegenerative disease shows signs of degeneration of motor, cognitive, behavioral and emotional symptoms.

Anxiety is a common symptom in multiple neurodegenerative diseases and commonly presents as worried appearance, fearfulness (e.g., fear of being left alone), tension, restlessness and fidgeting.

Symptoms of depression are also common in neurodegenerative disease. Although the depressive symptoms experienced by those with dementia are quite similar to those seen in depressed older adults who are cognitively normal, some symptoms (like irritability and social isolation) may be more common than others (like diminished interest in activities) in depressed individuals with dementia. Signs of depression include sadness, crying spells and hopelessness.

Apathy refers to a group of cognitive, behavioral and affective symptoms including lack of initiative and motivation, and lack of interest in pursuing goal-directed activities.

Memory problems are typically one of the first signs of cognitive impairment related to Alzheimer’s. Some people with memory problems have a condition called mild cognitive impairment (MCI). With MCI, people have more memory problems than normal for their age, but their symptoms do not interfere with their everyday lives. Movement difficulties and problems with the sense of smell have also been linked to MCI. Older people with MCI are at greater risk for developing Alzheimer’s, but not all of them do so. Some may even revert to normal cognition.

The first symptoms of Alzheimer’s vary from person to person. For many, decline in non-memory aspects of cognition, such as word finding, vision/spatial issues, and impaired reasoning or judgment may signal the very early stages of the disease. Researchers are studying biomarkers (biological signs of disease found in brain images, cerebrospinal fluid and blood) to detect early changes in the brains of people with MCI and in cognitively normal people who may be at greater risk for Alzheimer’s. More research is needed before these techniques can be used broadly and routinely to diagnose Alzheimer’s in a healthcare provider’s office.

Prion disease symptoms reflect the brain being destroyed and can range from memory loss and unstable movement to being unable to sleep or realize the need to eat. 

Early symptoms of ALS may be a feeling in the hands that makes it difficult to grip small items, such as a steering wheel; slurring of speech; stumbling; swallowing problems; muscle stiffness; worsening posture; and muscle control over time. Similarly, weakened muscles may be a symptom of motor neuron disease, as are breathing problems, delayed gross motor skills and limited mobility. 

Symptoms of Huntington’s disease include any combination of the following symptoms: 

• involuntary and random movements of the body
• cognitive decline
• change in sex drive—from one extreme to another
• abnormal eye movement
• loss of smell
• aggressive behavior (verbal or physical) or hostility
• restlessness and agitation
• apathy
• slow movement
• lack of physical coordination; clumsiness
• delusions
• difficulty walking, imbalance
• general weakness
• hallucinations
• obsessive or compulsive behaviors
• seizures
• increase of choking incidents 

The four primary symptoms of Parkinson’s disease (PD) are:

1. Tremor: Tremor (shaking) often begins in a hand, although sometimes a foot or the jaw is affected first. The tremor associated with PD has a characteristic rhythmic back-and-forth motion that may involve the thumb and forefinger and appear as “pill rolling.” It is most obvious when the hand is at rest or when a person is under stress. This tremor usually disappears during sleep or improves with a purposeful, intended movement.
2. Rigidity: Rigidity (muscle stiffness), 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 short, jerky movements known as “cogwheel” rigidity.
3. Bradykinesia: This is a slowing down of spontaneous and automatic movement that can be particularly frustrating because it may make simple tasks difficult. Activities once performed quickly and easily—such as washing or dressing—may take much longer. There is often a decrease in facial expressions (also known as "masked face").
4. Postural instability: Impaired balance and changes in posture can increase the risk of falls.

PD does not affect everyone the same way. 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, although symptoms are often less severe on one side than on the other.

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).

Other problems may accompany PD, such as:

• Depression: Some people lose their motivation and become dependent on family members.
• Emotional changes: Some people with PD become fearful and insecure, while others may become irritable or uncharacteristically pessimistic.
• Difficulty with swallowing and chewing: Problems with swallowing and chewing may occur 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. Getting adequate nutrition may be difficult.
• 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.
• Urinary problems or constipation: Bladder and bowel problems can occur due to the improper functioning of the autonomic nervous system, which is responsible for regulating smooth muscle activity.
• Skin problems: 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. 
• Sleep problems: Common sleep problems in PD 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 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 sleep issues. Many of these problems respond to specific therapies.
• Dementia or other cognitive problems: Some people with PD develop memory problems and slow thinking. Cognitive problems become more severe in the late stages of PD, and some people are diagnosed with Parkinson’s disease dementia (PDD). Memory, social judgment, language, reasoning or other mental skills may be affected.
• 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, which controls heart rate, blood pressure and other automatic functions in the body. The medications used to treat PD may also contribute.
• Muscle cramps and dystonia: The rigidity and lack of normal movement associated with PD often causes muscle cramps, especially in the legs and toes. 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 (a chemical in the brain that helps nerve cells communicate and is involved with movement).
• Pain: Muscles and joints may ache because of the rigidity and abnormal postures often associated with the disease.
• 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, which is trouble initiating or carrying out movement.
• 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.
• Hallucinations, delusions and other psychotic symptoms can be caused by the drugs prescribed for PD.

PD is the most common form of parkinsonism, which describes disorders of other causes that produce features and symptoms that closely resemble Parkinson’s disease. Many disorders can cause symptoms similar to those of PD:

• Multiple system atrophy (MSA) refers to a set of slowly progressive disorders that affect the central and autonomic nervous systems. The protein alpha-synuclein forms harmful filament-like aggregates in the supporting cells in the brain called oligodendroglia. 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. MSA with parkinsonian symptoms is sometimes referred to as MSA-P (or striatonigral degeneration).
• Lewy body dementia is associated with the same abnormal protein deposits (Lewy bodies) found in Parkinson’s disease but appears in 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 (vary) dramatically. Other symptoms may include visual hallucinations, psychiatric disturbances such as delusions and depression, and problems with cognition.
• Progressive supranuclear palsy (PSP) is a rare, progressive brain disorder caused by a gradual deterioration of cells in the brain stem. Symptoms may include problems with control of gait and balance (people often tend to fall early in the course of PSP), an inability to move the eyes, and alterations of mood and behavior, including depression and apathy as well as mild dementia. PSP is characterized by clumps of a protein called tau. 
• 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 include rigidity, impaired balance and problems with coordination. Other symptoms may include dystonia that affects one side of the body, 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). CBD also is characterized by deposits of the tau protein.

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.

Scientists recognize that the combination of a person’s genes and environment contributes to their risk of developing a neurodegenerative disease. For example, someone might have a gene that makes them more susceptible to Parkinson’s disease, but their environmental exposures can affect whether, when and how severely they are affected.

The most reliable tests used for diagnosing neurodegenerative diseases are neuroimaging techniques like single-photon emission computed tomography (SPECT) and positron emission tomography (PET). Molecular diagnostics also provides a powerful method to detect and diagnose various neurological diseases such as Alzheimer’s and Parkinson’s diseases. 

Specifically for Alzheimer’s disease, doctors use several methods and tools to help determine whether a person who is having memory problems has Alzheimer’s.

To diagnose Alzheimer’s, doctors may:

• Ask the person and a family member or friend questions about overall health, use of prescription and over-the-counter medicines, diet, past medical problems, ability to carry out daily activities, and changes in behavior and personality.
• Conduct tests of memory, problem solving, attention, counting and language.
• Order blood, urine, and other standard medical tests to help identify other possible causes of the problem.
• Administer tests to determine if depression or another mental health condition is causing or contributing to a person’s symptoms.
• Collect cerebrospinal fluid via a spinal tap or order blood tests to measure the levels of proteins associated with Alzheimer’s and related dementias.
• Perform brain scans, such as CT, MRI or PET (positron emission tomography), to support an Alzheimer’s diagnosis or to rule out other possible causes for symptoms.

These tests may be repeated to give doctors information about how the person’s memory and other cognitive functions are changing over time.

People with memory and thinking concerns should talk to their doctor to find out whether their symptoms are due to Alzheimer’s or to another cause, such as stroke, tumor, Parkinson’s disease, sleep disturbances, side effects of medication, an infection or another type of dementia. Some of these conditions may be treatable and, possibly, reversible.

If the diagnosis is Alzheimer’s, beginning treatment as early as possible in the disease process may help preserve daily functioning for a while. An early diagnosis also helps families plan for the future. They can take care of financial and legal matters, address potential safety issues, learn about living arrangements and develop support networks.

In addition, an early diagnosis provides people with more opportunities to participate in clinical trials or studies testing possible new treatments for Alzheimer’s.

There are currently no specific tests that diagnose PD. The diagnosis is based on:

• Medical history and a neurological examination
• Blood and laboratory tests to rule out other disorders that may be causing the symptoms
• Brain scans to rule out other disorders. However, computed tomography (CT) and magnetic resonance imaging (MRI) brain scans of people with PD usually appear "normal" or "unremarkable."

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.

No effective therapeutics to treat neurodegenerative diseases exist, despite significant attempts to find drugs that can reduce or rescue the debilitating symptoms of tauopathies such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, amyotrophic lateral sclerosis or Pick’s disease.

Treatment is limited to symptomatic relief—for example, using dopaminergic treatment (which regulates levels of the dopamine, a neurotransmitter) for Parkinson’s and other movement disorders, antipsychotic drugs for dementia, anti-inflammatory and analgesic prescriptions (painkillers) for neuronal infections, and cholinesterase (an enzyme occurring at neuromuscular junctions) for cognitive disorders.

Currently, there is no cure for Parkinson’s disease (PD), but medications or surgery can often provide improvement in the motor symptoms.

Medications for PD fall into three categories:

1. Drugs that increase the level of dopamine in the brain. The most common drugs for PD are dopamine precursors—substances like levodopa that cross the blood-brain barrier and are then changed into dopamine. Other drugs mimic dopamine or prevent or slow its breakdown.
2. Drugs that affect other neurotransmitters in the body 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.
3. Medications that help control the non-motor symptoms of the disease, or the symptoms that don’t affect movement. For example, people with PD-related depression may be prescribed antidepressants.

Symptoms may significantly improve at first with medication but can reappear over time as PD worsens and drugs become less effective.

Levodopa-carbidopa: The cornerstone of PD therapy is the drug levodopa (also known as 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, which is a protective lining of cells inside blood vessels that regulate the transport of oxygen, glucose and other substances in the brain.

People are given levodopa combined with another substance called carbidopa. When added to levodopa, carbidopa prevents the 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. People may need to increase their dose of levodopa gradually for maximum benefit. Levodopa can reduce the symptoms of PD, but it does not replace lost nerve cells or stop its progression.

Initial side effects of levodopa-carbidopa may include:

• Nausea
• Low blood pressure
• Restlessness
• Drowsiness or sudden sleep 

Side effects of long-term or extended use of levodopa may include:

• Hallucinations and psychosis
• Dyskinesia, or involuntary movements such as mild to severe twisting and writhing

Later in the course of the disease, 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 this is to take levodopa more often and in smaller amounts. People with PD should never stop taking levodopa without their physician’s input, because rapidly withdrawing the drug can have potentially serious side effects. 

Dopamine agonists: These mimic the role of dopamine in the brain and 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. Dopamine agonist drugs include apomorphine, pramipexole, ropinirole and rotigotine. 

MAO-B inhibitors: These drugs block or reduce the activity of 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. These medications include selegiline and rasagiline. Studies supported by the National Institute of Neurological Disorders and Stroke (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. The drug rasagiline is used in treating the motor symptoms of PD with or without levodopa.

COMT inhibitors: COMT stands for catechol-O-methyltransferase and is another enzyme that breaks down dopamine. The drugs entacapone, opicapone 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. Side effects may include diarrhea, 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 can be prescribed alone in the early stages of the disease and can 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 particularly effective for tremor associated with PD. 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 right. Even then, symptoms may not be completely alleviated.

Medications to treat motor symptoms of PD:
 

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.

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 drug-induced 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 method using focused ultrasound from outside the head is being tested because it creates lesions without the need for surgery.

Deep Brain Stimulation

Deep brain stimulation (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. (The signal can be turned off using the wand.) 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. DBS is approved by the U.S. Food and Drug Administration (FDA) and is widely used as a treatment for PD.

• 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.
• DBS does not stop PD from progressing, and some problems may gradually return. 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.
• DBS is generally appropriate for people with levodopa-responsive PD who have developed dyskinesias or other disabling “off” symptoms despite drug therapy. 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.

Complementary & Supportive Therapies

A wide variety of complementary and supportive therapies may be used for PD, including:

A healthy diet: At this time there are no specific vitamins, minerals or other nutrients that have any proven therapeutic value in PD. The National Institute of Neurological Disorders and Stroke (NINDS) and other components of the NIH are funding research to determine if caffeine, antioxidants and other dietary factors may be beneficial for preventing or treating PD. A 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.

Exercise: Exercise can help people with PD improve their mobility, flexibility and body strength. It also can improve well-being and balance, minimize gait problems and strengthen certain muscles so that people can speak and swallow better. General physical activity, such as walking, gardening, swimming, calisthenics and using exercise machines, can have other benefits. People with PD should always check with their doctors before beginning a new exercise program.

Alternative approaches that are used by some individuals with PD include:

• Tai chi (a NINDS-funded clinical trial demonstrated the benefit of tai chi exercise compared to resistance or stretching exercises in people with PD)
• Massage therapy to reduce muscle tension
• Yoga to increase stretching and flexibility
• Hypnosis acupuncture
• The Alexander Technique to optimize posture and muscle activity

Treatment is limited to symptomatic relief—for example, using dopaminergic treatment (which regulates levels of the dopamine—a neurotransmitter) for Parkinson’s and other movement disorders, antipsychotic drugs for dementia, anti-inflammatory and analgesic prescriptions (painkillers) for neuronal infections and cholinesterase (an enzyme occurring at neuromuscular junctions) for cognitive disorders.

However, following a neurodegenerative disease diagnosis, people can live for many years if they manage their symptoms effectively. Quality of life is improved with a healthy lifestyle, regular exercise and healthy eating.

Caring for a person with Alzheimer’s can have significant physical, emotional and financial costs. The demands of day-to-day care, changes in family roles, and decisions about placement in a care facility can be difficult. NIA supports efforts to evaluate programs, strategies, approaches and other research to improve the quality of care and life for those living with dementia and their caregivers.

Becoming well informed about the disease is one important long-term strategy. Programs that teach families about the various stages of Alzheimer’s and about ways to deal with difficult behaviors and other caregiving challenges can help.

Good coping skills, a strong support network and respite care are other things that may help caregivers handle the stress of caring for a loved one with Alzheimer’s. For example, staying physically active provides physical and emotional benefits.

Some caregivers have found that joining a support group is a critical lifeline. These support groups enable caregivers to find respite, express concerns, share experiences, get tips and receive emotional comfort. Many organizations sponsor in-person and online support groups, including groups for people with early-stage Alzheimer’s and their families.

There’s no cure for motor neuron disease, but treatment can help reduce the impact the symptoms have on your life. 

Treatments may include:

• Highly specialized clinics, typically involving a specialist nurse and occupational therapy to help make everyday tasks easier
• Physiotherapy and exercises to maintain strength and reduce stiffness
• Working with a speech and language therapist
• Working with a dietitian about diet 
• A medicine called riluzole that can slightly slow down the progression of the condition, and other medicines to relieve muscle stiffness and help with saliva problems
• Emotional support for you and your caregiver

While Parkinson’s disease (PD) usually progresses slowly, daily routines may eventually 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 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. 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 proactive role in maintaining 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.

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.

Because PD is a slow, progressive disorder, it is not possible to predict what course the disease will take for an individual person.

For all neurodegenerative diseases, consider participating in a clinical trial so clinicians and scientists can learn more about your diagnosis and related disorders. Clinical research uses human volunteers to help researchers learn more about a disorder and perhaps find better ways to safely detect, treat or prevent disease.

All types of volunteers are needed—those who are healthy or may have an illness or disease—of all different ages, sexes, races and ethnicities to ensure that study results apply to as many people as possible, and that treatments will be safe and effective for everyone who will use them.