Dementia with Lewy bodies is a nervous system disorder characterized by a decline in intellectual function (dementia), a group of movement problems known as parkinsonism, visual hallucinations, sudden changes (fluctuations) in behavior and intellectual ability, and acting out dreams while asleep (REM sleep behavior disorder). This condition typically affects older adults, most often developing between ages 50 and 85. The life expectancy of individuals with dementia with Lewy bodies varies; people typically survive about 5 to 7 years after they are diagnosed.

REM sleep behavior disorder may be the first sign of dementia with Lewy bodies. It can occur years before other symptoms appear. Individuals with REM sleep behavior disorder act out their dreams, talking and moving in their sleep when they should be still. This behavior becomes less pronounced as dementia with Lewy bodies worsens and additional features develop.

Dementia is often the second major feature to develop in dementia with Lewy bodies. Initially, this intellectual decline may be mild or seem to come and go. In this condition, dementia often leads to impaired ability to perform visual-spatial tasks such as assembling puzzles. Affected individuals may also have poor problem-solving skills (executive functioning), speech difficulties, and reduced inhibitions. Problems with memory typically do not occur until later.

Most people with dementia with Lewy bodies experience visual hallucinations, which often involve people or animals. Fluctuations in behavior and thought processes (cognition) include sudden changes in attention, unintelligible speech, and brief episodes of altered consciousness that may appear as staring spells.

Parkinsonism is usually the last major feature to develop in people with dementia with Lewy bodies, although it can appear earlier in some individuals. The movement problems typically include tremors, rigidity, unusually slow movement (bradykinesia), and impaired balance and coordination (postural instability). Affected individuals may require walking aids or wheelchair assistance over time.

Individuals with dementia with Lewy bodies may also experience a sharp drop in blood pressure upon standing (orthostatic hypotension), fainting episodes (syncope), reduced sense of smell, increased saliva production and drooling, difficulty controlling the flow of urine (incontinence), or constipation.

Lewy bodies are named for Dr. Friederich Lewy, a German neurologist. In 1912, he discovered abnormal protein deposits that disrupt the brain's normal functioning in people with Parkinson's disease. These abnormal deposits are now called "Lewy bodies."

Lewy bodies are made of a protein called alpha-synuclein. In the healthy brain, alpha-synuclein plays a number of important roles in neurons (nerve cells) in the brain, especially at synapses, where brain cells communicate with each other. In Lewy body dementia, alpha-synuclein forms into clumps inside neurons, starting in areas of the brain that control aspects of memory and movement. This process causes neurons to work less effectively and, eventually, to die. The activities of certain brain chemicals are also affected. The result is widespread damage to specific brain regions and a decline in abilities affected by those brain regions.

Lewy bodies affect several different brain regions in Lewy body dementia:

• The cerebral cortex, which controls many functions, including information processing, perception, thought, and language
• The limbic cortex, which plays a major role in emotions and behavior
• The hippocampus, which is essential to forming new memories
• The midbrain and basal ganglia, which are involved in movement
• The brain stem, which is important in regulating sleep and maintaining alertness
• Brain regions important in recognizing smells (olfactory pathways)

Dementia with Lewy bodies is estimated to affect 1.4 million people in the United States. It accounts for about 5 percent of all dementia cases in older individuals and is the second most common dementia after Alzheimer's disease.

What is dementia with Lewy bodies?

Dementia with Lewy bodies (DLB) is one of the most common types of progressive dementia. The central features of DLB include progressive cognitive decline, “fluctuations” in alertness and attention, visual hallucinations, and parkinsonian motor symptoms, such as slowness of movement, difficulty walking, or rigidity. People may also suffer from depression. The symptoms of DLB are caused by the build-up of Lewy bodies – accumulated bits of alpha-synuclein protein -- inside the nuclei of neurons in areas of the brain that control particular aspects of memory and motor control. Researchers don’t know exactly why alpha-synuclein accumulates into Lewy bodies or how Lewy bodies cause the symptoms of DLB, but they do know that alpha-synuclein accumulation is also linked to Parkinson's disease, multiple system atrophy, and several other disorders, which are referred to as the "synucleinopathies." The similarity of symptoms between DLB and Parkinson’s disease, and between DLB and Alzheimer’s disease, can often make it difficult for a doctor to make a definitive diagnosis. In addition, Lewy bodies are often also found in the brains of people with Parkinson's and Alzheimer’s diseases. These findings suggest that either DLB is related to these other causes of dementia or that an individual can have both diseases at the same time. DLB usually occurs sporadically, in people with no known family history of the disease. However, rare familial cases have occasionally been reported.

Is there any treatment?

There is no cure for DLB. Treatments are aimed at controlling the cognitive, psychiatric, and motor symptoms of the disorder. Acetylcholinesterase inhibitors, such as donepezil and rivastigmine, are primarily used to treat the cognitive symptoms of DLB, but they may also be of some benefit in reducing the psychiatric and motor symptoms. Doctors tend to avoid prescribing antipsychotics for hallucinatory symptoms of DLB because of the risk that neuroleptic sensitivity could worsen the motor symptoms. Some individuals with DLB may benefit from the use of levodopa for their rigidity and loss of spontaneous movement.

What is the prognosis?

Like Alzheimer’s disease and Parkinson’s disease, DLB is a neurodegenerative disorder that results in progressive intellectual and functional deterioration. There are no known therapies to stop or slow the progression of DLB. Average survival after the time of diagnosis is similar to that in Alzheimer’s disease, about 8 years, with progressively increasing disability.

Mutations in genes known as SNCA and SNCB can cause dementia with Lewy bodies. The SNCA and SNCB genes provide instructions for making proteins, called alpha-synuclein and beta-synuclein, respectively, that are found primarily in the brain. Alpha-synuclein plays a role in communication between nerve cells (neurons), helping to regulate the release of chemical messengers (neurotransmitters). Beta-synuclein is likely involved in a process that allows neurons to change and adapt over time, which is necessary for learning and memory. Beta-synuclein may also prevent harmful accumulation of alpha-synuclein in neurons.

Mutations in another gene called GBA or a certain version of a gene called APOE increase the risk of developing the condition, but are not a direct cause. The enzyme produced from the GBA gene is found throughout the body in cell structures called lysosomes that digest and recycle proteins and other materials that are no longer needed. The APOE gene provides instructions for making a protein, called apolipoprotein E, which packages cholesterol and other fats and carries them through the bloodstream.

Changes in these four genes can lead to the formation of Lewy bodies, which are clusters of alpha-synuclein protein. SNCA gene mutations result in misshapen alpha-synuclein proteins that cluster together (aggregate). SNCB gene mutations lead to the production of an altered beta-synuclein protein that allows accumulation of alpha-synuclein. GBA gene mutations are thought to disrupt the normal function of lysosomes. Research suggests that malfunctioning lysosomes impair the breakdown of alpha-synuclein, increasing the risk of its accumulation and the formation of Lewy bodies. There are multiple versions of the APOE gene, one version, called the e4 allele, seems to increase an individual's risk for developing dementia with Lewy bodies, although the mechanism is unclear. It is thought that the apolipoprotein E produced from the e4 allele of the APOE gene may disrupt the transport of alpha-synuclein into and out of cells, leading to its accumulation.

In dementia with Lewy bodies, alpha-synuclein clusters accumulate inside and outside of neurons throughout the brain where they impair cell function and ultimately cause cell death. Neurons that produce the neurotransmitter dopamine seem to be particularly vulnerable to Lewy bodies. Dopamine has many important functions, including playing complex roles in cognition, motivation, behavior, and control of movement. Over time, the loss of dopamine-producing neurons can increasingly impair intellectual and motor function and the regulation of emotions, resulting in the signs and symptoms of dementia with Lewy bodies.

Normal Function

The APOE gene provides instructions for making a protein called apolipoprotein E. This protein combines with fats (lipids) in the body to form molecules called lipoproteins. Lipoproteins are responsible for packaging cholesterol and other fats and carrying them through the bloodstream. Maintaining normal levels of cholesterol is essential for the prevention of disorders that affect the heart and blood vessels (cardiovascular diseases), including heart attack and stroke.

There are at least three slightly different versions (alleles) of the APOE gene. The major alleles are called e2, e3, and e4. The most common allele is e3, which is found in more than half of the general population.

Health Conditions Related to Genetic Changes

Alzheimer's disease

The e4 version of the APOE gene increases an individual's risk for developing late-onset Alzheimer's disease. Alzheimer's disease is a degenerative disease of the brain that causes dementia, which is a gradual loss of memory, judgment, and ability to function. The late-onset form of the condition occurs in people older than age 65. People who inherit one copy of the APOE e4 allele have an increased chance of developing the disease; those who inherit two copies of the allele are at even greater risk. The APOE e4 allele may also be associated with an earlier onset of memory loss and other symptoms compared to individuals with Alzheimer's disease who do not have this allele.

It is not known how the APOE e4 allele is related to the risk of Alzheimer's disease. However, researchers have found that this allele is associated with an increased number of protein clumps, called amyloid plaques, in the brain tissue of affected people. A buildup of amyloid plaques may lead to the death of nerve cells (neurons) and the progressive signs and symptoms of Alzheimer's disease.

It is important to note that people with the APOE e4 allele inherit an increased risk of developing Alzheimer's disease, not the disease itself. Not all people with Alzheimer's disease have the APOE e4 allele, and not all people who have this allele will develop the disease.

Age-related hearing loss

MedlinePlus Genetics provides information about Age-related hearing loss

Age-related macular degeneration

MedlinePlus Genetics provides information about Age-related macular degeneration

Dementia with Lewy bodies

The e4 version of the APOE gene can increase the risk of developing a form of dementia called dementia with Lewy bodies; however, some people with the APOE e4 allele never develop this condition. Dementia with Lewy bodies is characterized by intellectual decline; visual hallucinations; sudden changes in attention and mood; and movement problems characteristic of Parkinson's disease such as rigidity of limbs, tremors, and impaired balance and coordination.

People who inherit one copy of the APOE e4 allele have an increased chance of developing dementia with Lewy bodies. It is unclear how the APOE e4 allele contributes to the development of this condition. It is thought that the apolipoprotein E produced from the e4 allele of the APOE gene may disrupt the transport of a protein called alpha-synuclein into and out of cells. When alpha-synuclein is trapped inside or outside of cells, it accumulates in clusters, creating Lewy bodies. Accumulation of these clusters throughout the brain impairs neuron function and ultimately causes cell death. Over time, the loss of neurons increasingly impairs intellectual and motor function and the regulation of emotions, resulting in the signs and symptoms of dementia with Lewy bodies.

It is unclear why some people with the APOE e4 allele develop Alzheimer's disease while others develop dementia with Lewy bodies.

Other disorders

Variants of apolipoprotein E have been studied extensively as risk factors for many different conditions. For example, APOE alleles have been shown to influence the risk of cardiovascular diseases. People who carry at least one copy of the APOE e4 allele have an increased chance of developing atherosclerosis, which is an accumulation of fatty deposits and scar-like tissue in the lining of the arteries. This progressive narrowing of the arteries increases the risk of heart attack and stroke.

The APOE e2 allele has been shown to greatly increase the risk of a rare condition called hyperlipoproteinemia type III. Most people with this disorder have two copies of the APOE e2 allele, leading researchers to conclude that the e2 allele plays a critical role in the development of the condition. Hyperlipoproteinemia type III is characterized by increased blood levels of cholesterol, certain fats called triglycerides, and molecules called beta-very low-density lipoproteins (beta-VLDLs), which carry cholesterol and lipoproteins in the bloodstream. A buildup of cholesterol and other fatty materials can lead to the formation of small, yellow skin growths called xanthomas and the development of atherosclerosis.

Other Names for This Gene

• Apo-E
• APOE_HUMAN
• Apolipoproteins E

Genomic Location

Normal Function

The GBA gene provides instructions for making an enzyme called beta-glucocerebrosidase. This enzyme is active in lysosomes, which are structures inside cells that act as recycling centers. Lysosomes use digestive enzymes to break down toxic substances, digest bacteria that invade the cell, and recycle worn-out cell components. Based on these functions, enzymes in the lysosome are sometimes called housekeeping enzymes. Beta-glucocerebrosidase is a housekeeping enzyme that helps break down a large molecule called glucocerebroside into a sugar (glucose) and a simpler fat molecule (ceramide). Glucocerebroside is a component of the membrane that surrounds cells. It gets broken down by beta-glucocerebrosidase when cells die, and the components are reused as new cells are formed.

Health Conditions Related to Genetic Changes

Gaucher disease

More than 380 mutations in the GBA gene have been identified in people with Gaucher disease, a disorder with varied features that affect many parts of the body. Affected individuals can have enlargement of the liver and spleen (hepatosplenomegaly), blood cell abnormalities, and rarely, severe neurological problems. The mutations occur in both copies of the gene in each cell. Most of the GBA gene mutations responsible for Gaucher disease change single protein building blocks (amino acids) in beta-glucocerebrosidase, altering the structure of the enzyme and preventing it from working normally. Other mutations delete or insert genetic material in the GBA gene or lead to the production of an abnormally short, nonfunctional version of the enzyme.

Mutations in the GBA gene greatly reduce or eliminate the activity of beta-glucocerebrosidase in cells. As a result, glucocerebroside is not broken down properly. This molecule and related substances can build up in white blood cells called macrophages in the spleen, liver, bone marrow, and other organs. The abnormal accumulation and storage of these substances damages tissues and organs, causing the characteristic features of Gaucher disease.

Parkinson's disease

Changes in the GBA gene are also associated with Parkinson's disease and parkinsonism, which are similar disorders that affect movement. Characteristic features include tremors and impaired balance and coordination (postural instability). People with Gaucher disease (described above) have mutations in both copies of the GBA gene in each cell, while those with a mutation in just one copy of the gene are called carriers. People with Gaucher disease and people who are carriers of a GBA gene mutation have an increased risk of developing Parkinson's disease or parkinsonism.

Symptoms of Parkinson's disease and parkinsonism result from the loss of nerve cells (neurons) that produce dopamine. Dopamine is a chemical messenger that transmits signals within the brain to produce smooth physical movements. It remains unclear how GBA gene mutations are related to these disorders. Studies suggest that changes in this gene may contribute to the faulty breakdown of toxic substances in neurons by impairing the function of lysosomes. Alternatively, the changes may increase the formation of abnormal protein deposits. As a result, toxic substances or protein deposits could accumulate and kill dopamine-producing neurons, leading to abnormal movements and balance problems.

Dementia with Lewy bodies

GBA gene mutations can increase the risk of developing dementia with Lewy bodies; however, some people with a mutation in the GBA gene never develop this condition. Dementia with Lewy bodies is characterized by intellectual decline (dementia); visual hallucinations; sudden changes in attention and mood; and movement problems characteristic of Parkinson's disease (described above) such as rigidity of limbs, tremors, and impaired balance and coordination.

Mutations in one copy of the GBA gene increase the risk of developing dementia with Lewy bodies. These mutations result in the production of an altered beta-glucocerebrosidase enzyme. This abnormal enzyme may interfere with the function of lysosomes and the normal breakdown of a protein called alpha-synuclein, which increases the risk that these proteins accumulate and form Lewy bodies. Accumulation of these protein clusters throughout the brain impairs neuron function and ultimately causes cell death. Over time, the loss of neurons increasingly impairs intellectual and motor function and the regulation of emotions, resulting in the signs and symptoms of dementia with Lewy bodies.

Other Names for This Gene

• acid beta-glucosidase
• algucerase
• beta-D-glucosyl-N-acylsphingosine glucohydrolase
• beta-glucocerebrosidase
• GBA1
• GLCM_HUMAN
• GLUC
• glucocerebrosidase
• glucocerebroside beta-glucosidase
• glucosidase, beta, acid
• glucosidase, beta; acid (includes glucosylceramidase)
• glucosphingosine glucosylhydrolase
• glucosylceramide beta-glucosidase
• imiglucerase

Genomic Location

Normal Function

The SNCA gene provides instructions for making a small protein called alpha-synuclein. Alpha-synuclein is abundant in the brain, and smaller amounts are found in the heart, muscles, and other tissues. In the brain, alpha-synuclein is found mainly at the tips of nerve cells (neurons) in specialized structures called presynaptic terminals. Presynaptic terminals release chemical messengers, called neurotransmitters, from compartments known as synaptic vesicles. The release of neurotransmitters relays signals between neurons and is critical for normal brain function.

Although the function of alpha-synuclein is not well understood, studies suggest that it plays an important role in maintaining an adequate supply of synaptic vesicles in presynaptic terminals. It may also help regulate the release of dopamine, a neurotransmitter that is critical for controlling the start and stop of voluntary and involuntary movements. Alpha-synuclein may also play a role in the movement of structures called microtubules that help cells maintain their shape.

Health Conditions Related to Genetic Changes

Multiple system atrophy

Several common variations in the SNCA gene have been found to increase the risk of multiple system atrophy, a progressive brain disorder that affects movement and balance and disrupts the function of the autonomic nervous system. The autonomic nervous system controls actions that are mostly involuntary, such as regulation of blood pressure.

The identified gene variations each change a single DNA building block (nucleotide) in the SNCA gene. Researchers are working to determine whether these changes alter the function of alpha-synuclein and how they influence the risk of developing multiple system atrophy. Variations in the SNCA gene appear to affect disease risk in people of European descent; however, studies suggest that changes in this gene are not associated with multiple system atrophy in the Chinese population or in South Koreans. It is unclear whether SNCA gene variations are a risk factor for this condition in people of other geographic and ethnic backgrounds.

Dementia with Lewy bodies

At least six mutations in the SNCA gene have been found to cause dementia with Lewy bodies. This condition is characterized by intellectual decline (dementia); visual hallucinations; sudden changes in attention and mood; and movement problems characteristic of Parkinson's disease (described below) such as rigidity of limbs, tremors, and impaired balance and coordination. A characteristic feature of this condition is Lewy bodies, which are abnormal clusters of alpha-synuclein protein in the brain. Lewy bodies also occur in Parkinson's disease, but they tend to be more widespread in the brain in dementia with Lewy bodies.

In dementia with Lewy bodies, SNCA gene mutations lead to the production of an alpha-synuclein protein with an abnormal shape. The misshapen proteins cluster together, forming the main component of Lewy bodies. These protein clusters are present throughout the brain where they impair neuron function and ultimately cause cell death. Over time, the loss of neurons increasingly impairs intellectual and motor function and the regulation of emotions, resulting in the signs and symptoms of dementia with Lewy bodies.

Parkinson's disease

At least 30 mutations in the SNCA gene have been found to cause Parkinson's disease, a condition characterized by progressive problems with movement and balance. SNCA gene mutations are associated with the early-onset form of the disorder, which typically appears before age 50. Other variations in the SNCA gene have been found to increase the risk of developing Parkinson's disease, although they do not appear to be a direct cause of the disease.

Researchers have described two types of alterations of the SNCA gene in people with Parkinson's disease. One type changes single protein building blocks (amino acids) used to make alpha-synuclein. In some cases, the amino acid alanine is replaced with the amino acid threonine at protein position 53 (written as Ala53Thr or A53T) or with the amino acid proline at position 30 (written as Ala30Pro or A30P). These alterations cause the alpha-synuclein protein to take on an incorrect 3-dimensional shape (misfold). In the other type of alteration, one of the two SNCA genes in each cell is inappropriately duplicated or triplicated. The extra copies of the SNCA gene lead to an excess of alpha-synuclein protein.

It is unclear how alterations in the SNCA gene cause Parkinson's disease. This condition involves the selective death or impairment of neurons that produce dopamine. Misfolded or excess alpha-synuclein proteins may cluster together to form Lewy bodies and impair the function of these neurons in specific regions of the brain. Lewy bodies may disrupt the regulation of dopamine, which allows dopamine to accumulate to toxic levels and eventually kill neurons. Researchers also suspect that Lewy bodies stall or shut down the cell machinery that removes unneeded proteins. As a result, unneeded proteins may clog neurons and impair their functions. Symptoms of Parkinson's disease appear when dopamine-producing neurons become impaired or die. The loss of these cells weakens communication between the brain and muscles, and ultimately the brain becomes unable to control muscle movement. The presence of Lewy bodies in a region of the brain called the substantia nigra, which controls balance and movement, are a characteristic feature of Parkinson's disease.

Other Names for This Gene

• alpha-synuclein
• NACP
• nonA-beta component of AD amyloid
• PARK1
• PARK4
• PD1
• synuclein, alpha (non A4 component of amyloid precursor)
• SYUA_HUMAN

Genomic Location

Normal Function

The SNCB gene provides instructions for making a protein called beta-synuclein. The exact function of this protein is unknown, but it is likely involved in a process called synaptic plasticity. Synaptic plasticity is the ability of the connections between nerve cells (called synapses) to change and adapt over time in response to experience. This process is critical for learning and memory. Beta-synuclein may also prevent harmful accumulation of a similar protein called alpha-synuclein in nerve cells (neurons).

Health Conditions Related to Genetic Changes

Dementia with Lewy bodies

At least two mutations in the SNCB gene have been found to cause dementia with Lewy bodies. This condition is characterized by intellectual decline (dementia); visual hallucinations; sudden changes in attention and mood; and movement problems such as rigidity of limbs, tremors, and impaired balance and coordination.

SNCB gene mutations lead to the production of a protein with impaired function. It is thought that this altered protein may not be able to prevent alpha-synuclein accumulation. A decrease in functional beta-synuclein likely results in alpha-synuclein accumulation and the formation of Lewy bodies. These abnormal protein clusters are present throughout the brain, where they impair neuron function and ultimately cause cell death. Over time, the loss of neurons increasingly impairs intellectual and motor function and the regulation of emotions, resulting in the signs and symptoms of dementia with Lewy bodies.

Other Names for This Gene

• beta-synuclein

Genomic Location

When dementia with Lewy bodies is caused by SNCA or SNCB gene mutations, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In these cases, an affected person usually has one parent with the condition.

People with a mutation in one copy of the GBA gene or one copy of the APOE e4 allele inherit an increased risk of developing dementia with Lewy bodies, not the condition itself. Some people with these genetic variants never develop dementia with Lewy bodies. This increased risk is inherited in an autosomal dominant pattern.

People with LBD may not have every LBD symptom, and the severity of symptoms can vary greatly from person to person. Throughout the course of the disease, any sudden or major change in functional ability or behavior should be reported to a doctor.

The most common symptoms include changes in cognition, movement, sleep, and behavior.

Cognitive Symptoms

LBD causes changes in thinking abilities. These changes may include:

• Dementia—Severe loss of thinking abilities that interferes with a person’s capacity to perform daily activities. Dementia is a primary symptom in LBD and usually includes trouble with visual and spatial abilities (judging distance and depth or misidentifying objects), planning, multitasking, problem solving, and reasoning. Memory problems may not be evident at first but often arise as LBD progresses. Dementia can also include changes in mood and behavior, poor judgment, loss of initiative, confusion about time and place, and difficulty with language and numbers.

• Cognitive fluctuations— Unpredictable changes in concentration, attention, alertness, and wakefulness from day to day and sometimes throughout the day. A person with LBD may stare into space for periods of time, seem drowsy and lethargic, or sleep for several hours during the day despite getting enough sleep the night before. His or her flow of ideas may be disorganized, unclear, or illogical at times. The person may seem better one day, then worse the next day. These cognitive fluctuations are common in LBD but are not always easy for a doctor to identify.

• Hallucinations— Seeing or hearing things that are not present. Visual hallucinations occur in up to 80 percent of people with LBD, often early on. They are typically realistic and detailed, such as images of children or animals. Auditory hallucinations are less common than visual ones but may also occur. Hallucinations that are not disruptive may not require treatment. However, if they are frightening or dangerous (for example, if the person attempts to fight a perceived intruder), then a doctor may prescribe medication.

Movement Symptoms

Some people with LBD may not experience significant movement problems for several years. Others may have them early on. At first, signs of movement problems, such as a change in handwriting, may be very mild and thus overlooked. Parkinsonism is seen early on in Parkinson’s disease dementia but can also develop later on in dementia with Lewy bodies. Specific signs of parkinsonism may include:

• muscle rigidity or stiffness
• shuffling gait, slow movement, or frozen stance
• tremor or shaking, most commonly at rest
• balance problems and falls
• stooped posture
• loss of coordination
• smaller handwriting than was usual for the person
• reduced facial expression
• difficulty swallowing
• a weak voice

Sleep Disorders

Sleep disorders are common in people with LBD but are often undiagnosed. A sleep specialist can play an important role on a treatment team, helping to diagnose and treat sleep disorders. Sleep-related disorders seen in people with

LBD may include:

• REM sleep behavior disorder—A condition in which a person seems to act out dreams. It may include vivid dreaming, talking in one’s sleep, violent movements, or falling out of bed. Sometimes only the bed partner of the person with LBD is aware of these symptoms. REM sleep behavior disorder appears in some people years before other LBD symptoms.
• Excessive daytime sleepiness—Sleeping 2 or more hours during the day.
• Insomnia—Difficulty falling or staying asleep, or waking up too early.
• Restless leg syndrome—A condition in which a person, while resting, feels the urge to move his or her legs to stop unpleasant or unusual sensations. Walking or moving usually relieves the discomfort.

Behavioral and Mood Symptoms

Changes in behavior and mood are possible in LBD. These changes may include:

• Depression—A persistent feeling of sadness, inability to enjoy activities, or trouble with sleeping, eating, and other normal activities.
• Apathy—A lack of interest in normal daily activities or events; less social interaction.
• Anxiety—Intense apprehension, uncertainty, or fear about a future event or situation. A person may ask the same questions over and over or be angry or fearful when a loved one is not present.
• Agitation—Restlessness, as seen by pacing, hand wringing, an inability to get settled, constant repeating of words or phrases, or irritability.
• Delusions—Strongly held false beliefs or opinions not based on evidence. For example, a person may think his or her spouse is having
  an affair or that relatives long dead are still living. Another delusion that may be seen in people with LBD is Capgras syndrome, in which the person believes a relative or friend has been replaced by an imposter.
• Paranoia—An extreme, irrational distrust of others, such as suspicion that people are taking or hiding things.

Other LBD Symptoms

People with LBD can also experience significant changes in the part of the nervous system that regulates automatic functions such as those of the heart, glands, and muscles. The person may have:

• changes in body temperature
• problems with blood pressure
• dizziness
• fainting
• frequent falls
• sensitivity to heat and cold
• sexual dysfunction
• urinary incontinence
• constipation
• a poor sense of smell

It’s important to know which type of LBD a person has, both to tailor treatment to particular symptoms and to understand how the disease will likely progress. Clinicians and researchers use the “1-year rule” to diagnose which form of LBD a person has. If cognitive symptoms appear within a year of movement problems, the diagnosis is dementia with Lewy bodies. If cognitive problems develop more than a year after the onset of movement problems, the diagnosis is Parkinson’s disease dementia.

Regardless of the initial symptoms, over time people with LBD often develop similar symptoms due to the presence of Lewy bodies in the brain. But there are some differences. For example, dementia with Lewy bodies may progress more quickly than Parkinson’s disease dementia.

Dementia with Lewy bodies is often hard to diagnose because its early symptoms may resemble those of Alzheimer’s, Parkinson’s disease, or a psychiatric illness. As a result, it is often misdiagnosed or missed altogether. As additional symptoms appear, it is often easier to make an accurate diagnosis.

The good news is that doctors are increasingly able to diagnose LBD earlier and more accurately as researchers identify which symptoms help distinguish it from similar disorders.

No single test, such as a blood test, can be used to diagnose a frontotemporal disorder. A definitive diagnosis can be confirmed only by a genetic test in familial cases or a brain autopsy after a person dies. To diagnose a probable frontotemporal disorder in a living person, a doctor— usually a neurologist, psychiatrist, or psychologist—will:

Difficult as it is, getting an accurate diagnosis of LBD early on is important so that a person:

• gets the right medical care and avoids potentially harmful treatment
• has time to plan medical care and arrange legal and financial affairs
• can build a support team to stay independent and maximize quality of life

While a diagnosis of LBD can be distressing, some people are relieved to know the reason for their troubling symptoms. It is important to allow time to adjust to the news. Talking about a diagnosis can help shift the focus toward developing a care plan.

Who Can Diagnose LBD?

Many physicians and other medical professionals are not familiar with LBD, so patients may consult several doctors before receiving a diagnosis. Visiting a family doctor is often the first step for people who are experiencing changes in thinking, movement, or behavior. However, neurologists— doctors who specialize in disorders of the brain and nervous system—generally have the expertise needed to diagnose LBD. Geriatric psychiatrists, neuropsychologists, and geriatricians may also be skilled in diagnosing the condition.

If a specialist cannot be found in your community, ask the neurology department of the nearest medical school for a referral. A hospital affiliated with a medical What’s going on? Janet, a 60-year-old executive secretary, began having trouble managing the accounting, paperwork, and other responsibilities of her job. She became increasingly irritable, and her daughter insisted she see a doctor. Janet was diagnosed with depression and stressrelated problems. She was prescribed an antidepressant, but her thinking and concentration problems worsened. When she could no longer function at work, her doctor diagnosed Alzheimer’s disease. A few months later, Janet developed a tremor in her right hand. She was referred to a neurologist, who finally diagnosed Lewy body dementia. 15 school may also have a dementia or movement disorders clinic that provides expert evaluation. See the “Resources” section at the end of this booklet.

Tests Used to Diagnose LBD

Doctors perform physical and neurological examinations and various tests to distinguish LBD from other illnesses. An evaluation may include:

• Medical history and examination—A review of previous and current illnesses, medications, and current symptoms and tests of movement and memory give the doctor valuable information.
• Medical tests—Laboratory studies can help rule out other diseases and hormonal or vitamin deficiencies that can be associated with cognitive changes.
• Brain imaging—Computed tomography or magnetic resonance imaging can detect brain shrinkage or structural abnormalities and help rule out other possible causes of dementia or movement symptoms.
• Neuropsychological tests—These tests are used to assess memory and other cognitive functions and can help identify affected brain regions.

There are no brain scans or medical tests that can definitively diagnose LBD. Currently, LBD can be diagnosed with certainty only by a brain autopsy after death.

However, researchers are studying ways to diagnose LBD more accurately in the living brain. Certain types of neuroimaging—positron emission tomography and single-photon emission computed tomography—have shown promise in detecting differences between dementia with Lewy bodies and Alzheimer’s disease. These methods may help diagnose certain features of the disorder, such as dopamine deficiencies. Researchers are also investigating the use of lumbar puncture (spinal tap) to measure proteins in cerebrospinal fluid that might distinguish dementia with Lewy bodies from Alzheimer’s disease and other brain disorders.

Other Helpful Information

It is important for the patient and a close family member or friend to tell the doctor about any symptoms involving thinking, movement, sleep, behavior, or mood. Also, discuss other health problems and provide a list of all current medications, including prescriptions, over-the-counter drugs, vitamins, and supplements. Certain medications can worsen LBD symptoms.

Caregivers may be reluctant to talk about a person’s symptoms when that person is present. Ask to speak with the doctor privately if necessary. The more information a doctor has, the more accurate a diagnosis can be.

While LBD currently cannot be prevented or cured, some symptoms may respond to treatment for a period of time. A comprehensive treatment plan may involve medications, physical and other types of therapy, and counseling. Changes to make the home safer, equipment to make everyday tasks easier, and social support are also very important.

A skilled care team often can provide suggestions to help improve quality of life for both people with LBD and their caregivers.

Building a Care Team

After receiving a diagnosis, a person with LBD may benefit from seeing a neurologist who specializes in dementia and/or movement disorders. A good place to find an LBD specialist is at a dementia or movement disorders clinic in an academic medical center in your community. If such a specialist cannot be found, a general neurologist should be part of the care team. Ask a primary care physician for a referral.

A doctor can work with other types of healthcare providers. Depending on an individual’s particular symptoms, other professionals may be helpful:

• Physical therapists can help with movement problems through cardiovascular, strengthening, and flexibility exercises, as well as gait
  training and general physical fitness programs.
• Speech therapists may help with low voice volume, voice projection, and swallowing difficulties.
• Occupational therapists help identify ways to more easily carry out everyday activities, such as eating and bathing, to promote independence.
• Music or expressive arts therapists may provide meaningful activities that can reduce anxiety and improve well-being.
• Mental health counselors can help people with LBD and their families learn how to manage difficult emotions and behaviors and
  plan for the future.

Support groups are another valuable resource for both people with LBD and caregivers. Sharing experiences and tips with others in the same situation can help people identify practical solutions to day-to-day challenges and get emotional and social support. To find a support group near you, see the “Resources” section.

Medications

Several drugs and other treatments are available to treat LBD symptoms. It is important to work with a knowledgeable health professional because certain medications can make some symptoms worse. Some symptoms can improve with nondrug treatments.

Cognitive Symptoms

Some medications used to treat Alzheimer’s disease also may be used to treat the cognitive symptoms of LBD. These drugs, called cholinesterase inhibitors, act on a chemical in the brain that is important for memory and thinking. They may also improve behavioral symptoms. (See “Behavioral and Mood Problems” on page 22 for more information.) The U.S. Food and Drug Administration (FDA) approves specific drugs for certain uses after rigorous testing and review. The FDA has approved one Alzheimer’s drug, rivastigmine (Exelon®), to treat cognitive symptoms in Parkinson’s disease dementia. This and other Alzheimer’s drugs can have side effects such as nausea and diarrhea.

Movement Symptoms

LBD-related movement symptoms may be treated with a Parkinson’s medication called carbidopa-levodopa (Sinemet®, Parcopa®, Stalevo®). This drug can help improve functioning by making it easier to walk, get out of bed, and move around. However, it cannot stop or reverse the progress of the disease.

Side effects of this medication can include hallucinations and other psychiatric or behavioral problems. Because of this risk, physicians may recommend not treating mild movement symptoms with medication. If prescribed, carbidopa-levodopa usually begins at a low dose and is increased gradually. Other Parkinson’s medications are less commonly used in people with LBD due to a higher frequency of side effects.

A surgical procedure called deep brain stimulation, which can be very effective in treating the movement symptoms of Parkinson’s disease, is not recommended for people with LBD because it can result in greater cognitive impairment.

People with LBD may benefit from physical therapy and exercise. Talk with your doctor about what physical activities are best.

Sleep Disorders

Sleep problems may increase confusion and behavioral problems in people with LBD and add to a caregiver’s burden. A physician can order a sleep study to identify any underlying sleep disorders such as sleep apnea, restless leg syndrome, and REM sleep behavior disorder.

REM sleep behavior disorder, a common LBD symptom, involves acting out one’s dreams, leading to lost sleep and even injuries to sleep partners. Clonazepam (Klonopin®), a drug used to control seizures and relieve panic attacks, is often effective for the disorder at very low dosages. However, it can have side effects such as dizziness, unsteadiness, and problems with thinking. Melatonin, a naturally occurring hormone used to treat insomnia, may also offer some benefit when taken alone or with clonazepam.

Excessive daytime sleepiness is also common in LBD. If it is severe, a sleep specialist may prescribe a stimulant to help the person stay awake during the day.

Some people with LBD may have difficulty falling asleep. If trouble sleeping at night (insomnia) persists, a physician may recommend a prescription medication to promote sleep. It is important to note that treating insomnia and other sleep problems in people with LBD has not been extensively studied, and that treatments may worsen daytime sleepiness and should be used with caution.

Certain sleep problems can be addressed without medications. Increasing daytime exercise or activities and avoiding lengthy or frequent naps can promote better sleep. Avoiding alcohol, caffeine, or chocolate late in the day can help, too. Some over-the-counter medications can also affect sleep, so review all medications and supplements with a physician.

Behavioral and Mood Problems

Behavioral and mood problems in people with LBD can arise from hallucinations or delusions. They may also be a result of pain, illness, stress or anxiety, and the inability to express frustration, fear, or feeling overwhelmed. The person may resist care or lash out verbally or physically. Caregivers must try to be patient and use a variety of strategies to handle such challenging behaviors. Some behavioral problems can be managed by making changes in the person’s environment and/or treating medical conditions. Other problems may require medication.

The first step is to visit a doctor to see if a medical condition unrelated to LBD is causing the problem. Injuries, fever, urinary tract or pulmonary infections, pressure ulcers (bed sores), and constipation can worsen behavioral problems. Increased confusion can also occur.

Certain medications used to treat LBD symptoms or other diseases may also cause behavioral problems. For example, some sleep aids, pain medications, bladder control medications, and drugs used to treat LBD-related movement symptoms can cause confusion, agitation, hallucinations, and delusions. Similarly, some anti-anxiety medicines can actually increase anxiety in people with LBD. Review your medications with your doctor to determine if any changes are needed.

Not all behavioral problems are caused by illness or medication. A person’s surroundings—including levels of stimulation or stress, lighting, daily routines, and relationships—can lead to behavior issues. Caregivers can alter the home environment to try to minimize anxiety and stress for the person with LBD. In general, people with LBD benefit from having simple tasks, consistent schedules, regular exercise, and adequate sleep. Large crowds or overly stimulating environments can increase confusion and anxiety.

Hallucinations and delusions are among the biggest challenges for LBD caregivers. The person with LBD may not understand or accept that the hallucinations are not real and become agitated or anxious. Caregivers can help by responding to the fears expressed instead of arguing or responding factually to comments that may not be true. By tuning in to the person’s emotions, caregivers can offer empathy and concern, maintain the person’s dignity, and limit further tension.

Cholinesterase inhibitors may reduce hallucinations and other psychiatric symptoms of LBD. These medications may have side effects, such as nausea, and are not always effective. However, they can be a good first choice to treat behavioral symptoms. Cholinesterase inhibitors do not affect behavior immediately, so they should be considered part of a long-term strategy.

Antidepressants can be used to treat depression and anxiety, which are common in LBD. Two types of antidepressants, called selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors, are often well tolerated by people with LBD.

In some cases, antipsychotic medications are necessary to treat LBD-related behavioral symptoms to improve both the quality of life and safety of the person with LBD and his or her caregiver. These types of medications must be used with caution because they can cause severe side effects and can worsen movement symptoms.

If antipsychotics are prescribed, it is very important to use the newer kind, called atypical antipsychotics. These medications should be used at the lowest dose possible and for the shortest time possible to control symptoms. Many LBD experts prefer quetiapine (Seroquel®) or clozapine (Clozaril®, FazaClo®) to control difficult behavioral symptoms. Typical (or traditional) antipsychotics, such as haloperidol (Haldol®), generally should not be prescribed for people with LBD. They can cause dangerous side effects.

Other Treatment Considerations

LBD affects the part of the nervous system that regulates automatic actions like blood pressure and digestion. One common symptom is orthostatic hypotension, low blood pressure that can cause dizziness and fainting. Simple measures such as leg elevation, elastic stockings, and, when recommended by a doctor, increasing salt and fluid intake can help.

If these measures are not enough, a doctor may prescribe medication. Urinary incontinence (loss of bladder control) should be treated cautiously because certain medications used to treat this condition may worsen cognition or increase confusion. Consider seeing a urologist. Constipation can often be treated by exercise and changes in diet, though laxatives and stool softeners may be necessary.

People with LBD are often sensitive to prescription and over-the-counter medications for other medical conditions. Talk with your doctor about any side effects seen in a person with LBD.

If surgery is planned and the person with LBD is told to stop taking all medications beforehand, ask the doctor to consult the person’s neurologist in developing a plan for careful withdrawal. In addition, be sure to talk with the anesthesiologist in advance to discuss medication sensitivities and risks unique to LBD. People with LBD who receive certain anesthetics may become confused or delirious and have a sudden, significant decline in functional abilities, which may become permanent.

Depending on the procedure, possible alternatives to general anesthesia may include a spinal or regional block. These methods are less likely to result in confusion after surgery. Caregivers should also discuss the use of strong pain relievers after surgery, since people with LBD can become delirious if these drugs are used too freely.

Coping with a diagnosis of LBD and all that follows can be challenging. Getting support from family, friends, and professionals is critical to ensuring the best possible quality of life. Creating a safe environment and preparing for the future are important, too. Take time to focus on your strengths, enjoy each day, and make the most of your time with family and friends. Here are some ways to live with LBD day to day.

Getting Help

Your family and close friends are likely aware of changes in your thinking, movement, or behavior. You may want to tell others about your diagnosis so they can better understand the reason for these changes and learn more about LBD. For example, you could say that you have been diagnosed with a brain disorder called Lewy body dementia, which can affect thinking, movement, and behavior. You can say that you will need more help over time. By sharing your diagnosis with those closest to you, you can build a support team to help you manage LBD.

As LBD progresses, you will likely have more trouble managing everyday tasks such as taking medication, paying bills, and driving. You will gradually need more assistance from family members, friends, and perhaps professional caregivers. Although you may be reluctant to get help, try to let others partner with you so you can manage responsibilities together. Remember, LBD affects your loved ones, too. You can help reduce their stress when you accept their assistance.

Finding someone you can talk with about your diagnosis—a trusted friend or family member, a mental health professional, or a spiritual advisor—may be helpful. See the “Resources” section to find supportive services in your area.

Consider Safety

The changes in thinking and movement that occur with LBD require attention to safety issues. Consider these steps:

• Fill out and carry the LBD Medical Alert Wallet Card and present it any time you are hospitalized, require emergency medical care, or meet with your doctors. It contains important information about medication sensitivities.
• Consider subscribing to a medical alert service, in which you push a button on a bracelet or necklace to access 911 if you need emergency help.
• Address safety issues in your home, including areas of fall risk, poor lighting, stairs, or cluttered walkways. Think about home modifications that may be needed, such as installing grab bars in the bathroom or modifying stairs with ramps. Ask your doctor to refer you to a home health agency for a home safety evaluation.
• Talk with your doctor about LBD and driving, and have your driving skills evaluated, if needed.

Plan for Your Future

There are many ways to plan ahead. Here are some things to consider:

• If you are working, consult with a legal and financial expert about planning for disability leave or retirement. Symptoms of LBD will
  interfere with work performance over time, and it is essential to plan now to obtain benefits you are entitled to.
• Consult with an attorney who specializes in elder law or estate planning to help you write or update important documents, such as a
  living will, healthcare power of attorney, and will.
• Identify local resources for home care, meals, and other services before you need them so you know whom to call when the time comes.
• Explore moving to a retirement or continuing care community where activities and varying levels of care can be provided over time, as needed. Ask about staff members’ experience caring for people with LBD.

Find Enjoyment Every Day

It is important to focus on living with LBD. Your attitude can help you find enjoyment in daily life. Despite the many challenges and adjustments, you can have moments of humor, tenderness, and gratitude with the people closest to you.

Make a list of events and activities you can still enjoy—then find a way to do them! For example, listening to music, exercising, or going out for a meal allows you to enjoy time with family and friends. If you can’t find pleasure in daily life, consult your doctor or another healthcare professional to discuss effective ways to cope and move forward. Let your family know if you are struggling emotionally so they can offer support.

As someone who is caring for a person with LBD, you will take on many different responsibilities over time. You do not have to face these responsibilities alone. Many sources of help are available, from adult day centers and respite care to online and in-person support groups.

Below are some important actions you can take to adjust to your new roles, be realistic about your situation, and care for yourself. See the “Resources” section for more information.

Educate Others About LBD

Most people, including many healthcare professionals, are not familiar with LBD. In particular, emergency room physicians and other hospital workers may not know that people with LBD are extremely sensitive to antipsychotic medications. Caregivers can educate healthcare professionals and others by:

• Informing hospital staff of the LBD diagnosis and medication sensitivities, and requesting that the person’s neurologist be consulted
  before giving any drugs to control behavior problems.
• Sharing educational pamphlets and other materials with doctors, nurses, and other healthcare professionals who care for the person with LBD.
• Teaching family and friends about LBD so they can better understand your situation.

Adjust Expectations

You will likely experience a wide range of emotions as you care for the person with LBD. Sometimes, caregiving will feel loving and rewarding. Other times, it will lead to anger, impatience, resentment, or fatigue. You must recognize your strengths and limitations, especially in light of your past relationship with the person. Roles may change between a husband and wife or between a parent and adult children. Adjusting expectations can allow you to approach your new roles realistically and to seek help as needed.

People approach challenges at varied paces. Some people want to learn everything possible and be prepared for every scenario, while others manage best by taking one day at a time. Caring for someone with LBD requires a balance. On one hand, you should plan for the future. On the other hand, you may want to make each day count in personal ways and focus on creating enjoyable and meaningful moments.

Care for Yourself

As a caregiver, you play an essential role in the life of the person with LBD, so it is critical for you to maintain your own health and well-being. You may be at increased risk for poor sleep, depression, or illness as a result of your responsibilities. Watch for signs of physical or emotional fatigue such as irritability, withdrawal from friends and family, and changes in appetite or weight.

All caregivers need time away from caregiving responsibilities to maintain their well-being. Learn to accept help when it’s offered and learn to ask family and friends for help. One option is professional respite care, which can be obtained through home care agencies and adult day programs. Similarly, friends or family can come to the home or take the person with LBD on an outing to give you a break.

Address Family Concerns

Not all family members may understand or accept LBD at the same time, and this can create conflict. Some adult children may deny that parents have a problem, while others may be supportive. It can take a while to learn new roles and responsibilities.

Family members who visit occasionally may not see the symptoms that primary caregivers see daily and may underestimate or minimize your responsibilities or stress. Professional counselors can help with family meetings or provide guidance on how families can work together to manage LBD.

Helping Children and Teens Cope with LBD

When someone has Lewy body dementia, it affects the whole family, including children and grandchildren. Children notice when something “doesn’t seem right.” Telling them in age-appropriate language that someone they know or love has been diagnosed with a brain disorder can help them make sense of the changes they see. Give them enough information to answer questions or provide explanations without overwhelming them.

The organizations listed in the Resources section can help with information about caregiver services and support.

Children and teens may feel a loss of connection with the person with LBD who has problems with attention or alertness. They may also resent the loss of a parent caregiver’s attention and may need special time with him or her. Look for signs of stress in children, such as poor grades at school, withdrawal from friendships, or unhealthy behaviors at home. Parents may want to notify teachers or counselors of the LBD diagnosis in the family so they can watch for changes in the young person that warrant attention.

Here are some other ways parents can help children and teens adjust to a family member with LBD:

• Help them keep up with normal activities such as sports, clubs, and other hobbies outside the home. Suggest ways for kids to engage with the relative with LBD through structured activities or play. For example, the child or teen can make a cup of tea for the person with LBD.
• Find online resources for older children and teens so they can learn about dementia and LBD. See the “Resources” section for more information.

It is important for families to make time for fun. Many challenges can be faced when they are balanced with enjoyable times. While LBD creates significant changes in family routines, children and teens will cope more effectively if the disorder becomes part of, but not all of, their lives.