Lewy Body Dementias

Lewy body dementias include dementia with Lewy bodies (DLB) and Parkinson’s disease with dementia (PDD) and are the second most frequent cause of dementia in elderly adults. These degenerative brain diseases are associated with abnormal clumps of a protein called alpha-synuclein. These clumps, called Lewy bodies, are found in nerve cells throughout the outer layer of the brain (the cerebral cortex) and deep inside the midbrain and brainstem. Patients with these diseases experience progressive cognitive decline, although there is considerable variability in symptoms between patients. Common symptoms include problems with movement, visual hallucinations, and fluctuations in thinking skills or attention.

Dementia-With-Lewy-BodiesCauses

The cause of Lewy body dementias is unknown in most cases. Monogentic forms of Lewy body disorders, where a patient inherited the disease from one parent, are rare and comprise about 10% of cases. These familial variants are more common in patients with an earlier age of disease onset. The majority of cases are thought to result from complex interactions among different “susceptibility” genes and environmental risk factors. The primary environmental factors that have been implicated in increasing risk of some cases of Lewy body disorders include pesticide or other chemical exposure and head injury. There are many research studies currently being conducted to better understand the role that genetics and environment play in Lewy body disorders.

The underlying brain changes of Lewy body dementias involve the clumping of a protein in the brain called alpha-synuclein. These clumps are called “Lewy bodies.” The regional distribution of these clumps in the brain influences the types of symptoms (e.g., cognitive, motor, psychiatric). Lewy body dementias are also associated with reductions in important brain chemicals called neurotransmitters, including dopamine and acetylcholine.

Parkinson’s Disease versus Lewy Bodies

Some patients with Parkinson’s disease (PD) experience no or only subtle cognitive decline and their primary limitation is their motor disorder. However, many patients with Parkinson’s disease will develop dementia as a consequence of the disease. When dementia develops after an established motor disorder, we call the disease PDD. In contrast, when the dementia develops prior to or at the same time as the motor disorder, we call the disease DLB. Although the initial sequence of symptoms differs in PDD and DLB, as the disorders progress, the symptoms and the underlying brain changes are much more similar than they are different. As such, many researchers and clinicians think of PDD and DLB as being on a continuum of a similar disease process rather than as two distinct entities.

Signs and Symptoms

The parkinsonian motor syndrome is similar in PDD and DLB and can include slowed movement (bradykinesia), rigidity (muscles feel still and resist movement), tremor and gait difficulties. In terms of the cognitive difficulties, both disorders can involve progressive problems involving visual spatial processing, attention, executive dysfunction (e.g., planning and multi-tasking) and memory. Psychiatric symptoms are common and can include anxiety, depression, hallucinations (usually visual) and delusions (false beliefs). Sleep problems including excessive daytime drowsiness and difficulty staying asleep are common. Many patients exhibit REM sleep behavior disorder (RBD) that manifests by the patient acting out his or her dreams. Many patients experience constipation, repeated falls, syncope and loss of smell. Individuals diagnosed with Lewy body dementias often have adverse reactions including confusion when taking medications that affect the brain, such as anti-anxiety drugs (examples: Valium®, Ativan®), anticholinergic drugs (examples: Benadryl®, Detrol®), and antiparkinson’s drugs (examples: Sinemet®, Mirapex®). To avoid adverse reactions to medications, physicians should carefully monitor medications, introduce medications one at a time and prescribe minimal doses when possible.

Diagnosis

An extensive neurological and neuropsychological evaluation is essential for Lewy body dementia diagnosis. Structural brain imaging (e.g., MRI or CT) and laboratory tests are used to rule out other diagnoses. Lewy body dementias can be difficult to diagnose because they can resemble and overlap with other causes of dementia like Alzheimer’s disease, other parkinsonian syndromes (examples: progressive supranuclear palsy, multiple system atrophy, corticobasal syndrome), and vascular dementia. As in many neurodegenerative diseases, a definitive diagnosis in only available after an autopsy. However, clinical diagnosis by experienced providers can be quite accurate and reliable.

Disease Progression

Onset of the disorder usually occurs in older adults, and disease risk increases with age. There is substantial variability in the course of the illness. In general, symptoms progress over several years as cognitive decline becomes more prominent and psychiatric symptoms emerge or worsen. The progression of symptoms represents increasing pathology in the brain including more widespread Lewy bodies, loss of neurotransmitters (examples: dopamine and acetylcholine) and nerve cell death.

Management and Treatment

Lewy body dementia patients are often frail, and their symptoms can worsen quickly when faced with infection, medication reactions or changes in the environment; these risks should be closely monitored. Nonpharmacologic interventions, including physical, occupational and speech therapy, community resources and assistance with home care should always be considered. The motor symptoms of Lewy body dementias are generally treated with dopaminergic therapies. These medications are usually helpful in decreasing the severity of motor symptoms. However, it is advisable for these medications to be initially prescribed at a low dosage and gradually titrated upwards as necessary given the possibility of potential side effects such as worsening confusion and hallucinations. Cognitive symptoms of Lewy body dementias are often treated with cholinesterase inhibitors (e.g., Rivastigmine®, Aricept®). These medications can improve the attention deficits, cognitive fluctuations, neuropsychiatric symptoms (e.g., hallucinations, apathy, anxiety), and sleep disturbances by boosting acetylcholine in the brain, a neurotransmitter that is severely reduced by these diseases. Memantine has also been tried for treatment of cognitive impairment in Lewy body dementias. In general, the results have suggested that this drug is well-tolerated but not reliably effective. Depression is very common in Lewy body dementias and can be treated with antidepressant medications.

For psychotic symptoms (e.g., hallucinations or delusions) that are troublesome to the patient and/or family and that are non-responsive to psychosocial interventions (e.g., making changes in the patient’s environment) or cholinesterase inhibitor treatment, atypical second generation antipsychotic medications such as risperidone (Risperdol®) and quetiapine (Seroquel®) can be tried but must be used cautiously due to the risk of motor and cognitive side effects. Older, first generation antipsychotic drugs such as haloperidol (Haldol®) or chlorpromazine (Thorazine®) should be avoided because they can cause extreme adverse reactions in many Lewy body dementia patients. A patient treated with these drugs could become catatonic, lose cognitive function and/or develop more muscle rigidity.

The symptomatic treatments available and described above do not slow down the disease course. The current search for disease-modifying drugs is focused primarily on preventing the misfolding and buildup of alpha-synuclein pathology in the brain.

Resources for Lewy Body Dementias

More Information

The following publication was prepared by the Office of Communications and Public Liaison, National Institute of Neurological Disorders and Stroke, National Institutes of Health at Bethesda, Maryland. It is available as a free download.
Lewy Body Dementia: Information for Patients, Families, and ProfessionalsLewy Body Dementia: Information for Patients, Families, and Professionals

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