Lewy Body Dementia and Parkinson Disease Dementia
Lewy body dementia is chronic cognitive deterioration characterized by cellular inclusions called Lewy bodies in the cytoplasm of cortical neurons. Parkinson disease dementia is cognitive deterioration characterized by Lewy bodies in the substantia nigra; it develops late in Parkinson disease.
Dementia is chronic, global, usually irreversible deterioration of cognition. Lewy body dementia is the 3rd most common dementia. Age of onset is typically > 60.
Lewy bodies are spherical, eosinophilic, neuronal cytoplasmic inclusions composed of aggregates of α-synuclein, a synaptic protein. They occur in the cortex of some patients with primary Lewy body dementia. Neurotransmitter levels and neuronal pathways between the striatum and the neocortex are abnormal.
Lewy bodies also occur in the substantia nigra of patients with Parkinson disease, and dementia (Parkinson disease dementia) may develop late in the disease. About 40% of patients with Parkinson disease develop Parkinson disease dementia, usually after age 70 and about 10 to 15 yr after Parkinson disease has been diagnosed.
Because Lewy bodies occur in Lewy body dementia and in Parkinson disease dementia, some experts think that the 2 disorders may be part of a more generalized synucleinopathy affecting the central and peripheral nervous systems. Lewy bodies sometimes occur in patients with Alzheimer disease, and patients with Lewy body dementia may have neuritic plaques and neurofibrillary tangles. Lewy body dementia, Parkinson disease, and Alzheimer disease overlap considerably. Further research is needed to clarify the relationships among them.
Both Lewy body dementia and Parkinson disease dementia have a progressive course with a poor prognosis.
Dementia should not be confused with delirium although cognition is disordered in both. The following usually helps distinguish dementia from delirium:
Other specific characteristics also help distinguish the dementia and delirium (see Table: Differences Between Delirium and Dementia*).
Initial cognitive deterioration in Lewy body dementia resembles that of other dementias (see Dementia : Symptoms and Signs); it involves deterioration in memory, attention, and executive function and behavioral problems.
Extrapyramidal symptoms (typically including rigidity, bradykinesia, and gait instability) occur (see also Overview of Movement and Cerebellar Disorders). However, in Lewy body dementia (unlike in Parkinson disease), cognitive and extrapyramidal symptoms usually begin within 1 yr of each other. Also, the extrapyramidal symptoms differ from those of Parkinson disease: In Lewy body dementia, tremor does not occur early, rigidity of axial muscles with gait instability occurs early, and deficits tend to be symmetric. Repeated falls are common.
Fluctuating cognitive function is a relatively specific feature of Lewy body dementia. Periods of being alert, coherent, and oriented may alternate with periods of being confused and unresponsive to questions, usually over a period of days to weeks but sometimes during the same interview.
Memory is impaired, but the impairment appears to result more from deficits in alertness and attention than in memory acquisition; thus, short-term recall is affected less than digit span memory (ability to repeat 7 digits forward and 5 backward).
Patients may stare into space for long periods. Excessive daytime drowsiness is common.
Visuospatial and visuoconstructional abilities (tested by block design, clock drawing, or figure copying) are affected more than other cognitive deficits.
Visual hallucinations are common and often threatening, unlike the benign hallucinations of Parkinson disease. Auditory, olfactory, and tactile hallucinations are less common. Delusions occur in 50 to 65% of patients and are often complex and bizarre, compared with the simple persecutory ideation common in Alzheimer disease.
Autonomic dysfunction is common, and unexplained syncope may result. Autonomic dysfunction may occur simultaneously with or occur after onset of cognitive deficits. Extreme sensitivity to antipsychotics is typical.
Many patients have rapid eye movement (REM) sleep behavior disorder, a parasomnia characterized by vivid dreams without the usual physiologic paralysis of skeletal muscles during REM sleep. As a result, dreams may be acted out, sometimes injuring the bed partner.
In Parkinson disease dementia (unlike in Lewy body dementia), cognitive impairment that leads to dementia typically begins 10 to 15 yr after motor symptoms have appeared.
Parkinson disease dementia may affect multiple cognitive domains including attention, memory, and visuospatial, constructional, and executive functions. Executive dysfunction typically occurs earlier and is more common in Parkinson disease dementia than in Alzheimer disease.
Psychiatric symptoms (eg, hallucinations, delusions) appear to be less frequent and/or less severe than in Lewy body dementia.
In Parkinson disease dementia, postural instability and gait abnormalities are more common, motor decline is more rapid, and falls are more frequent than in Parkinson disease without dementia.
Diagnosis is clinical, but sensitivity and specificity are poor.
A general diagnosis of dementia requires all of the following:
Evaluation of cognitive function involves taking a history from the patient and from someone who knows the patient plus doing a bedside mental status examination or, if bedside testing is inconclusive, formal neuropsychologic testing (see Dementia : Assessment of cognitive function).
Diagnosis of Lewy body dementia is considered probable if 2 of the following 3 features are present and is considered possible if only one is present:
Supportive evidence consists of repeated falls, syncope, REM sleep disorder, and sensitivity to antipsychotics.
Overlap of symptoms in Lewy body dementia and Parkinson disease dementia may complicate diagnosis. When motor deficits (eg, tremor, bradykinesia, rigidity) precede and are more severe than cognitive impairment, Parkinson disease dementia is usually diagnosed. When early cognitive impairment (particularly executive dysfunction) and behavioral disturbances predominate, Lewy body dementia is usually diagnosed.
Because patients with Lewy body dementia often have impaired alertness, which is more characteristic of delirium than dementia, evaluation for deliriumshould be done, particularly for common causes such as
CT and MRI show no characteristic changes but are helpful initially in ruling out other causes of dementia. PET with fluorine-18 (18F)–labeled deoxyglucose (fluorodeoxyglucose, or FDG) and single-photon emission CT (SPECT) with 123I-FP-CIT (N-3-fluoropropyl-2β-carbomethoxy-3β-[4-iodophenyl]-tropane), a fluoroalkyl analog of cocaine, may help identify Lewy body dementia but are not routinely done.
Definitive diagnosis requires autopsy samples of brain tissue.
Treatment is generally supportive. For example, the environment and should be bright, cheerful, and familiar, and it should be designed to reinforce orientation (eg, placement of large clocks and calendars in the room). Measures to ensure patient safety (eg, signal monitoring systems for patients who wander) should be implemented.
Troublesome symptoms can be treated.
Cholinesterase inhibitors may improve cognitive function and may be helpful.
Rivastigmine, a cholinesterase inhibitor, can be used to treat Lewy body dementia and Parkinson disease dementia. A starting dose of 1.5 mg po bid may be titrated upward as needed to 6 mg bid to try to improve cognition. Other cholinesterase inhibitors may also be used.
In about half of patients, extrapyramidal symptoms respond to antiparkinsonian drugs, but psychiatric symptoms may worsen. If such drugs are needed, levodopa is preferred.
In Lewy body dementia, traditional antipsychotics, even at very low doses, tend to acutely worsen extrapyramidal symptoms and are best avoided.
Because Lewy bodies occur in Lewy body dementia and in Parkinson disease, some experts hypothesize that the 2 disorders are part of the same synucleinopathy affecting the central and peripheral nervous systems.
Suspect Lewy body dementia if dementia develops nearly simultaneously with parkinsonian features and when dementia is accompanied by fluctuations in cognition, loss of attention, psychiatric symptoms (eg, visual hallucinations; complex, bizarre delusions), and autonomic dysfunction.
Suspect Parkinson disease dementia if dementia begins years after parkinsonian features, particularly if executive dysfunction occurs early.
Consider use of rivastigmine and sometimes other cholinesterase inhibitors to try to improve cognition.