Dementia With Lewy Bodies

Updated: Sep 27, 2017
  • Author: Howard A Crystal, MD; Chief Editor: Jasvinder Chawla, MD, MBA  more...
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Overview

Practice Essentials

Dementia with Lewy bodies (DLB) is a progressive, degenerative dementia of unknown etiology. Affected patients generally present with dementia preceding motor signs, particularly with visual hallucinations and episodes of reduced responsiveness.

Signs and symptoms

Symptoms and signs of DLB may result, in part, from disruption of bidirectional information flow from the striatum to the neocortex, especially the frontal lobe.

The following clinical features help to distinguish DLB from Alzheimer disease:

  • Fluctuations in cognitive function with varying levels of alertness and attention (eg, excessive daytime drowsiness despite adequate nighttime sleep or daytime sleep >2 hours, staring into space for long periods, episodes of disorganized speech)
  • Visual hallucinations
  • Parkinsonian motor features
  • Relatively early extrapyramidal features (vs may occur late in Alzheimer disease)
  • Anterograde memory loss: May be less prominent (vs prominent early sign in Alzheimer disease)
  • More prominent executive function deficits and visuospatial impairment (eg, Stroop, digit span backwards)

Other symptoms that may alert clinicians to the diagnosis of DLB (vs Alzheimer disease) include the following:

  • Nonvisual hallucinations
  • Delusions
  • Unexplained syncope
  • Rapid eye movement sleep disorder
  • Neuroleptic sensitivity

See Clinical Presentation for more detail.

Diagnosis

Examination of cognition and mental status in patients with suspected DLB may include the following findings:

  • Impaired, but relatively conserved cognition
  • Fluctuating cognition: Periods of being alert, coherent, and oriented alternating with periods during which the patient is confused and unresponsive to questions
  • Retrieval from memory: May be relatively worse than memory storage
  • May do relatively well with confrontation naming tests but poorly on tests of visuospatial skills (eg, drawing a clock, copying figures)

Other findings on physical examination may include the following:

  • Some parkinsonian signs but usually not enough to meet the criteria for a diagnosis of Parkinson disease
  • Mild gait impairment: Relatively frequent; should not be ascribed to old age or osteoarthritis.
  • Resting tremor: Occurs less frequently than in Parkinson disease
  • May exhibit myoclonus before severe dementia
  • Orthostatic hypotension: Particularly common in DLB [1]

Testing

No sensitive or specific blood or urine tests are currently available for DLB. Laboratory studies should include those usually ordered in a dementia evaluation, including the following:

  • Chemistry panel
  • Complete blood count
  • Thyroid studies
  • Vitamin B-12 levels
  • Syphilis, Lyme disease, or human immunodeficiency virus testing, when appropriate

Cerebrospinal fluid examination is not required in routine cases. In certain circumstances, neuropsychologic testing is helpful in differentiating DLB from Alzheimer disease and in establishing a baseline for future comparison.

Patients with DLB may have changes on electroencephalography earlier than do patients with Alzheimer disease, but whether this difference is diagnostically useful is not clear.

Imaging studies

The following radiologic studies of the brain may be used to evaluate patients with suspected DLB:

  • Magnetic resonance imaging: To distinguish DLB from vascular dementia
  • Computed tomography scanning
  • Single photon emission computed tomography
  • Positron emission tomography scanning

See Workup for more detail.

Management

Patients who have DLB with mild hallucinations and agitation may not require medical treatment. When medication is used, acetylcholinesterase inhibitors should be tried first. When cholinesterase inhibitors are ineffective, most experts recommend atypical neuroleptics such as clozapine, quetiapine, or aripiprazole. Avoid standard neuroleptics, such as haloperidol, because of neuroleptic sensitivity.

Pharmacotherapy

As yet, no compelling data indicate that medications can decrease the rate of cognitive decline. Medications can be used to treat agitation and hallucinations, as well as depression, and to improve cognition and/or alertness.

The following medications are used in patients who have DLB:

  • Cholinesterase inhibitors (eg, donepezil, rivastigmine, rivastigmine patch, galantamine)
  • 2nd-generation antipsychotics (eg, clozapine, quetiapine, aripiprazole)
  • Antidepressants (eg, venlafaxine, paroxetine, sertraline, fluoxetine)
  • Benzodiazepines (eg, clonazepam)
  • Dopamine precursors (eg, levodopa and carbidopa)

See Treatment and Medication for more detail.

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Background

Dementia with Lewy bodies (DLB) is a progressive, degenerative dementia. Frederick Lewy first described Lewy bodies (LBs)—cytoplasmic inclusions found in cells of the substantia nigra in patients with idiopathic Parkinson disease —in 1914. (See Etiology.)

In the 1960s, several pathologists described patients with dementia who had LBs of the neocortex. However, such cases were presumed to be rare until the mid-1980s, when sensitive immunocytochemical methods to identify LBs were developed. DLB was then recognized as being far more common than previously thought. (See Workup.)

The relationship of DLB and Parkinson disease is an area of considerable controversy, particularly because dementia frequently occurs in Parkinson disease. Many investigators believe that a spectrum of LB disorders exists.

Clinical criteria for DLB were first proposed in 1996 [2] and modified in the subsequent DLB Consortium reports. [3] Several clinicopathologic studies have assessed the sensitivity and specificity of these clinical criteria. (See Presentation and Workup.) [4, 5]

The third report of the DLB Consortium, headed by Ian McKeith, discussed an arbitrary 1-year rule to distinguish DLB from Parkinson disease with dementia. [6] According to the report, if parkinsonism has been present for 12 months or longer before cognitive impairment is detected, the disorder is called Parkinson disease with dementia; otherwise, it is called DLB. The report recognized that this rule may be difficult to apply in clinical practice. When dementia precedes motor signs, particularly with visual hallucinations and episodes of reduced responsiveness, the diagnosis of DLB should be considered. (See Presentation.)

Location and composition of Lewy bodies

Postmortem examinations in patients with Parkinson disease and those with DLB have demonstrated LBs in the substantia nigra and possibly in the locus ceruleus, dorsal raphe, substantia innominata, and dorsal motor nucleus of cranial nerve X (CNX, the vagus nerve). LBs are found in the neocortex of many patients with idiopathic Parkinson disease and in all patients with DLB. DLB overlaps parkinsonian dementias. (See Workup.)

The primary constituent of LBs is alpha synuclein, a presynaptic protein, the function of which is unknown. Neurofilament proteins and ubiquitin are other important constituents of LBs. Numerous neurotransmitters, including acetylcholine (ACh), are diminished in DLB. The decrease in ACh may be more severe than in Alzheimer disease. (See Treatment and Medication.)

DLB and Alzheimer disease

Up to 40% of patients with Alzheimer disease have concomitant LBs. These mixed cases are sometimes called the LB variant of Alzheimer disease (LBV-AD) and represent an overlap syndrome between DLB and Alzheimer disease. Signs and symptoms of LBV-AD also overlap between DLB and Alzheimer disease. [7]

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Etiology

The etiology of DLB is not known. Symptoms and signs of DLB probably result, in part, from disruption of bidirectional information flow from the striatum to the neocortex, especially the frontal lobe. The cause is multifactorial. Altered levels of neuromodulators and/or neurotransmitters (eg, ACh, dopamine) influence the function of many neuronal circuits. In DLB, nonpyramidal cells in layers V and VI of the neocortex may contain LBs. Their function in neocortical information processing and in relaying data to subcortical regions probably is impaired. The etiology of fluctuations in cognitive function, which characterize DLB, is unknown. [8]

Nagahama et al found that different types of psychotic symptoms in patients with DLB correlated with perfusion changes in different parts of the brain. Single-photon emission computed tomography (SPECT) scanning studies in 145 DLB patients revealed the following [9] :

  • Visual hallucinations - Were related to hypoperfusion of the parietal and occipital association cortices
  • Misidentifications - Were related to hypoperfusion of the limbic-paralimbic structures
  • Delusions - Were related to hyperperfusion of the frontal cortices

Genetics

Rare cases of familial DLB have been reported. Overrepresentation of apolipoprotein E subtype 4 (ApoE4) genotype has been found in patients with DLB, but only in those whose disease has occurred concomitantly with Alzheimer disease.

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Epidemiology

Occurrence in the United States

Findings from autopsy studies suggest that DLB accounts for 10-20% of dementias. However, because the sensitivity and specificity of clinical diagnosis are poor, no good epidemiologic data on the incidence or prevalence of DLB are available.

International occurrence

Autopsy studies in Europe and Japan indicate that the frequency of DLB is comparable with that reported in studies from the United States. A prospective, population-based study in a cohort of persons over the age of 65 years in southwestern France found an incidence of 112 cases per 100,000 person-years for suspected DLB. [10]

Race-, sex-, and age-related demographics

DLB has been described in Asian, African, and European races. Data concerning the relative frequency of DLB in different races are not available. Most studies suggest that DLB is slightly more common in men than in women.

DLB is a disease of late middle age and old age. The aforementioned study in southwestern France found that the incidence of DLB increased continuously with advancing age, whereas that of Parkinson disease decreased after age 85 years. [10]

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Prognosis

DLB is a disorder of inexorable progression. The rate of progression varies, and some investigators think that progression is faster than that of Alzheimer disease. Patients eventually die from complications of immobility, poor nutrition, and swallowing difficulties.

Morbidity and mortality

The following morbidities are associated with DLB:

  • With severe disease, patients may experience swallowing problems that can lead to impaired nutrition
  • Patients are at risk for falls because of impaired mobility and balance
  • Because of prolonged bed rest, patients are at risk for decubitus ulcers
  • Dysphagia and immobility also can lead to pneumonia
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Patient Education

Primary caregivers need information about the course of the disease and the management of symptoms such as agitation, hallucinations, and cognitive fluctuations. Family members and physicians may mistake fluctuations for transient ischemic attacks.

Family members should be made aware that DLB eventually affects job performance. Depending on the patient's occupation and level of dysfunction, medical leave of absence or early retirement may be advised. Driving privileges need to be addressed by the patient, family, caregivers, primary care physician, and neurologist. Information concerning issues such as daycare and home health aides can also be useful.

Children of patients with DLB may request information concerning genetic risks or neuroprotective treatment regimens.

For patient education information, see the Brain and Nervous System Center, as well as Dementia Overview, Dementia With Lewy Bodies, and Dementia Medication Overview.

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