eMedicine Specialties > Neurology > Behavioral Neurology and Dementia

Dementia With Lewy Bodies

Author: Howard A Crystal, MD, Professor, Departments of Neurology and Pathology, State University of New York Downstate; Consulting Staff, Department of Neurology, University Hospital and Kings County Hospital Center
Contributor Information and Disclosures

Updated: Dec 23, 2009

Introduction

Background

Frederick Lewy first described Lewy bodies (LBs) — cytoplasmic inclusions found in cells of the substantia nigra in patients with idiopathic Parkinson's disease — in 1914. 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. Dementia with LBs (DLB) was then recognized as being far more common than previously thought.

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

The third report of the DLB Consortium headed by Ian McKeith discusses an arbitrary 1-year rule to distinguish DLB from Parkinson's disease with dementia.1 If parkinsonism has been present for 12 months or longer before cognitive impairment is detected, the disorder is called Parkinson's disease with dementia; otherwise, it is called DLB. The report recognizes 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. Clinical criteria for DLB were first proposed in 19962 and modified in the subsequent DLB Consortium reports3 . Several clinicopathological studies have assessed the sensitivity and specificity of these clinical criteria.4,5 These clinical features are discussed below.

Postmortem examinations in both Parkinson's disease and DLB patients demonstrate LBs in the substantia nigra and possibly in the locus ceruleus, dorsal raphe, substantia innominata, and dorsal motor nucleus of the vagus. LBs are found in the neocortex of many patients with idiopathic Parkinson's disease and in all patients with DLB. DLB overlaps parkinsonian dementias.

Pathophysiology

  • 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, acetylcholine [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 the fluctuations in cognitive function, which characterize DLB, is unknown.
  • Nagahama et al found that different types of psychotic symptoms in patients with DLB correlate with perfusion changes in different parts of the brain. Single-photon emission CT studies in 145 DLB patients showed that visual hallucinations were related to hypoperfusion of the parietal and occipital association cortices; misidentifications were related to hypoperfusion of the limbic-paralimbic structures; and delusions were related to hyperperfusion of the frontal cortices.6

Frequency

United States

Findings from autopsy studies suggest that DLB accounts for 10-20% of dementias. Up to 40% of patients with Alzheimer's disease have concomitant LBs. These mixed cases are sometimes called the LB variant of Alzheimer's disease (LBV-AD) and represent an overlap syndrome between DLB and Alzheimer's disease. Signs and symptoms of LBV-AD also overlap between DLB and Alzheimer's disease. Because the sensitivity and specificity of clinical diagnosis are poor, no good epidemiologic data on incidence or prevalence of DLB are available.

International

  • 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 per 100,000 person-years for suspected DLB.7

Mortality/Morbidity

  • Dementing illnesses (including DLB) shorten life expectancy.
  • 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.

Race

DLB has been described in Asian, African, and European races. Data concerning the relative frequency of DLB in different races are not available.

Sex

Most studies suggest that DLB is slightly more common in men than in women.

Age

DLB is a disease of late middle age and old age. A prospective population-based study in a cohort of persons over the age of 65 years in southwestern France found that the incidence of DLB increased continuously with advancing age, whereas that of Parkinson's disease decreased after age 85 years.7

Clinical

History

  • DLB is a progressive degenerative dementia.
  • The following clinical features help distinguish DLB from Alzheimer's disease:
    • Fluctuations in cognitive function with varying levels of alertness and attention
      • Clues to the presence of fluctuations include excessive daytime drowsiness (if nighttime sleep is adequate) or daytime sleep longer than 2 hours, staring into space for long periods, and episodes of disorganized speech.
    • Visual hallucinations
    • Parkinsonian motor features
  • Although extrapyramidal features may occur late in the course of Alzheimer's disease, they appear relatively early in DLB.
  • Whereas patients with Alzheimer's disease virtually always have anterograde memory loss as a prominent symptom and sign early in the course of the illness, anterograde memory loss may be less prominent in DLB. McKeith et al have suggested that patients with DLB do relatively better on tests of confrontation naming, short and medium recall, and recognition than Alzheimer's disease patients, whereas Alzheimer's disease patients do better on tests of verbal fluency, visual perception, and performance tasks.8
  • Executive function deficits and visuospatial impairment may be more prominent in persons with DLB than in those with Alzheimer's disease (eg, Stroop, digit span backwards).
  • Other symptoms that may alert clinicians to the diagnosis of DLB (versus Alzheimer's disease) include the following:
    • Nonvisual hallucinations
    • Delusions
    • Unexplained syncope
    • Rapid eye movement sleep disorder
    • Neuroleptic sensitivity

Physical

  • Patients usually have impaired cognition consistent with dementia.
  • Cognitive function, as measured by Mini-Mental State Examination (MMSE) scores, appear to be relatively preserved in DLB, compared with Alzheimer's disease (AD) or AD+DLB (p < 0.01). Nelson et al evaluated data from two large, multicenter data registries (6,340 cases in total) and found that final MMSE scores were 15.6 (+/- 8.7) in persons with DLB, 10.7 (+/- 8.6) in persons with AD, and 10.6 (+/- 8.6) in those with AD+DLB.9
  • An important observation during mental status testing is that the patient has periods of being alert, coherent, and oriented that alternate with periods of being confused and unresponsive to questions (although awake). This fluctuation is a relatively specific feature of DLB.
  • Retrieval from memory may be relatively worse than memory storage.
  • Patients may do relatively well with confrontation naming tests and poorly on tests of visuospatial skills (eg, drawing a clock, copying figures).
  • Patients may have some parkinsonian signs but usually not enough to meet the criteria for a diagnosis of Parkinson's disease.
  • Mild gait impairment is relatively frequent and should not be ascribed to old age or osteoarthritis.
  • Resting tremor occurs less frequently than in Parkinson's disease.
  • Myoclonus may occur before severe dementia.
  • Orthostatic hypotension appears to be particularly common in patients with DLB, even when dementia is mild.10

Causes

  • The etiology of DLB is not known.
  • Rare cases of familial DLB have been reported.
  • Apolipoprotein E subtype 4 (ApoE4) genotype is overrepresented only when DLB occurs with concomitant Alzheimer's disease.

More on Dementia With Lewy Bodies

Overview: Dementia With Lewy Bodies
Differential Diagnoses & Workup: Dementia With Lewy Bodies
Treatment & Medication: Dementia With Lewy Bodies
Follow-up: Dementia With Lewy Bodies
References
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References

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Further Reading

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Keywords

Lewy body dementia, DLB, LB, Lewy body variant of Alzheimer disease, diffuse Lewy body disease, senile dementia of the Lewy body type, idiopathic Parkinson disease, Parkinson's disease, Parkinson disease with dementia, PD with dementia, parkinsonian dementias, Alzheimer disease, Alzheimer's disease, dementia with Lewy bodies, dementia with LBs

progressive degenerative dementia, nonvisual hallucinations, neuroleptic sensitivity, unexplained syncope, delusions, rapid eye movement sleepdisorder, myoclonus, apolipoprotein genotype E subtype 4, apoE4 genotype

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Contributor Information and Disclosures

Author

Howard A Crystal, MD, Professor, Departments of Neurology and Pathology, State University of New York Downstate; Consulting Staff, Department of Neurology, University Hospital and Kings County Hospital Center
Howard A Crystal, MD is a member of the following medical societies: American Academy of Neurology and American Neurological Association
Disclosure: Medivations Honoraria Consulting

Medical Editor

Robert A Hauser, MD, MBA, Professor of Neurology, Molecular Pharmacology and Physiology, Director, Parkinson's Disease and Movement Disorders Center, University of South Florida; Clinical Chair, Signature Interdisciplinary Program in Neuroscience
Robert A Hauser, MD, MBA is a member of the following medical societies: American Academy of Neurology, American Medical Association, American Society of Neuroimaging, and Movement Disorders Society
Disclosure: Allergan Sales, LLC Honoraria Speaking and teaching; Boehringer Ingelheim  Honoraria Consulting; Genzyme Corporation Honoraria Consulting; GlaxoSmithKline Honoraria Consulting; IMPAX Laboratories, Inc. Honoraria Consulting; Novartis Pharmaceuticals Corp. Honoraria Consulting; Schering Plough  Consulting; Solvay Pharmeceuticals Honoraria Consulting; Teva Neuroscience Honoraria Speaking and teaching

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Richard J Caselli, MD, Professor, Department of Neurology, Mayo Medical School, Rochester, MN; Chair, Department of Neurology, Mayo Clinic of Scottsdale
Richard J Caselli, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Medical Association, American Neurological Association, and Sigma Xi
Disclosure: Nothing to disclose.

Chief Editor

Helmi L Lutsep, MD, Professor, Department of Neurology, Oregon Health & Science University; Associate Director, Oregon Stroke Center
Helmi L Lutsep, MD is a member of the following medical societies: American Academy of Neurology and American Stroke Association
Disclosure: Co-Axia Consulting fee Review panel membership; Talecris Consulting fee Review panel membership; AGA Medical Consulting fee Review panel membership; Boehringer Ingelheim Honoraria Speaking and teaching; Concentric Medical Consulting fee Review panel membership; Abbott Consulting fee Consulting; Sanofi  Consulting

 
 
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