eMedicine Specialties > Neurology > Behavioral Neurology and Dementia

Dementia With Lewy Bodies

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 10, 2008

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 neuromodulator and/or neurotransmitter levels (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.

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.

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.

Clinical

History

  • DLB is a progressive degenerative dementia.
  • The following clinical features that 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.6
  • 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.
  • 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.

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.

Contents

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

  1. McKeith IG, Dickson DW, Lowe J, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology. Dec 27 2005;65(12):1863-72. [Medline].

  2. McKeith IG, Galasko D, Kosaka K, et al. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology. Nov 1996;47(5):1113-24. [Medline].

  3. McKeith IG, Perry EK, Perry RH. Report of the second dementia with Lewy body international workshop: diagnosis and treatment. Consortium on Dementia with Lewy Bodies. Neurology. Sep 22 1999;53(5):902-5. [Medline].

  4. McKeith IG, Ballard CG, Perry RH, et al. Prospective validation of consensus criteria for the diagnosis of dementia with Lewy bodies. Neurology. Mar 14 2000;54(5):1050-8. [Medline].

  5. Verghese J, Crystal HA, Dickson DW, Lipton RB. Validity of clinical criteria for the diagnosis of dementia with Lewy bodies. Neurology. Dec 10 1999;53(9):1974-82. [Medline].

  6. McKeith IG, Rowan E, Askew K, et al. More severe functional impairment in dementia with lewy bodies than Alzheimer disease is related to extrapyramidal motor dysfunction. Am J Geriatr Psychiatry. Jul 2006;14(7):582-8. [Medline].

  7. Boeve BF, Silber MH, Ferman TJ. Melatonin for treatment of REM sleep behavior disorder in neurologic disorders: results in 14 patients. Sleep Med. Jul 2003;4(4):281-4. [Medline].

  8. Clark CM, Xie S, Chittams J, et al. Cerebrospinal fluid tau and beta-amyloid: how well do these biomarkers reflect autopsy-confirmed dementia diagnoses?. Arch Neurol. Dec 2003;60(12):1696-702. [Medline].

  9. Collerton D, Burn D, McKeith I, O'Brien J. Systematic review and meta-analysis show that dementia with Lewy bodies is a visual-perceptual and attentional-executive dementia. Dement Geriatr Cogn Disord. 2003;16(4):229-37. [Medline].

  10. Ferman TJ, Smith GE, Boeve BF, et al. DLB fluctuations: specific features that reliably differentiate DLB from AD and normal aging. Neurology. Jan 27 2004;62(2):181-7. [Medline].

  11. Fernandez HH, Wu CK, Ott BR. Pharmacotherapy of dementia with Lewy bodies. Expert Opin Pharmacother. Nov 2003;4(11):2027-37. [Medline].

  12. Galvin JE. Dementia with Lewy bodies. Arch Neurol. Sep 2003;60(9):1332-5. [Medline].

  13. Geldmacher DS. Visuospatial dysfunction in the neurodegenerative diseases. Front Biosci. Sep 1 2003;8:e428-36. [Medline].

  14. Gomez-Tortosa E, Gonzalo I, Fanjul S, et al. Cerebrospinal fluid markers in dementia with lewy bodies compared with Alzheimer disease. Arch Neurol. Sep 2003;60(9):1218-22. [Medline].

  15. Graeber MB, Muller U. Dementia with Lewy bodies: disease concept and genetics. Neurogenetics. Aug 2003;4(4):157-62. [Medline].

  16. Kaufer DI. Pharmacologic treatment expectations in the management of dementia with Lewy bodies. Dement Geriatr Cogn Disord. 2004;17 Suppl 1:32-9. [Medline].

  17. Marti MJ, Tolosa E, Campdelacreu J. Clinical overview of the synucleinopathies. Mov Disord. Sep 2003;18 Suppl 6:S21-7. [Medline].

  18. McKeith I, Del Ser T, Spano P, et al. Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study. Lancet. Dec 16 2000;356(9247):2031-6. [Medline].

  19. McKeith I, Mintzer J, Aarsland D, et al. Dementia with Lewy bodies. Lancet Neurol. Jan 2004;3(1):19-28. [Medline].

  20. McKeith IG, Ince P, Jaros EB, et al. What are the relations between Lewy body disease and AD?. J Neural Transm Suppl. 1998;54:107-16. [Medline].

  21. Miyasaki JM, Shannon K, Voon V, et al. Practice Parameter: Evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. Apr 2 2006;[Medline].

  22. Pasquier F, Delacourte A. Non-Alzheimer degenerative dementias. Curr Opin Neurol. Oct 1998;11(5):417-27. [Medline].

  23. Perry R, McKeith I, Perry E. Dementia with Lewy bodies: The second most common cause of dementia?. Neuroscience News. 1998;1:28-35.

  24. Small GW. Neuroimaging as a diagnostic tool in dementia with Lewy bodies. Dement Geriatr Cogn Disord. 2004;17 Suppl 1:25-31. [Medline].

  25. Wilcock GK. Dementia with Lewy bodies. Lancet. Nov 22 2003;362(9397):1689-90. [Medline].

  26. Wild R, Pettit T, Burns A. Cholinesterase inhibitors for dementia with Lewy bodies. Cochrane Database Syst Rev. 2003;CD003672. [Medline].

Further Reading

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 sleep disorder, myoclonus, apolipoprotein genotype E subtype 4, apoE4 genotype

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: Pfizer Honoraria for Speaking and teaching; Myriad Honoraria for 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 for Speaking and teaching; Bayer Shering Pharma AG Honoraria for Consulting; Boehringer Ingelheim France Honoraria for Consulting; Centapharm Honoraria for Speaking and teaching; Genzyme Corporation Honoraria for Consulting; GlaxoSmithKline Honoraria for Consulting; IMPAX Laboratories, Inc. Honoraria for Consulting; Kyowa Pharmaceuticals, Inc. Honoraria for Consulting; Novartis Pharmaceuticals Corp. Honoraria for Consulting; Prestwick Pharmaceuticals, Inc. Honoraria for Consulting; Schering Plough Honoraria for Consulting; Solvay Pharmeceuticals Honoraria for Consulting; Teva Neuroscience Honoraria for Speaking and teaching

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose

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

CME Editor

Matthew J Baker, MD, Consulting Staff, Collier Neurologic Specialists, Naples Community Hospital
Matthew J Baker, MD is a member of the following medical societies: American Academy of Neurology
Disclosure: Nothing to disclose

Chief Editor

Helmi L Lutsep, MD, Professor, Department of Neurology, Oregon Health and 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 for Review panel membership; Talecris Consulting fee for Review panel membership; AGA Medical Consulting fee for Review panel membership; Boehringer Ingelheim Honoraria for Speaking and teaching; Boston Scientific Honoraria for Speaking and teaching; Concentric Medical None for Review panel membership; Northstar Neuroscience Consulting fee for Review panel membership; ev3 Consulting fee for Review panel membership

 
 
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