Dementia with Lewy Bodies

 

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ABSTRACT

Synucleinopathies, with and without dementia, encompass a wide range of diseases including Parkinson's disease, multiple system atrophy, rapid eye movement (REM) sleep behavior disorder, and dementia with Lewy bodies (DLB). DLB is a neurodegenerative disorder resulting in slowly progressive and unrelenting dementia until death. Prevalence studies suggest that it is the second most common dementing illness in the elderly. The neuropathologic findings of DLB show a wide anatomic range. Lewy bodies and Lewy-related pathology are found from the brain stem to the cortex and, in many cases, associated with concurrent Alzheimer's disease pathology. A recent international consortium on DLB has resulted in revised criteria for the clinical and pathological diagnosis of DLB incorporating new information about the core clinical features and improved methods for their assessment. The presentation of DLB is typically one of cortical and subcortical cognitive impairments, with worse visuospatial and executive dysfunction than Alzheimer's disease. There may be relative sparing of memory especially in the early stages. Core clinical features of DLB include fluctuating attention, recurrent visual hallucinations, and parkinsonism. Suggestive features include REM sleep behavior disorder, severe neuroleptic sensitivity, and low dopamine transporter uptake in the basal ganglia on functional neuroimaging. Additional supportive features that commonly occur in DLB, but with lower specificity, include repeated falls and syncope, transient, unexplained loss of consciousness, severe autonomic dysfunction, hallucinations in other modalities, systematized delusions, depression, relative preservation of medial temporal lobe structures on structural neuroimaging, reduced occipital activity on functional neuroimaging, prominent slow wave activity on electroencephalogram, and low uptake myocardial scintigraphy. Management of DLB includes pharmacological and nonpharmacological interventions for its cognitive, neuropsychiatric, motor, and sleep disturbances.

REFERENCES

• 1 Hansen L A, Samuel W. Criteria for Alzheimer's disease and the nosology of dementia with Lewy bodies.  Neurology. 1997;  48 126-132
  PubMedGoogle Scholar
• 2 Lewy F H. Handbuch der Neurologie. Berlin; Springer 1912
  Google Scholar
• 3 Kosaka K, Yoshimura M, Ikeda K, Budka H. Diffuse type of Lewy body disease: progressive dementia with abundant cortical Lewy bodies and senile changes of varying degree-a new disease?.  Clin Neuropathol. 1984;  3 185-192
  PubMedGoogle Scholar
• 4 Polymeropoulos M H, Lavedan C, Leroy E et al.. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease.  Science. 1997;  276 2045-2047
  PubMedGoogle Scholar
• 5 Spillantini M G, Schmidt M L, Lee V M, Trojanowski J Q, Jakes R, Goedert M. Alpha-synuclein in Lewy bodies.  Nature. 1997;  388 839-840
  CrossrefPubMedGoogle Scholar
• 6 Dawson T M, Dawson V L. Molecular pathways of neurodegeneration in Parkinson's disease.  Science. 2003;  302 819-822
  CrossrefPubMedGoogle Scholar
• 7 Galvin J E, Lee V M, Trojanowski J Q. Synucleinopathies: clinical and pathological implications.  Arch Neurol. 2001;  58 186-190
  CrossrefPubMedGoogle Scholar
• 8 Kotzbauer P T, Trojanowsk J Q, Lee V M. Lewy body pathology in Alzheimer's disease.  J Mol Neurosci. 2001;  17 225-232
  PubMedGoogle Scholar
• 9 Minoshima S, Foster N L, Petrie E C, Albin R L, Frey K A, Kuhl D E. Neuroimaging in dementia with Lewy bodies: metabolism, neurochemistry, and morphology.  J Geriatr Psychiatry Neurol. 2002;  15 200-209
  PubMedGoogle Scholar
• 10 Colosimo C, Hughes A J, Kilford L, Lees A J. Lewy body cortical involvement may not always predict dementia in Parkinson's disease.  J Neurol Neurosurg Psychiatry. 2003;  74 852-856
  CrossrefPubMedGoogle Scholar
• 11 Merdes A R, Hansen L A, Jeste D V et al.. Influence of Alzheimer pathology on clinical diagnostic accuracy in dementia with Lewy bodies.  Neurology. 2003;  60 1586-1590
  PubMedGoogle Scholar
• 12 McKeith I G, Dickson D W, Lowe J et al.. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium.  Neurology. 2005;  65 1863-1872
  CrossrefPubMedGoogle Scholar
• 13 Lauterbach E C. The neuropsychiatry of Parkinson's disease.  Minerva Med. 2005;  96 155-173
  PubMedGoogle Scholar
• 14 Hurtig H I, Trojanowski J Q, Galvin J et al.. Alpha-synuclein cortical Lewy bodies correlate with dementia in Parkinson's disease.  Neurology. 2000;  54 1916-1921
  PubMedGoogle Scholar
• 15 Aarsland D, Perry R, Brown A, Larsen J P, Ballard C. Neuropathology of dementia in Parkinson's disease: a prospective, community-based study.  Ann Neurol. 2005;  58 773-776
  CrossrefPubMedGoogle Scholar
• 16 McKeith I G, 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. 1996;  47 1113-1124
  CrossrefPubMedGoogle Scholar
• 17 McKeith I G, Ballard C G, Perry R H et al.. Prospective validation of consensus criteria for the diagnosis of dementia with Lewy bodies.  Neurology. 2000;  54 1050-1058
  PubMedGoogle Scholar
• 18 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;  16 229-237
  CrossrefPubMedGoogle Scholar
• 19 Tiraboschi P, Salmon D P, Hansen L A, Hofstetter R C, Thal L J, Corey-Bloom J. What best differentiates Lewy body from Alzheimer's disease in early-stage dementia?.  Brain. 2006;  129 729-735
  CrossrefPubMedGoogle Scholar
• 20 Briel R C, McKeith I G, Barker W A et al.. EEG findings in dementia with Lewy bodies and Alzheimer's disease.  J Neurol Neurosurg Psychiatry. 1999;  66 401-403
  PubMedGoogle Scholar
• 21 Ferman T J, Smith G E, Boeve B F et al.. DLB fluctuations: specific features that reliably differentiate DLB from AD and normal aging.  Neurology. 2004;  62 181-187
  CrossrefPubMedGoogle Scholar
• 22 Harding A J, Broe G A, Halliday G M. Visual hallucinations in Lewy body disease relate to Lewy bodies in the temporal lobe.  Brain. 2002;  125 391-403
  CrossrefPubMedGoogle Scholar
• 23 McKeith I G, Wesnes K A, Perry E, Ferrara R. Hallucinations predict attentional improvements with rivastigmine in dementia with Lewy bodies.  Dement Geriatr Cogn Disord. 2004;  18 94-100
  CrossrefPubMedGoogle Scholar
• 24 Molloy S, McKeith I G, O'Brien J T, Burn D J. The role of levodopa in the management of dementia with Lewy bodies.  J Neurol Neurosurg Psychiatry. 2005;  76 1200-1203
  CrossrefPubMedGoogle Scholar
• 25 McKeith I G, Perry R H, Fairbairn A F, Jabeen S, Perry E K. Operational criteria for senile dementia of Lewy body type (SDLT).  Psychol Med. 1992;  22 911-922
  PubMedGoogle Scholar
• 26 Walker Z, Costa D C, Walker R W et al.. Striatal dopamine transporter in dementia with Lewy bodies and Parkinson disease: a comparison.  Neurology. 2004;  62 1568-1572
  PubMedGoogle Scholar
• 27 Taki J, Yoshita M, Yamada M, Tonami N. Significance of 123I-MIBG scintigraphy as a pathophysiological indicator in the assessment of Parkinson's disease and related disorders: it can be a specific marker for Lewy body disease.  Ann Nucl Med. 2004;  18 453-461
  PubMedGoogle Scholar
• 28 Litvan I, MacIntyre A, Goetz C G et al.. Accuracy of the clinical diagnoses of Lewy body disease, Parkinson disease, and dementia with Lewy bodies: a clinicopathologic study.  Arch Neurol. 1998;  55 969-978
  CrossrefPubMedGoogle Scholar
• 29 Galasko D. Cerebrospinal fluid biomarkers in Alzheimer disease: a fractional improvement?.  Arch Neurol. 2003;  60 1195-1196
  CrossrefPubMedGoogle Scholar
• 30 Touchon J, Bergman H, Bullock R, Rapatz G, Nagel J, Lane R. Response to rivastigmine or donepezil in Alzheimer's patients with symptoms suggestive of concomitant Lewy body pathology.  Curr Med Res Opin. 2006;  22 49-59
  CrossrefPubMedGoogle Scholar
• 31 Molloy S, McKeith I G, O'Brien J T, Burn D J. The role of levodopa in the management of dementia with Lewy bodies.  J Neurol Neurosurg Psychiatry. 2005;  76 1200-1203
  CrossrefPubMedGoogle Scholar
• 32 Aarsland D, Mosimann U P, McKeith I G. Role of cholinesterase inhibitors in Parkinson's disease and dementia with Lewy bodies.  J Geriatr Psychiatry Neurol. 2004;  17 164-171
  CrossrefPubMedGoogle Scholar

David WeismanM.D. 

University of California, San Diego Alzheimer's Disease Research Center

9500 Gilman Drive, La Jolla, CA 92093