M. Otto
Epidemiology
Lewy body dementia (LBD) is still an underdiagnosed disease. Recent studies suggest that, at 15–35% of cases, it is the second most common form of dementia after Alzheimer's disease (McKeith et al., 2000).
Clinical Features
Core symptoms. The core symptoms are (Table 11.4):
• Distinct fluctuations in cognitive abilities, particularly in attention.
• Visual hallucinations.
• Spontaneous extrapyramidal motor symptoms.
In addition, recurrent falls, syncope, depression, REM sleep behavior disorder, and pronounced sensitivity to treatment with neuroleptics are often seen.
Fluctuations. One of the core symptoms of LBD is the fluctuation of cognitive deficits and attention. Due to the parkinsonian symptoms, the diagnosis is often Parkinson's disease or Parkinson's disease with dementia. For differential diagnosis, it is suggested that if dementia occurs within 12 months alongside parkinsonian symptoms, a diagnosis of LBD should be made. Creutzfeldt-Jakob disease is frequently considered in the differential diagnosis on the basis of the rapid development and the additional focal neurological symptoms.
Diagnosis
CSF analysis. Elevated tau protein levels and decreased Aβ peptide1–42 levels may be found. Therefore, these markers do not permit a distinction between LBD and Alzheimer's disease in any given case. Recently, it has been reported that elevated levels of heart-type fatty-acid-binding protein (h-FABP) were detected in the serum of LBD patients. In a small study, this marker distinguished between Alzheimer's disease and LBD (Steinacker et al., 2004). It should be pointed out that the elevation of this marker may imply cardiac involvement in the development of LBD; at least this supposition is confirmed by some neuropathological investigations.
Although no LBD-specific genetic markers have been identified, LBD, like Alzheimer's disease, occurs more frequently in patients carrying the ApoE ε4 allele.
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Table 11.4 Consensus guidelines for the clinical diagnosis of Lewy body dementia (LBD) (McKeith et al., 2000) |
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Central features required for diagnosis of LBD |
• Progressive cognitive decline of suficient magnitude to interfere with normal social and occupational function • Prominent or persistent memory impairment does not necessarily occur in the early stages but becomes evident with progression of the disease • Deficits may become prominent on tests of attention, frontal subcortical skills, and visuospatial ability |
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Core features • Two core features are essential for a diagnosis of probable LBD • One core feature is essential for a diagnosis of possible LBD |
• Fluctuating cognition with pronounced variations in attention and alertness • Recurrent visual hallucinations that are typically well formed and detailed • Spontaneous extrapyramidal motor symptoms of parkinsonism |
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Features supporting a diagnosis of LBD |
• Repeated falls • Syncope • Transient loss of consciousness • Neuroleptic hypersensitivity • Systematized delusions • Hallucinations in other modalities • REM sleep behavior disorder • Depression |
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Features making a diagnosis of LBD less likely (negative features) |
• Distinct vascular lesions, e. g., focal neurological signs or lesions on CT or MRI • Signs of other diseases that may be responsible for the clinical picture |
Neuroimaging. CT and MRI may reveal generalized atrophy with prominent changes in the frontal lobe.
Neuropathology. The disease is characterized by eosinophilic cytoplasmic inclusions called Lewy bodies. During the further course of the disease, Lewy bodies are found not—as in Parkinson's disease—in the brain stem alone, but also in the cortex and neocortex. Lewy bodies are easily detected by immunohistochemical staining for α-synuclein, a protein constituent of Lewy bodies. Apart from these Lewy bodies, the pathology is to a variable extent typical of Alzheimer's disease; this is in agreement with the neuropathological diagnostic criteria for LBD.
References
McKeith IG, Ballard CG, Perry RH, et al. Prospective validation of consensus criteria for the diagnosis of dementia with Lewy bodies. Neurology 2000;54:1050–1058
Steinacker P, Mollenhauer B, Bibl M, et al. Heart fatty acid binding protein as a potential diagnostic marker for neurodegenerative diseases. Neurosci Lett 2004;370:36–39
Further Reading
Holmes C, Cairns N, Lantos P, Mann A. Validity of current clinical criteria for Alzheimer's disease, vascular dementia and dementia with Lewy bodies. Br J Psychiatry 1999;174:45–50
Kretzschmar HA, Neumann M. Neuropathological diagnosis of neurodegenerative and dementia diseases. Pathologe 2000;21:364–374
Mc Keith IG, Mintzer J, Aarsland D, et al. Dementia with Lewy bodies. Lancet Neurol 2004;3:19–28
Merdes AR, Hansen LA, Jeste DV, et al. Influence of Alzheimer pathology on clinical diagnostic accuracy in dementia with Lewy bodies. Neurology 2003;60:1586–1590
Spillantini MG, Schmidt ML, Lee VM, et al. Alpha-synuclein in Lewy bodies. Nature 1997;388:39–40