Dementia with Lewy bodies
Dementia with Lewy bodies is now the preferred term, but this condition has previously been, and still is, referred to as cortical Lewy body disease, Lewy body dementia, senile dementia of the Lewy body type, and Lewy body variant of Alzheimer's disease.
The characteristic clinical picture is that of a cognitive impairment which precedes or follows closely a symmetrical Parkinsonian syndrome. Tremor is rare compared with classical brainstem Lewy body Parkinson's disease. The cognitive impairment is similar to Alzheimer's disease, except that visual memory and visuoperceptual and visuospatial impairments are more prominent. The additional striking feature is marked fluctuation of cognitive function which can appear as a confusional state with impairment of attention. Reduplicative paramnesias and hallucinations complete the picture. In between these periods of worsening cognition, caregivers will often report episodes of lucidity. Hallucinations also occur late in Alzheimer's disease, however, if present at an early and mild stage, this is a strong indicator of an underlying diagnosis of dementia with Lewy bodies (Ballard et al. 1999). The features have been formalized into criteria in which two out of three of a Parkinsonian syndrome, fluctuations, and hallucinations are required to be present (McKeith et al. 1996). Sleep disturbance is common and myoclonus may be observed. In some patients, the disorder is of an apparent subacute onset with rapid deterioration. A characteristic feature is marked sensitivity to neuroleptics.
The EEG usually shows slowing. Magnetic resonance imaging may show atrophy with relative greater involvement of the parahippocampal gyrus than hippocampus in contrast to Alzheimer's disease (O'Brien et al. 1997).
Functional imaging shows the biparietal bitemporal pattern of Alzheimer's disease, but in addition, more prominent occipital changes which may reflect the visuoperceptual problems and hallucinations (Albin et al. 1996).
The Lewy body in dementia with Lewy bodies is identical to that found in brainstem Lewy body Parkinson's disease, consisting of eosinophilic inclusions on haematoxylin and eosin staining. Recently, α-synuclein has been shown to be a major component of Lewy bodies (Spillantini et al. 1997) and immunohistochemistry not only shows the widespread distribution of Lewy bodies but also neuritic change in affected cells, so-called Lewy neurites (Fig. 1). Lewy bodies are found predominantly in the parahippocampal and entorhinal cortex. Many cases have associated β-amyloid plaques, but typically without the extensive tau-positive neuritic change found in Alzheimer's disease. However, 50% of cases will have neurofibrillary tangles, and although the distribution is somewhat different from Alzheimer's disease, there is clearly overlap of these disorders.
Fig. 1. Photomicrograph showing a Lewy body in the insular cortex; α-synuclein immunohistochemistry (antibody by courtesy of Professor BH Anderton), magnification 900. (Courtesy of Dr T. Revesz.)
Management is notoriously difficult. Treatment of the Parkinsonian syndrome will worsen the confusional state. Patients are exquisitely sensitive to neuroleptics, which not only precipitate a profound extrapyramidal syndrome but also result in worsening cognition. There is some evidence that the atypical neuroleptics such as olanzapine and risperidone may be safer, but even here, there is a risk of worsening the clinical state and, in general, all such drugs should be avoided if at all possible. In early trials of acetylcholinesterase inhibitors, there was a suggestion that patients with dementia with Lewy bodies may respond. Autopsy studies have demonstrated a cholinergic deficit comparable to or even greater than that found in Alzheimer's disease. A recent preliminary report of the acetylcholinesterase inhibitor rivastigmine suggests that this may prove to be a useful line of treatment for managing the hallucinations and confusional state.