Lewy Body Dementia: Case Report and Discussion

Natan Khotianov, MD, Ranjit Singh, MBBChir, MA(Cantab), Sonjoy Singh MBBChir, MA(Cantab)

Disclosures

J Am Board Fam Med. 2002;15(1) 

In This Article

Discussion

Lewy body dementia is named after the German physician Fritz Heinrich Lewy, who at the beginning of the 20th century first described distinctive extranuclear inclusions on microscopic brain tissue examination. These inclusions became known as Lewy bodies. It was not until the latter part of the 20th century that the importance of these lesions began to be recognized. Initially, a subgroup of Alzheimer disease patients was determined to have characteristic pathologic findings of cortical or brainstem Lewy bodies at autopsy.[1,2] Later it became clear that these patients with Lewy bodies constituted a distinct neuropathologic and clinical entity, which became known as dementia with Lewy bodies or Lewy body dementia.[4] Various subtypes have been described based on pathologic findings, details of which can be found in the literature.[4,5]

The disease is more common in men than women with a ratio of 2:1. The mean age at onset of symptoms i 68 years. The average time from onset to death is 6.4 years, with the most frequent cause of death being aspiration pneumonia. The cause of Lewy body dementia remains unknown. Some speculate that genetics plays a role, and studies are underway to investigate this possibility. It remains to be seen whether genetic testing will ever be sufficiently sensitive and specific to help in the clinical diagnosis of Lewy body dementia.

Currently, definitive diagnosis of Lewy body dementia can be made only at autopsy. Clinically, as illustrated by this case, there is considerable overlap between Lewy body dementia and both Alzheimer disease and Parkinson disease. To improve the sensitivity and specificity of the clinical diagnosis, a set of clinical criteria for Lewy body dementia was drafted in 1996 by the Consortium on Dementia with Lewy Bodies.[4] To diagnose Lewy body dementia using these criteria, there must be progressive cognitive decline that interferes with normal social or occupational functioning. Memory and visuospatial deficits are often, but not necessarily, prominent. In addition, two of the following three features must also be present: recurrent visual hallucinations[6] (which are typically well detailed), fluctuating cognition, and spontaneous motor features of parkinsonism. Supportive of the diagnosis are repeated falls, syncope, transient loss of consciousness, systematized delusions, neuroleptic sensitivity, and hallucinations in other sensory modalities. The absence of stroke, focal neurological signs, and delirium makes the diagnosis of Lewy body dementia more likely.

These clinical criteria, when compared with the reference standard of autopsy, have been found to be highly specific (specificity 79%-100%) but to lack sensitivity (sensitivity 22%-75%.),[7] implying that these criteria are useful for confirming the diagnosis but cannot be relied on for screening. This limitation of the clinical criteria is due at least to the following two factors. First, there is considerable overlap between the features of Lewy body dementia and those of other dementias. Second, the characteristic or diagnostic features of Lewy body dementia frequently do not become manifest until a late stage in the disease. Given the high prevalence of Lewy body dementia and its unique implications for management, the prudent primary care physician must be particularly alert for this diagnosis. As for any dementia, a thorough history (including interviews with family members and caregivers) and physical, neurological, and cognitive examinations are essential.

Although there is considerable interest in the role of functional imaging techniques designed to distinguish Lewy body dementia form Alzheimer disease, these techniques are not available for routine use. Essentially, radioisotope scans reflect either regional blood ow,[8] regional glucose metabolism,[9] or dopaminergic neuronal degeneration.[10] It is hoped that these types of imaging studies will eventually become widely available for definitive antemortem diagnosis.

Perhaps the most clinically important feature of Lewy body dementia is the tendency for neuroleptic sensitivity. Studies suggest that about 50% of patients develop severe extrapyramidal symptoms, such as rigidity, altered consciousness, pyrexia, and collapse when exposed to neuroleptic agents. That these reactions can be irreversible and sometimes fatal[11,12] has important implications for the management of psychotic symptoms in these patients. Other strategies for managing these symptoms should be exhausted before resorting to medications; when neuroleptics are necessary, it might be wise to consider admission to the hospital for dose titration. There is some debate in the literature[13,14] about whether atypical neuroleptics, such as risperidone and quetiapine, might provide useful antipsychotic effects in Lewy body dementia without causing substantial extrapyramidal side effects, but this possibility has not been thoroughly investigated.

Despite the parkinsonian features, many patients with Lewy body dementia exhibit limited clinical response to L-dopa. Further, it should be noted that L-dopa can cause or exacerbate visual hallucinations, which tend to occur in these patients. For patients with Lewy body dementia, therefore, the risks of treatment with L-dopa will frequently outweigh the benefits. A possible explanation for the limited response to L-dopa lies in the finding that, compared with patients with Parkinson disease, those with Lewy body dementia have a lower density of dopamine D2 receptors in the corpus striatum.[15] This finding might also explain the increased sensitivity to neuroleptics, which are dopamine antagonists.

A few studies have examined the effects of cholinesterase inhibitors (including donepezil and rivastigmine) in patients with Lewy body dementia. The main outcomes studied were hallucinations, behavior, and cognition. In two case series[16,17] where donepezil was used for 8 to 24 weeks at doses of 5 to 10 mg, there was a decrease in the frequency and duration of hallucinations. One of these series[17] also found an improvement in cognition (mean increase in MMSE score of 4.4 in 7 of 9 patients). The response to donepezil observed in our patient was thus consistent with previously reported findings but was rather more dramatic than would typically be expected. Studies of rivastigmine include an open trial[18] and a randomized double-blind placebo-controlled study.[19] Doses ranged from 3-12 mg/d. Findings after 12 to 20 weeks of treatment included decreased hallucinations and delusions, improved behavior, and in the latter study[19] a trend (not statistically significant) toward improved cognition. Although further studies are needed, the current evidence suggests that the cholinesterase inhibitors might have an important role to play in the management of Lewy body dementia.

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