Distinguishing Lewy Body from Alzheimer’s Dementia
abstracts & commentary
Source: Hashimoto M, et al. Medial temporal and whole-brain atrophy in dementia with Lewy bodies. Neurology 1998;51:357-362; Boeve BF, et al. REM sleep behavior disorder and degenerative dementia. An association likely reflecting Lewy body disease. Neurology 1998;51:363-370.
Consensus guidelines for the diagnosis of Dementia with Lewy bodies (DLB) (McKeith IG, et al. Neurology 1996;47:1113-1124) delineates certain features that are frequently associated with DLB, such as the early occurrence of parkinsonism without tremor, waxing and waning confusion, hallucinosis, and increased neuroleptic sensitivity—all in the context of progressive cognitive decline. Nevertheless, current clinical criteria are said to fail to identify 25% or more of true cases. Three recent studies provide insight into other features that could ultimately prove useful in the differential diagnosis of DLB.
Olichney et al (Olichney JM, et al. Neurology 1998;51(2):351-357) analyzed data from the USCD Alzheimer’s Disease Research Center and the Consortium to Establish a Registry for AD (CERAD) to determine the rate of decline on the Minimental state examination of patients with autopsy proven Alzheimer’s Disease (AD) (u = 148) vs. the Lewy body variant of AD (LBV) (u = 40). LBV as defined by Olichney et al includes patients with dementia who met neuropathologic criteria for AD but also had one or more Lewy bodies present in the brainstem or cerebral cortex. Analysis of change scores on the MMSE over a five-year period showed a faster rate of decline among the LBV patients, who declined an average of 1.6 MMSE points per year more than the AD patients. The survival time of the LBV groups also appeared shorter, with LBV patients dying an average of 1.6 years earlier than AD patients. Although previous case reports and clinical series have shown similar effects, this is reported to be the first autopsy-proven study of LBV to demonstrate faster cognitive decline.
It has been reported that neuronal cell counts in the hippocampus of patients with DLB are closer to normal than in AD patients. Hashimoto and colleagues used MRI volumetry to determine hippocampal volumes in 27 normals, 27 patients with DLB, and 27 age- and gendermatched patients with AD of comparable severity. They found that average hippocampal volumes in DLB were significantly greater than in AD but less than in normals. Hashimoto et al suggest that this is consistent with previous reports of less severe glucose hypometabolism in the medial temporal lobe and less severe declarative memory impairment in DLB patients compared to AD patients.
Boeve and associates studied 37 patients with degenerative dementia and a history of sleep-associated vigorous movements of the arms and legs with vocalization and dream recall, comprising symptoms of a REM sleep behavior disorder. They found that the sleep disorder preceded or began concurrently with the dementia in all but two cases. The mean age of onset on sleep disturbance was 61.5 years, whereas the onset of cognitive disturbances was, on average, age 68.1. Ninety-two percent of the patients met current criteria for a diagnosis of DLB. Three patients in this series came to autopsy and all had Lewy bodies within the limbic system. Boeve et al expressed the belief that the combination of REM behavioral disturbances and degenerative dementia most likely reflects underlying DLB, although they concede that similar findings may be associated with other disorders.
DLB is reportedly the second most common form of neurodegenerative dementia after AD. DLB is important to recognize and distinguish from AD because its management poses distinct challenges to clinicians as well as caregivers. For example, DLB patients can experience fixed delusions and visual hallucinosis early in the course of their illness, and these patients may develop dramatic worsening of their extrapyramidal symptoms when treated with neuroleptics. DLB patients may respond favorably to acetylcholinesterase inhibitors.
Neither rate of progression of cognitive decline, hippocampal volume loss, nor an association with REM sleep disturbances are likely to become major new diagnostic criteria for DLB. Nevertheless, eliciting a history of an antecedent REM sleep disturbance, seeing a less than expected degree of hippocampal atrophy, or observing a more rapid than expected rate of cognitive decline might serve to trigger reconsideration of the patient having DLB rather than AD. The current means for distinguishing AD from DLB need to be improved upon and further studies using larger cohorts of demented patients are needed.