DEMENTIA WITH LEWY BODIES

Dementia with Lewy bodies is a comparatively new diagnostic entity. Formal criteria for its diagnosis have existed only since 1992. Even now, changes in neuropathological techniques for its recognition are changing the understanding of how commonly this disease occurs. Depending on the study, it may vie with fronto-temporal dementia as the next most common neurodegenerative cause of dementia after Alzheimer's disease.

By definition, patients with Lewy body dementia have progressive cognitive impairment that interferes with their social or occupational functioning. What makes the diagnosis distinctive on a clinical basis is the presence of several features that, though seen in patients with Alzheimer's disease, are seen earlier in patients who have dementia with Lewy bodies. These features include mild, spontaneous Parkinsonism (usually muscle rigidity together with slowness, a tendency to fall, and, less commonly, tremor) and hallucinations. There is also some suggestion that the cognitive features in dementia with Lewy bodies differ subtly from those in Alzheimer's disease, more often showing earlier difficulties with visuospatial function, and attention and concentration.

The pathological hallmark of dementia with Lewy bodies is, of course, the Lewy body, named after the physician who first identified these spherical inclusions within the bodies of neurons. Once comparatively underappreciated, careful observation and development of new techniques have allowed these to be seen more readily. Lewy bodies were long a pathological hallmark for the diagnosis of Parkinson's disease, and in that context were found in neurons deep in the brain known as the substantia nigra. Lewy bodies are not the only abnormal proteins seen in dementia with Lewy bodies, and their exact origin and role are not yet well understood. Of some interest has been the finding that, in neuropathological examination of the brain, pure Lewy body disease remains uncommon. Most cases of dementia with Lewy bodies are seen in patients who also have neuropathological evidence of Alzheimer's disease, and many show injury from the effects of hypertension and stroke.

Clinical features of dementia with Lewy bodies that are more specific for the diagnosis include fluctuation both in the level of arousal and consciousness and in the severity of the symptoms. In these patients, arousal can be so impaired as to mimic stupor or even coma. More commonly, the picture resembles delirium with so-called "clouding of unconsciousness" and fluctuation (i.e., patients can seem vary drowsy, but within several minutes can again become alert, and even hyperalert, before cycling). Whereas in delirium these symptoms are commonly more subtle, in dementia with Lewy bodies they can persist for weeks, months, or longer. Another important and tragic aspect of the clinical picture in dementia with Lewy bodies is the presence of a neuroleptic sensitivity syndrome. Neuroleptics are drugs that typically are used to treat hallucinations, delusions, and other psychotic features. In general, they work by blocking the brain chemical dopamine. In some patients with dementia with Lewy bodies, however, the result of using even modest doses of neuroleptics can be catastrophic. Such patients can experience profound worsening of their Parkinsonism in ways from which they sometimes never recover.

There have been encouraging results, however, in the treatment of dementia with Lewy bodies with the class of drugs known as acetylcholinesterase inhibitors. Originally used for the treatment of Alzheimer's disease, these drugs can sometimes have a particularly favorable response in patients who have dementia with Lewy bodies. As with other dementia patients, there is an important role for symptomatic and supportive treatment, both of the patients and of their caregivers.

It is not yet clear how to interpret the prognosis of dementia with Lewy bodies. In the era prior to cholinesterase inhibitor therapy, particularly when the neuroleptic sensitivity syndrome was poorly understood or uncommonly recognized, the prognosis appeared to be worse than for Alzheimer's disease. How this plays out with the advent of better recognition and treatment is not yet clear.

The recognition and elaboration of the diagnosis of dementia with Lewy bodies is a tribute to careful cooperation among physicians, scientists, patients, and caregivers. Through systematic observation, what was until recently unrecognized as a disease is now seen to be a common form of treatable cognitive impairment in older adults.

Kenneth Rockwood

See also Alzheimer's Disease; Delirium; Demantia; Fronto-Temporal Dementia; Parkinsonism; Vascular Dementia.

BIBLIOGRAPHY

Ballard, C.; O'Brien, J.; Morris, C. M.; Barber, R. Swann, A.; Neill, D.; and McKeith, I. "The Progression of Cognitive Impairment in Dementia with Lewy Bodies, Vascular Dementia and Alzheimer's Disease." International Journal of Geriatric Psychiatry 5 (2000): 499–503.

McKeith, I.; Ballard, C.; Perry, R.; Ince, P.; O'Brien, J.; Neill, D.; Lowery, K.; Jaros, E.; Barber, R.; Thompson, P.; Swann, A.; Fairbairn, A.; and Perry, E. "Prospective Validation of Consensus Criteria for the Diagnosis of Dementia with Lewy Bodies." Neurology 54, no. 5 (2000): 1050–1058.

McKeith, I.; Del Ser, T.; Spano, P.; Emre, M.; Wesnes, K.; Anand, R.; Cicin-Sain, A.; Ferrara, R.; and Spiegel, R. "Efficacy of Riva-stigmine in Dementia with Lewy Bodies: A Randomised Double-Blind, Placebo-Controlled International Study." Lancet 356, no. 9247 (2000): 2031–2036.