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condition have been increasing steadily since the original communication by Okazaki and others in 1961 (see review by Kosaka) The disease is marked by parkinsonian features, dementia, and a frequent tendency to episodic delirium, as described below The syndrome may be clinically indistinguishable from Alzheimer disease, but it is de ned by diffuse involvement of cortical neurons with Lewy body inclusions and by an absence or inconspicuous number of neuro brillary tangles and senile plaques To some extent increased recognition of this disorder is due to improved histologic techniques, particularly the ability to detect ubiquitin by immunostaining and, more recently, similar stains for synuclein, which enable one to visualize Lewy bodies in the cerebral cortex more clearly than had been possible in the past Because the Lewy bodies in cortical neurons are not surrounded by a distinct halo, as they are in the substantia nigra in cases of Parkinson disease, they were not readily appreciated until the development of these antibody stains The fact that aggregated -synuclein is the main component of the Lewy body will undoubtedly prove important in understanding both Parkinson disease and Lewy body dementia Clinical Features Burkhardt and colleagues, in an analysis of 34 cases of diffuse Lewy body disease, found that the characteristic syndrome was one of progressive dementia in an elderly patient with the late onset of parkinsonian signs in some cases For this reason, the disease also properly belongs in the category of dementias that are accompanied by other prominent neurologic features (page 897) Dif culty in diagnosis arises because the movement disorder may be either mild or prominent and may occur as an early or a late manifestation In Lennox s summary of 75 cases published up to 1990, parkinsonism, and particularly a limb and axial rigidity, was a prominent feature in 90 percent once the illness was fully developed, and almost half had tremor of the Parkinson type The parkinsonian features may respond favorably to L-dopa, but only for a limited time and sometimes at the expense of delirium or hallucinations that would be uncharacteristic of early idiopathic Parkinson disease (Hely et al); in others, the response to Ldopa is not as consistent Some patients also have orthostatic hypotension corresponding to cell loss and Lewy bodies in the intermediolateral cell column of the spinal cord or in the sympathetic ganglia, thereby simulating striatonigral degeneration or ShyDrager syndrome (see further on) Byrne and associates pointed out that episodic confusion, hallucinations, and paranoid delusions were a feature of the Lewy body dementia; such psychotic features are generally uncharacteristic of Alzheimer and lobar dementias In Lennox s review, onethird of patients had these swings in behavior, but as the illness advanced, the amnesia, dyscalculia, visuospatial disorientation, aphasia, and apraxia did not differ from those of Alzheimer disease In the cases reported by Fearnley and coworkers, there was a supranuclear gaze palsy simulating that of progressive supranuclear palsy In our experience with Lewy body disease, the parkinsonian symptoms have been more prominent than in progressive supranuclear palsy, and the most characteristic feature besides the movement disorder and a slowly advancing dementia has been a vacuous anxious state with intermittent psychotic or delirious behavior Others have commented on an extreme sensitivity of such patients to neuroleptic drugs, including increased confusion and greatly worsening parkinsonism or the development of the neuroleptic malignant syndrome.

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(See also page 906) Focal disturbances, particularly aphasia and apraxia, occur early and prominently in certain patients with Pick-like lobar atrophy, indicating a lesion in the left frontal and/or temporal lobes Viewed from another perspective, a language disorder has been described in two-thirds of all patients with temporal lobe atrophy At rst, the patient speaks less and has word- nding dif culty (anomia), but language structure is intact (Mesulam); later, he may forget and misuse words and soon fails to understand much of what is heard or read Speech becomes a medley of disconnected words and phrases and eventually is reduced to an incomprehensible jargon Later, dysarthria and apraxia become apparent, and nally, the patient is mute, seemingly without impulse to speak, with a complete loss of the ability to form words (Snowden et al) In a less common form, there is early comprehension dif culty followed by verbal perseveration, but uency is retained The above descriptions conform also to what is now called primary progressive aphasia, and it is notable that, according to Mesulam, who has studied the condition extensively, 60 percent of these cases show no characteristic pathologic change, 20 percent have Pick bodies, and a similar proportion show the typical changes of Alzheimer disease in the affected cortical region A familial tendency has not been found

Next to Alzheimer disease, diffuse Lewy body disease, or Lewy body dementia, has been the most frequent pathologic diagnosis established in most series of demented patients Reports of this

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With regard to diagnostic testing, only the nding of reduced activity in the posterior parietal cortical regions on PET scans has been found as a relatively consistent but not invariable feature

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