Accuracy of the Clinical Diagnoses of Lewy Body Disease, Parkinson Disease, and Dementia With Lewy Bodies

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Abstract
CONTROVERSY exists as to whether Parkinson disease (PD) and dementia with Lewy bodies (DLB), including diffuse Lewy body disease and a Lewy body variant of Alzheimer disease (AD),1 represent 2 distinct nosologic entities or whether they exist along the spectrum of a single disorder, Lewy body disease.2-7 Such debate is the logical consequence of the considerable overlap of clinical and neuropathologic features in disorders associated with Lewy bodies. For example, extrapyramidal features may be found in many patients with severe AD8,9 and dementia in many patients with PD.10,11 As yet, there are no clinical markers for these neurodegenerative diseases, thus necessitating neuropathologic examination for their definitive diagnosis. Pathologically, PD was originally defined by the presence of Lewy bodies, first in the substantia innominata and dorsal motor nucleus of the vagus nerve12 and later in the substantia nigra.13 Not all neurologists agree that Lewy bodies are essential for a diagnosis of PD14 because Lewy bodies are found in healthy elderly individuals,15-21 in patients with dementia but no evidence of parkinsonism,22 in cases of dementia in which parkinsonian syndrome becomes evident in later stages, and in other neurologic disorders.23 Nevertheless, Lewy bodies are more numerous in the brains of patients with PD than in healthy elderly subjects and patients with other neurologic disorders. Pathologic investigation of patients with various presentations of dementia and parkinsonism showed a higher concentration24 and wider distribution of Lewy bodies, extending into the cerebral cortex, subcortical nuclei, and brainstem nuclei.25 Such diverse presentations have been described variously as senile dementia of Lewy body type,26 dementia associated with cortical Lewy bodies,27 Lewy body variant of AD,28 AD with PD changes,29 and diffuse Lewy body disease.3,25,30 All of these terms were recently classified as DLB.1 Despite the presence of Lewy bodies in PD and DLB, the relationship between these disorders remains debatable. Differences in the composition of cortical and nigral Lewy bodies for PD and DLB may lead to an artificial nomenclature based on histological features and not pathogenesis,5,7 and the nonspecificity of Lewy bodies in PD31 may suggest an inappropriate classification of PD as a single disease entity.2,10 These issues, together with the absence of disease markers and clinical overlap with other diseases, including multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), challenge clinicians to make an early and accurate clinical diagnosis in patients with parkinsonian symptoms.