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Abstract & Commentary
Source: Harding AJ, et al. Brain. 2002;125:391-403.
The pathologic hallmark of Parkinson’s disease (PD) is the accumulation of Lewy bodies within the substantia nigra. Improvements in immunohistochemistry in the last decade have revealed that Lewy bodies are often abundant in the cerebral cortex as well as the midbrain. Investigators have tried to separate patients with PD, Parkinson’s disease with late developing dementia (PDD), and dementia with Lewy bodies (DLB) based on their clinical features, emphasizing the presence of fluctuating cognition and visual hallucinations in DLB, and the late development of dementia in PDD. In fact, there is considerable overlap between DLB and PDD, and it is often difficult to differentiate patients with PD who have hallucinations and mild cognitive impairment from those with developing DLB.
One might ask why neurologists should be concerned about these distinctions at all. In fact, the presence of cognitive decline and formed persistent visual hallucinations is an ominous clinical feature for patients and their families, often leading to permanent assistance in the home or even placement in a nursing home. Protecting Parkinson patients from paranoid ideation or frightening visual hallucinations is one of the most important responsibilities of neurologists who care for patients with that disease.
The present study reflects a comprehensive, prospective, clinico-pathologic correlation of parkinsonian features with pathologic findings in a cohort of patients studied in Australia. Harding and colleagues prospectively examined patients using a wide variety of clinical rating instruments to assess motor performance, cognition, behavior, and the nature of visual hallucinations. After death, brains were examined for the presence and density of cortical Lewy bodies.
The majority of DLB and PDD cases had visual hallucinations early in their course, whereas less than one quarter of PD cases had hallucinations. Cognitive fluctuations were present in most DLB cases, and significantly less frequently in PDD and PD. However, neither visual hallucinations nor cognitive fluctuations were predictive of DLB, although their absence early in the disease course was highly suggestive of PD.
The highest density of cortical Lewy bodies in DLB occurred in the amygdala, anterior cingulate, inferior temporal, and parahippocampal regions. The sum of combined density of Lewy bodies in the cortex did not correlate with the severity of dementia. Lewy bodies in the parahippocampus and inferior temporal cortex were highly predictive of formed visual hallucinations.
This study is one of the most comprehensive attempts to correlate clinical and pathologic features in patients with Lewy body pathology. The primary finding that formed visual hallucinations suggest Lewy body pathology in the inferior temporal cortex, is the first association between visual hallucinations and cortical pathology. The study also demonstrates the clinical and pathologic overlap between patients with DLB and PDD. Although this issue is still subject to debate, the present study supports the idea that PD, PDD, and DLB represent different points on a pathologic continuum characterized by accumulation of Lewy bodies within the brain. —Steven Frucht
Dr. Frucht, Assistant Professor of Neurology, Movement Disorders Division, Columbia-Presbyterian Medical Center, is Assistant Editor of Neurology Alert.