Nigral pathology and Parkinsonian signs in elders without Parkinson disease

Rush Alzheimer's Disease Center, Chicago, IL, USA.
Annals of Neurology (Impact Factor: 9.98). 02/2012; 71(2):258-66. DOI: 10.1002/ana.22588
Source: PubMed


Motor symptoms such as mild parkinsonian signs are common in older persons, but little is known about their underlying neuropathology. We tested the hypothesis that nigral pathology is related to parkinsonism in older persons without Parkinson disease (PD).
More than 2,500 persons participating in the Religious Orders Study or the Memory and Aging Project agreed to annual assessment of parkinsonism with a modified version of the Unified Parkinson Disease Rating Scale and brain donation. Brains from 744 deceased participants without PD were assessed for nigral neuronal loss and α-synuclein immunopositive Lewy bodies.
Mean age at death was 88.5 years. Mean global parkinsonism was 18.6 (standard deviation, 11.90). About ⅓ of cases had mild or more severe nigral neuronal loss, and about 17% had Lewy bodies. In separate regression models that adjusted for age, sex, and education, nigral neuronal loss and Lewy bodies were both related to global parkinsonism (neuronal loss: estimate, 0.231; standard error [SE], 0.068; p < 0.001; Lewy bodies: estimate, 0.291; SE, 0.133; p = 0.029). Employing a similar regression model that included both measures, neuronal loss remained associated with global parkinsonism (neuronal loss: estimate, 0.206; SE, 0.075; p = 0.006). By contrast, the association between Lewy bodies and global parkinsonism was attenuated by >60% and was no longer significant (Lewy bodies: estimate, 0.112; SE, 0.148; p = 0.447), suggesting that neuronal loss may mediate the association of Lewy bodies with global parkinsonism.
Nigral pathology is common in persons without PD and may contribute to loss of motor function in old age.

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Available from: Sukriti Nag
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    • "These observations led to the Braak hypothesis, which defines PD as a neurodegenerative diseases that ascends from the dorsal motor nucleus of the vagus nerve, to lower brainstem areas including the ventral midbrain, and finally to neocortical regions[9]. However, the presence of Lewy bodies alone does not explain the onset and progression of PD[10], indicating that a secondary effect triggered by neuronal impairment might be responsible for its progressive nature. Neuroinflammatory reactions have been described in virtually all PD cases, with several studies supporting the hypothesis that microglia-mediated neuroinflammatory responses exacerbate the loss of mDA neurons and, thus, worsen the clinical symptoms[11,12]. "
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