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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    • "Having both, SN-hyperechogenicity and hyposmia, was associated with an odds ratio of 3.0 for incident MPS. A recent clinicopathologic study reported SN neuronal loss in one-third and incidental Lewy bodies in one-sixth of community-dwelling elderly and identified nigral pathology as major contributor to the loss of motor function in old age [4]. Accordingly, in our cohort increased SN-echogenicity was found in one-quarter of subjects [8] and we here demonstrate its close relation to the development of MPS, mainly bradykinesia and rigidity. "
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    ABSTRACT: Mild parkinsonian signs (MPS) are common in the elderly population and are associated with a wide range of adverse health outcomes, including incident Parkinson's disease (PD). We aimed to prospectively evaluate potential risk factors for incident MPS. Participants of the population-based Bruneck Study representative for the general elderly community underwent a baseline assessment of substantia nigra (SN)-echogenicity with transcranial sonography, olfactory function with the Sniffin' Sticks identification test and vascular risk according to the Framingham risk score as well as a baseline and 5-year follow-up neurological examination. MPS were defined according to established criteria based on the entire motor section of the Unified PD Rating Scale. Participants with PD at baseline or follow-up and subjects with MPS at baseline were excluded. A logistic regression analysis adjusted for age and sex was used to detect risk factors for incident MPS in the remaining 393 participants. SN-hyperechogenicity and hyposmia were related to the development of MPS with odds ratios of 2.0 (95%CI, 1.1-3.7) and 1.6 (95%CI, 1.0-2.7), respectively, while increased vascular risk was not. Having both, SN-hyperechogenicity and hyposmia, was associated with an odds ratio of 3.0 (95%CI, 1.2-7.7) for incident MPS. Among the various motor domains, increased SN-echogenicity predicted the development of bradykinesia and rigidity, whereas diminished olfactory function predicted the development of impaired axial motor function. In addition to their established roles as risk factors for PD, SN-hyperechogenicity and hyposmia are associated with an increased risk for MPS in the general elderly community. Copyright © 2015 Elsevier Ltd. All rights reserved.
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    • "Although the effects of PD on basal ganglia functions have been extensively studied, much less is known about the functional consequences because of normal aging. As a result, the treatments for ageassociated motor dysfunctions are even more limited than for PD (Buchman et al., 2012). Differentiating idiopathic PD from atypical PD syndromes, especially in the early disease stages, has proven to be difficult because of an overlap of clinical signs and symptoms. "
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    • "Parkinson’s disease (PD) is a neurodegenerative illness whose onset and progression is clearly linked to aging (Driver et al., 2009; Buchman et al., 2012). The discovery of cell loss and eosiniphilic intracitoplasmic aggregates (Lewy bodies) in the substantia nigra (SN) of these patients during the early twentieth century (Greenfield and Bosanquet, 1953) led a number of groups to investigate the etio-pathology of PD in this center. "
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