Nigral pathology and parkinsonian signs in elders without Parkinson disease
Corresponding Author
Aron S. Buchman MD
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL
Department of Neurological Sciences, Rush University Medical Center, Chicago, IL
Rush Alzheimer's Disease Center, Rush University Medical Center, Armour Academic Facility, Suite #1038, 600 South Paulina Street, Chicago, IL 60612Search for more papers by this authorJoshua M. Shulman MD, PhD
Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts
Department of Neurology, Harvard Medical School, Boston, Massachusetts
Search for more papers by this authorSukriti Nag MD, PhD
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL
Departments of Psychiatry and Neurology, Center for Neurobiology and Behavior, University of Pennsylvania, Philadelphia, PA
Search for more papers by this authorSue E. Leurgans PhD
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL
Department of Neurological Sciences, Rush University Medical Center, Chicago, IL
Search for more papers by this authorSteven E. Arnold MD
Departments of Psychiatry and Neurology, Center for Neurobiology and Behavior, University of Pennsylvania, Philadelphia, PA
Search for more papers by this authorMartha C. Morris ScD
Departments of Internal Medicine, Rush University Medical Center, Chicago, IL
Search for more papers by this authorJulie A. Schneider MD, MS
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL
Department of Neurological Sciences, Rush University Medical Center, Chicago, IL
Departments of Pathology (Neuropathology), Rush University Medical Center, Chicago, IL
Search for more papers by this authorDavid A. Bennett MD
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL
Department of Neurological Sciences, Rush University Medical Center, Chicago, IL
Search for more papers by this authorCorresponding Author
Aron S. Buchman MD
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL
Department of Neurological Sciences, Rush University Medical Center, Chicago, IL
Rush Alzheimer's Disease Center, Rush University Medical Center, Armour Academic Facility, Suite #1038, 600 South Paulina Street, Chicago, IL 60612Search for more papers by this authorJoshua M. Shulman MD, PhD
Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts
Department of Neurology, Harvard Medical School, Boston, Massachusetts
Search for more papers by this authorSukriti Nag MD, PhD
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL
Departments of Psychiatry and Neurology, Center for Neurobiology and Behavior, University of Pennsylvania, Philadelphia, PA
Search for more papers by this authorSue E. Leurgans PhD
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL
Department of Neurological Sciences, Rush University Medical Center, Chicago, IL
Search for more papers by this authorSteven E. Arnold MD
Departments of Psychiatry and Neurology, Center for Neurobiology and Behavior, University of Pennsylvania, Philadelphia, PA
Search for more papers by this authorMartha C. Morris ScD
Departments of Internal Medicine, Rush University Medical Center, Chicago, IL
Search for more papers by this authorJulie A. Schneider MD, MS
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL
Department of Neurological Sciences, Rush University Medical Center, Chicago, IL
Departments of Pathology (Neuropathology), Rush University Medical Center, Chicago, IL
Search for more papers by this authorDavid A. Bennett MD
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL
Department of Neurological Sciences, Rush University Medical Center, Chicago, IL
Search for more papers by this authorAbstract
Objective:
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).
Methods:
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.
Results:
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.
Interpretation:
Nigral pathology is common in persons without PD and may contribute to loss of motor function in old age. Ann Neurol 2012;71:258–266
Supporting Information
Additional supporting information can be found in the online version of this article.
| Filename | Description |
|---|---|
| ANA_22588_sm_SuppInfo.doc47.5 KB | Supporting Information |
| ANA_22588_sm_SuppTab1.doc65.5 KB | Supplementary Table 1. Raw mUPDRS Scores at the Last Visit Proximate to Death. |
| ANA_22588_sm_SuppTab2.doc71 KB | Supplementary Table 2. Distribution mUPDRS Item Scores for each of the 4 Groups of Nigral Pathology. |
| ANA_22588_sm_SuppTab3.doc56 KB | Supplemental Table 3. The Pattern of Nigral Neuronal Density in Older Persons Without PD. |
| ANA_22588_sm_SuppTab4.doc46 KB | Supplementary Table 4. Relation of Nigral Pathology and Global Parkinsonism: Sensitivity Analyses. |
| ANA_22588_sm_SuppTab5.doc39 KB | Supplemental Table 5. Correlation of Neuron Density in Other CNS Regions with Nigral Neuronal Loss and Global Parkinsonism. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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