Original Article

Nigral pathology and parkinsonian signs in elders without Parkinson disease

  1. Aron S. Buchman MD1,2,*,
  2. Joshua M. Shulman MD, PhD3,4,
  3. Sukriti Nag MD, PhD1,5,
  4. Sue E. Leurgans PhD1,2,
  5. Steven E. Arnold MD5,
  6. Martha C. Morris ScD6,
  7. Julie A. Schneider MD, MS1,2,7,
  8. David A. Bennett MD1,2

Article first published online: 24 FEB 2012

DOI: 10.1002/ana.22588

Issue

Annals of Neurology

Annals of Neurology

Volume 71, Issue 2, pages 258–266, February 2012

Additional Information

How to Cite

Buchman, A. S., Shulman, J. M., Nag, S., Leurgans, S. E., Arnold, S. E., Morris, M. C., Schneider, J. A. and Bennett, D. A. (2012), Nigral pathology and parkinsonian signs in elders without Parkinson disease. Ann Neurol., 71: 258–266. doi: 10.1002/ana.22588

Author Information

  1. 1

    Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL

  2. 2

    Department of Neurological Sciences, Rush University Medical Center, Chicago, IL

  3. 3

    Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts

  4. 4

    Department of Neurology, Harvard Medical School, Boston, Massachusetts

  5. 5

    Departments of Psychiatry and Neurology, Center for Neurobiology and Behavior, University of Pennsylvania, Philadelphia, PA

  6. 6

    Departments of Internal Medicine, Rush University Medical Center, Chicago, IL

  7. 7

    Departments of Pathology (Neuropathology), 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 60612

Publication History

  1. Issue published online: 24 FEB 2012
  2. Article first published online: 24 FEB 2012
  3. Accepted manuscript online: 11 AUG 2011 09:27AM EST
  4. Manuscript Accepted: 1 AUG 2011
  5. Manuscript Revised: 11 JUL 2011
  6. Manuscript Received: 28 FEB 2011

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Abstract

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

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