Age-specific progression of nigrostriatal dysfunction in Parkinson's disease

Raúl De La Fuente-Fernández, Michael Schulzer, Lisa Kuramoto, Jacquelyn Cragg, Nandhagopal Ramachandiran, Wing L. Au, Edwin Mak, Jess McKenzie, Siobhan McCormick, Vesna Sossi, Thomas J. Ruth, Chong S. Lee, Donald B. Calne, A. Jon Stoessl

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Abstract

Objective: To investigate in vivo the impact of age on nigrostriatal dopamine dysfunction in Parkinson's disease (PD). Methods: PD patients (n = 78) and healthy control subjects (n = 35) underwent longitudinal positron emission tomography assessments using 3 presynaptic dopamine markers: (1) [ 11C](±)dihydrotetrabenazine (DTBZ), to estimate the density of the vesicular monoamine transporter type 2; (2) [11C]d-threo- methylphenidate, to estimate the density of the plasma membrane dopamine transporter; and (3) 6-[18F]-fluoro-L-dopa, to estimate the activity of the enzyme dopa-decarboxylase. Results: The study comprised 438 PD scans and 241 control scans (679 scans in total). At symptom onset, the loss of putamen DTBZ binding was substantially greater in younger compared to older PD patients (p = 0.015). Remarkably, however, the rate of progression of DTBZ binding loss was significantly slower in younger patients (p <0.05). The estimated presymptomatic phase of the disease spanned more than 2 decades in younger patients, compared to 1 decade in older patients. Interpretation: Our results suggest that, compared to older patients, younger PD patients progress more slowly and are able to endure more damage to the dopaminergic system before the first motor symptoms appear. These observations suggest that younger PD patients have more efficient compensatory mechanisms.

Original languageEnglish
Pages (from-to)803-810
Number of pages8
JournalAnnals of Neurology
Volume69
Issue number5
DOIs
Publication statusPublished - May 2011

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ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

De La Fuente-Fernández, R., Schulzer, M., Kuramoto, L., Cragg, J., Ramachandiran, N., Au, W. L., Mak, E., McKenzie, J., McCormick, S., Sossi, V., Ruth, T. J., Lee, C. S., Calne, D. B., & Stoessl, A. J. (2011). Age-specific progression of nigrostriatal dysfunction in Parkinson's disease. Annals of Neurology, 69(5), 803-810. https://doi.org/10.1002/ana.22284