Functional significance of age-associated nigostriatal dopaminergic denervation in healthy subjects

Abstract

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Objectives: To investigate the functional significance of age-associated nigrostriatal dopaminergic denervation in community-dwelling healthy subjects.

Methods: Community-dwelling normal subjects (n=49, 27 females and 22 males, mean age 53.0±14.1, range 20-84 years) underwent clinical examination and C-11-beta-CFT dopamine transporter (DAT) PET imaging. The grooved pegboard test was selected as a quantitative test of upper limb bradykinesia. The Berg scale was used for assessment of balance, the University of Pennsylvania Smell Identification Test (UPSIT) was used for quantitative assessment of olfaction. Cognitive tests included the Mini-Mental State Examination (MMSE) and the Stroop Color-Word Interference Test. Rating scales of depression and anxiety were also administered. Subjects who had evidence of Parkinson’s disease on clinical examination were excluded from the study. PET imaging was performed using a Siemens HR+ PET scanner in 3D mode. Striatal region of interest were drawn on MR images and transferred to the registered PET scans.

Results: There was a significant effect of age on striatal DAT activity (P<0.0001). Coefficients of correlations between the striatal DAT binding potential and the clinical measures are listed in the table. [table]

Conclusions: Age-associated nigrostriatal dopaminergic denervation is associated with functional impairments of bradykinesia, balance, smell and executive cognitive functions. These results run counter to the dogma derived largely from the literature on Parkinson’s disease (PD), in which it has been suggested that an 80% or greater loss of nigrostriatal dopamine function has to occur before clinical manifestations of functional impairment would be evident. The fact that this association is observed in normal subjects indicates that while no symptoms of PD are present, the decline in brain dopamine activity may lead to a decline in the individual's general motor, cognitive executive and olfactory functions.

Research Support (if any): Supported by Department of Veterans Affairs and NS019608.