Onset-related subtypes of Parkinson's disease differ in the patterns of striatal dopaminergic dysfunction: A positron emission tomography study

Parkinsonism Relat Disord. 2015 Dec;21(12):1448-53. doi: 10.1016/j.parkreldis.2015.10.017. Epub 2015 Oct 30.

Abstract

Purpose: The young-onset subtype of Parkinson's disease (YOPD) differs from the late-onset subtype (LOPD) in drug responsiveness, incidence of motor complications, and prognosis. The pathophysiology underlying these differences remains largely unknown. This study investigated whether the two subtypes differ in the pattern of dysfunction in striatal (caudate and putamen) dopaminergic system and if the dopamine transporter (DAT) imaging patterns are associated with the clinical features of corresponding PD subtype.

Methods: We assessed the spatial pattern of striatal dopaminergic dysfunction in 40 YOPD and 47 LOPD with early to mid-stage PD with DAT imaging by positron emission tomography. Two sub-regional parameters (caudate/putamen ratio and asymmetry index) were calculated to measure the spatial pattern of striatal dopaminergic dysfunction.

Results: The caudate/anterior putamen ratios were significantly higher in YOPD than that in the LOPD (P = 0.03 contralateral to the most affected side of the body and P = 0.004 ipsilateral), which was supported by significantly inverse correlations between age of onset and caudate/anterior putamen ratios (r = -0.428, P < 0.001 for the contralateral and r = -0.576, P < 0.001 for the ipsilateral). Sub-regional DAT binding in caudate ipsilateral to affected limbs was significantly correlated with age, while DAT bindings in putamen were significantly inversely correlated with disease duration and UPDRS motor scores.

Conclusion: The YOPD subtype suffers from an uneven pattern of dopaminergic dysfunction: more sparing of the caudate compared with the putamen, while the LOPD patients is with a relatively uniform pattern.

Keywords: Age of onset; Parkinson's disease; Subtype; [(11)C]-CFT PET.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Carbon Radioisotopes / analysis
  • Carbon Radioisotopes / pharmacokinetics
  • Caudate Nucleus / chemistry
  • Caudate Nucleus / diagnostic imaging*
  • Caudate Nucleus / pathology
  • Cocaine / analogs & derivatives
  • Cocaine / analysis
  • Cocaine / pharmacokinetics
  • Dopamine Plasma Membrane Transport Proteins / analysis*
  • Dopaminergic Neurons / chemistry
  • Dopaminergic Neurons / diagnostic imaging*
  • Dopaminergic Neurons / pathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neuroimaging / methods*
  • Organ Specificity
  • Parkinson Disease / classification
  • Parkinson Disease / diagnostic imaging*
  • Parkinson Disease / pathology
  • Parkinson Disease / physiopathology
  • Positron-Emission Tomography*
  • Putamen / chemistry
  • Putamen / diagnostic imaging*
  • Putamen / pathology
  • Radiopharmaceuticals / analysis
  • Radiopharmaceuticals / pharmacokinetics
  • Tissue Distribution

Substances

  • Carbon Radioisotopes
  • Dopamine Plasma Membrane Transport Proteins
  • Radiopharmaceuticals
  • (1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester
  • Cocaine