Onset Age-related Subtypes Of Parkinson’s Disease Differ In The Patterns Of Striatal Dopaminergic Disruption:A PET Study

Parkinson’s disease is highly clinically heterogeneous that a number of studies have proposed and defined subtypes of Parkinson’s disease on the basis of clinical or demographic features. Based on the onset of the disease, Parkinson’s disease can be classified into two groups:young-onset Parkinson’s disease that occurs on or before 50 years of age but later than 20 years of age and late-onset Parkinson’s disease that begins after 50 years of age. Young-onset subtype differs with the late-onset subtype in drug responsiveness, incidence of motor complications and prognosis, representing a key challenge in understanding the underlying pathophysiology and etiology.Objective To evaluate the impact of age of onset on the pattern of dopaminergic disruption of striatum (caudate and putamen) in Parkinson’s disease patients and to further investigate the relationship between the patterns and clinical features of the onset age-related subtypes from an anatomical and pathophysiological perspective.Methods We assessed the spatial pattern of striatal dopaminergic disruption in 40 young-onset and 47 late-onset patients with early to mid-stage Parkinson’s disease with 2β-carbomethoxy-3β-(4-fluorophenyl)-(N-11C-methyl) tropane positron emission tomography ([11C]-CFT PET) scans. Patients with Parkinson’s disease were recruited from movement disorder clinics of Huashan Hospital. All of them fulfilled the UK PD Brain Bank Criteria. On the day of [11C]-CFT PET scan, patients underwent a full neurological examination including disease duration, Hoehn and Yahr score and Unified Parkinson’s disease Rating Scale (UPDRS Ⅲ) off medication for at least 12 hours. We estimated caudate and putamen dopamine transporter binding (DAT binding) separately for each hemisphere by the striatal-to-occipital ratio (SOR), and measured the spatial pattern of striatal dopaminergic disruption by two sub-regional parameters (caudate/putamen ratios and asymmetry index).ResultsWe found evidences for uneven pattern of more impairment in the function of the presynaptic dopaminergic system in putamen and relative sparing of the caudate in the young-onset subtype of Parkinson’s disease with a relative uniform pattern in the late-onset group. The caudate/anterior putamen ratios were significantly higher in young-onset patients than that observed in the late-onset group at both contralateral and ipsilateral sides (p= 0.03 contralateral; p= 0.004 ipsilateral), supported by significantly inverse correlations between age of onset and caudate/anterior putamen ratios (r=— 0.428, p<0.001 and r=—0.576, p<0.001). Regional disruption of striatal dopaminergic system of caudate on ipsilateral side was significantly correlated with age or age of onset, while putamen but not caudate dopamine transporter binding values were significantly inversely correlated with disease duration or Unified Parkinson’s Disease Rating Scale motor scores.ConclusionYoung-onset and late-onset Parkinson’s disease subtypes differ in underlying patterns of dopaminergic disruption. The onset age-related patterns of striatal dopaminergic disruption are consistent with motor and neuropsychological features of these two subtypes explained by neuroanatomy theory and neuropathology in Parkinson’s disease. The differences between subtypes may result from co-effect of aging and other individual specific factors. The knowledge of Parkinson’s disease subtypes can be used in future research of this disease and in improvement of individually specific therapies and patient management.