The motor phenotype of Parkinson's disease in relation to age at onset

Wickremaratchi, Mirdhu; Knipe, Duleeka; Sastry, B. S. D.; Morgan, Elizabeth A.; Jones, A; Salmon, Rachel; Weiser, Richard; Moran, Maralyn; Davies, Debbie; Ebenezer, Louise; Raha, Sandip; Robertson, Neil; Butler, Christopher Collett; Ben-Shlomo, Yoav; Morris, Huw R.

doi:10.1002/mds.23469

Cited by 133 publications

(103 citation statements)

References 21 publications

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“…32,34 The LIDs and non-LIDs groups of our PD cohort were clinically different (so that reached statistical significance) for sex, age, disease duration, the duration on dopaminergic medication, and LED Total . We performed separate analysis corrected for sex and found similar but less significant results compared to our whole cohort (male and female).…”

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confidence: 85%

“…Previous studies looking for clinical risk factors in LIDs have shown that the occurrence of LIDs is linked with younger age at onset of PD, [31][32][33] as well as with longer disease duration. 32,34 The LIDs and non-LIDs groups of our PD cohort were clinically different (so that reached statistical significance) for sex, age, disease duration, the duration on dopaminergic medication, and LED Total .…”

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confidence: 99%

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Serotonin-to-dopamine transporter ratios in Parkinson disease

et al. 2016

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Objective: To investigate whether a serotonin-to-dopamine terminal ratio is related to the appearance of dyskinesias in patients with Parkinson disease (PD).Methods: Twenty-eight patients with idiopathic PD (17 with levodopa-induced dyskinesias [LIDs], 11 without dyskinesias) and 12 age-matched healthy controls were studied with PET and 5[11 C]-3-amino-4-(2-dimethylaminomethylphenyl-sulfanyl)-benzonitrile ( 11 C-DASB) and with SPECT and [ 123 I]N-w-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl)nortropane ( 123 I-ioflupane), which are in vivo specific markers of the serotonin and dopamine transporters' availability, respectively. We have employed a simplified reference tissue model for the quantification of 11 C-DASB, whereas a semiquantification approach was used for 123 I-ioflupane data. We calculated 11 C-DASB binding to 123 I-ioflupane uptake ratios for the caudate and the putamen.Results: Patients with PD showed striatal decreases in 11 C-DASB binding potential (p , 0.01) and in 123 I-ioflupane mean uptake (p , 0.001) compared to controls. The mean 11 C-DASB binding to 123 I-ioflupane uptake ratio in the putamen was 0.779 (increased by 75.8% of the controls' mean) for the nondyskinetic group and 0.901 (increased by 103.4% of the controls' mean) for the patients with dyskinesias. There was a statistically significant difference (p , 0.001) in 11 C-DASB binding to 123 I-ioflupane uptake ratio in the putamen between the group of patients with and without dyskinesias. Higher 11 C-DASB to 123 I-ioflupane binding ratios correlated with longer disease duration for the 28 patients with PD (r 5 0.52; p , 0.01).Conclusions: Serotonin-to-dopamine transporter binding ratio increases as PD progresses and patients experience LIDs. Our findings suggest that, when the dopaminergic innervation in the striatum is critically low, the serotonergic system plays an important role in development of LIDs. Studies in the animal model of Parkinson disease (PD)1 as well as in humans 2-4 have indicated that degeneration of dopaminergic presynaptic terminals in the striatum is critical in the development of L-dopa-induced dyskinesias (LIDs). Due to the progressive degeneration, striatal dopaminergic terminals lose their dopamine storage capacity and the ability to maintain a stable dopamine release rate in the synapse. 5 Serotonergic terminals have been found capable of converting exogenous levodopa into dopamine, store it in synaptic vesicles, and release it in an activity-dependent manner. [6][7][8][9] The above studies propose that serotonergic terminals in the degenerating striatum are responsible for mishandling exogenous levodopa and exacerbating dyskinesia in the animal model 10-12 and PD.13 Accordingly, the presence of dyskinesia could be a reflection of serotonergic over

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Serotonin-to-dopamine transporter ratios in Parkinson disease

et al. 2016

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“…9 However, evidence supporting an influence of age on PD phenotype at its onset is lacking and conflicting. [10][11][12][13][14][15][16][17][18] Previous studies have poorly assessed the full spectrum of motor and nonmotor symptoms and they have not evaluated the relationship between PD phenotype and imaging and nonimaging biomarkers. The Parkinson's Progression Markers Initiative (PPMI) is an ongoing, international, multicenter, prospective study designed to discover and validate biomarkers of disease progression in newly diagnosed, drug-naive patients with PD.…”

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confidence: 99%

Age at onset and Parkinson disease phenotype

et al. 2016

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Objective: To explore clinical phenotype and characteristics of Parkinson disease (PD) at different ages at onset in recently diagnosed patients with untreated PD. Methods:We have analyzed baseline data from the Parkinson's Progression Markers Initiative database. Four hundred twenty-two patients with a diagnosis of PD confirmed by DaTSCAN imaging were divided into 4 groups according to age at onset (onset younger than 50 years, 50-59 years, 60-69 years, and 70 years or older) and investigated for differences in side, type and localization of symptoms, occurrence/severity of motor and nonmotor features, nigrostriatal function, and CSF biomarkers.Results: Older age at onset was associated with a more severe motor and nonmotor phenotype, a greater dopaminergic dysfunction on DaTSCAN, and reduction of CSF a-synuclein and total tau. The most common presentation was the combination of 2 or 3 motor symptoms (bradykinesia, resting tremor, and rigidity) with rigidity being more common in the young-onset group. In about 80% of the patients with localized onset, the arm was the most affected part of the body, with no difference across subgroups. Conclusions:Although the presentation of PD symptoms is similar across age subgroups, the severity of motor and nonmotor features, the impairment of striatal binding, and the levels of CSF biomarkers increase with age at onset. The variability of imaging and nonimaging biomarkers in patients with PD at different ages could hamper the results of future clinical trials.

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“…Parkinson disease (PD) is a degenerative and progressive disorder that mainly affects older people [1]. The rapid population ageing throughout developed countries means that the number of people diagnosed with PD will increase to over 10 million by 2050 [2].…”

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confidence: 99%