Age at onset and Parkinson disease phenotype

TLDR

The study investigates the clinical phenotype and characteristics of Parkinson disease at different ages at onset in newly diagnosed, untreated patients using baseline data from the Parkinson's Progression Markers Initiative. Researchers divided 422 DaTSCAN‑confirmed PD patients into four age‑onset groups and examined differences in symptom side, type, localization, motor and non‑motor severity, nigrostriatal function, and CSF biomarkers. Patients with PD present similarly across age groups, most commonly with bradykinesia, resting tremor, and rigidity (rigidity more frequent in younger onset), but older onset is linked to greater motor/non‑motor severity, worse DaTSCAN binding, lower CSF α‑synuclein and total tau, and greater biomarker variability that may challenge future clinical trials.

Abstract

To explore clinical phenotype and characteristics of Parkinson disease (PD) at different ages at onset in recently diagnosed patients with untreated PD.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.Older age at onset was associated with a more severe motor and nonmotor phenotype, a greater dopaminergic dysfunction on DaTSCAN, and reduction of CSF α-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.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.