Age at onset and Parkinson disease phenotype
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Published version
Author(s)
Pagano, G
Ferrara, N
Brooks, DJ
Pavese, N
Type
Journal Article
Abstract
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 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.
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.
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 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.
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.
Date Issued
2016-02-10
Date Acceptance
2016-02-01
Citation
Neurology, 2016, 86 (15), pp.1400-1407
ISSN
0028-3878
Publisher
American Academy of Neurology
Start Page
1400
End Page
1407
Journal / Book Title
Neurology
Volume
86
Issue
15
Sponsor
Michael J Fox Foundation
Grant Number
PPMI/5583709074FF
Subjects
Science & Technology
Life Sciences & Biomedicine
Clinical Neurology
Neurosciences & Neurology
CLINICAL-FEATURES
YOUNG-ONSET
METAANALYSIS
PROGRESSION
HETEROGENEITY
PREVALENCE
MOTOR
Age of Onset
Aged
Amyloid beta-Peptides
Biomarkers
Caudate Nucleus
Databases, Factual
Female
Functional Laterality
Humans
Male
Middle Aged
Parkinson Disease
Peptide Fragments
Phenotype
Phosphorylation
Putamen
Severity of Illness Index
Tomography, Emission-Computed, Single-Photon
Uric Acid
alpha-Synuclein
tau Proteins
Neurology & Neurosurgery
1103 Clinical Sciences
1109 Neurosciences
1702 Cognitive Science
Publication Status
Published