scholarly journals Distinct patterns of speech disorder in early-onset and late-onset de-novo Parkinson’s disease

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jan Rusz ◽  
Tereza Tykalová ◽  
Michal Novotný ◽  
Evžen Růžička ◽  
Petr Dušek
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Standard Deviation ◽  
Early Onset ◽  
De Novo ◽  
Late Onset ◽  
Age At Onset ◽  
Distinct Pattern ◽  
Speech Disorder ◽  
Motor Symptom

AbstractSubstantial variability and severity of dysarthric patterns across Parkinson’s disease (PD) patients may reflect distinct phenotypic differences. We aimed to compare patterns of speech disorder in early-onset PD (EOPD) and late-onset PD (LOPD) in drug-naive patients at early stages of disease. Speech samples were acquired from a total of 96 participants, including two subgroups of 24 de-novo PD patients and two subgroups of 24 age- and sex-matched young and old healthy controls. The EOPD group included patients with age at onset below 51 (mean 42.6, standard deviation 6.1) years and LOPD group patients with age at onset above 69 (mean 73.9, standard deviation 3.0) years. Quantitative acoustic vocal assessment of 10 unique speech dimensions related to respiration, phonation, articulation, prosody, and speech timing was performed. Despite similar perceptual dysarthria severity in both PD subgroups, EOPD showed weaker inspirations (p = 0.03), while LOPD was characterized by decreased voice quality (p = 0.02) and imprecise consonant articulation (p = 0.03). In addition, age-independent occurrence of monopitch (p < 0.001), monoloudness (p = 0.008), and articulatory decay (p = 0.04) was observed in both PD subgroups. The worsening of consonant articulation was correlated with the severity of axial gait symptoms (r = 0.38, p = 0.008). Speech abnormalities in EOPD and LOPD share common features but also show phenotype-specific characteristics, likely reflecting the influence of aging on the process of neurodegeneration. The distinct pattern of imprecise consonant articulation can be interpreted as an axial motor symptom of PD.

The Evolution of Dementia in Idiopathic Parkinson's Disease: Neuropsychological and Clinical Evidence in Support of Subtypes

1992 ◽  
Vol 4 (4) ◽  
pp. 147-160 ◽  
Author(s):  
Wayne G. J. Reid
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Onset ◽  
Late Onset ◽  
Age At Onset ◽  
Critical Determinant ◽  
Drug Study ◽  
Baseline Phase ◽  
Onset Group ◽  
Early Onset Group

One hundred and seven newly diagnosed, untreated patients with Parkinson's disease (PD) were divided into two groups according to their age at reported onset of symptoms. Of these, 79 patients were under age 70 (early-onset) and 28 patients were age 70 and over (late-onset). The group of 50 control subjects comprised spouses, friends of the PD patients, and community volunteers. The patients were participants in a multicenter drug study of Parkinson's disease. Each had received a detailed neurological and neuropsychological assessment in the baseline placebo phases of the study. Thirty-4 patients with early-onset and 12 patients with late-onset were reassessed 3 years after treatment with low-dose levodopa, with bromocriptine, or with a combination of the two drugs. The results of the baseline phase of the study revealed that 8% of the early-onset group and 32% of the late-onset group were classified as demented. The 3-year follow-up revealed that the prevalence of dementia had increased to 17% in the early-onset group and to 83% in the late-onset group. This study confirms that at least two distinct subtypes of Parkinson's disease exist. The subtypes differ both clinically and neuropsychologically. The age at onset of symptoms is a critical determinant of the rate and type of cognitive decline in Parkinson's disease.

scholarly journals Gene4PD: A Comprehensive Genetic Database of Parkinson’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Bin Li ◽  
Guihu Zhao ◽  
Qiao Zhou ◽  
Yali Xie ◽  
Zheng Wang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Late Onset ◽  
Association Studies ◽  
Age At Onset ◽  
Genetic Data ◽  
Genome Wide Association Studies ◽  
Onset Age ◽  
Loss Of Function

Parkinson’s disease (PD) is a complex neurodegenerative disorder with a strong genetic component. A growing number of variants and genes have been reported to be associated with PD; however, there is no database that integrate different type of genetic data, and support analyzing of PD-associated genes (PAGs). By systematic review and curation of multiple lines of public studies, we integrate multiple layers of genetic data (rare variants and copy-number variants identified from patients with PD, associated variants identified from genome-wide association studies, differentially expressed genes, and differential DNA methylation genes) and age at onset in PD. We integrated five layers of genetic data (8302 terms) with different levels of evidences from more than 3,000 studies and prioritized 124 PAGs with strong or suggestive evidences. These PAGs were identified to be significantly interacted with each other and formed an interconnected functional network enriched in several functional pathways involved in PD, suggesting these genes may contribute to the pathogenesis of PD. Furthermore, we identified 10 genes were associated with a juvenile-onset (age ≤ 30 years), 11 genes were associated with an early-onset (age of 30–50 years), whereas another 10 genes were associated with a late-onset (age &gt; 50 years). Notably, the AAOs of patients with loss of function variants in five genes were significantly lower than that of patients with deleterious missense variants, while patients with VPS13C (P = 0.01) was opposite. Finally, we developed an online database named Gene4PD (http://genemed.tech/gene4pd) which integrated published genetic data in PD, the PAGs, and 63 popular genomic data sources, as well as an online pipeline for prioritize risk variants in PD. In conclusion, Gene4PD provides researchers and clinicians comprehensive genetic knowledge and analytic platform for PD, and would also improve the understanding of pathogenesis in PD.

scholarly journals FAKTOR-FAKTOR YANG MEMPENGARUHI SUBTIPE GEJALA MOTORIK PENYAKIT PARKINSON

2020 ◽  
Vol 5 (1) ◽  
pp. 343
Author(s):  
Attiya Istarini ◽  
Yuliarni Syafrita ◽  
Restu Susanti
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Age At Onset ◽  
Motor Symptom ◽  
Disease Stage ◽  
Motor Symptoms ◽  
Research Subjects ◽  
Cross Sectional ◽  
Duration Of Disease ◽  
Cross Sectional Design

<p><strong><em>Background</em></strong><em>: Parkinson's disease (PD) is a chronic neurodegenerative disease that manifests as movement disorders. Based on motor symptoms, PD is classified into subtypes of tremor and postural instability gait disorders (PIGD). The motor symptoms subtype is a predictor of disease progression, therapeutic response, and quality of life for Parkinson's patients. The purpose of this study is to identify some  factors that influence motor symptoms in Parkinson's disease.</em><strong><em>Methods:</em></strong><em> This research use cross sectional design. Samples were selected by consecutive sampling method that met the inclusion and exclusion criteria. Research subjects were 58 people. Statistical analysis using SPSS. p values &lt;0.05 were considered statistically significant.</em><strong><em>Results:</em></strong><em> This research include 58 patients, 55.2% were men with range of age 63.5 ± 8.5 years old. The mean age at onset was 57.9 ± 9.5 years and duration of disease 6.1 ± 4.6 years. Motor symptoms 53.4% dominant tremor. There was a significant relationship between disease stage and motor symptom subtypes (p &lt;0.001). There is no relationship between the patient's age, age at onset and duration of the disease with motor symptom subtypes.</em><strong><em>Conclusions:</em></strong><em> There is a relationship between disease stage and motor symptom. The patient's age, age at onset and duration of the disease are not related to the motor symptoms of Parkinson's patients.</em></p>

scholarly journals The Association Between Lysosomal Storage Disorder Genes and Parkinson’s Disease: A Large Cohort Study in Chinese Mainland Population

2021 ◽  
Vol 13 ◽  
Author(s):  
Yu-wen Zhao ◽  
Hong-xu Pan ◽  
Zhenhua Liu ◽  
Yige Wang ◽  
Qian Zeng ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Onset ◽  
Lysosomal Storage Disorder ◽  
Rare Variants ◽  
Late Onset ◽  
Chinese Mainland ◽  
Lysosomal Storage ◽  
Post Translational Modification ◽  
Storage Disorder

Background: Recent years have witnessed an increasing number of studies indicating an essential role of the lysosomal dysfunction in Parkinson’s disease (PD) at the genetic, biochemical, and cellular pathway levels. In this study, we investigated the association between rare variants in lysosomal storage disorder (LSD) genes and Chinese mainland PD.Methods: We explored the association between rare variants of 69 LSD genes and PD in 3,879 patients and 2,931 controls from Parkinson’s Disease &amp; Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC) using next-generation sequencing, which were analyzed by using the optimized sequence kernel association test.Results: We identified the significant burden of rare putative LSD gene variants in Chinese mainland patients with PD. This association was robust in familial or sporadic early-onset patients after excluding the GBA variants but not in sporadic late-onset patients. The burden analysis of variant sets in genes of LSD subgroups revealed a suggestive significant association between variant sets in genes of sphingolipidosis deficiency disorders and familial or sporadic early-onset patients. In contrast, variant sets in genes of sphingolipidoses, mucopolysaccharidoses, and post-translational modification defect disorders were suggestively associated with sporadic late-onset patients. Then, SMPD1 and other four novel genes (i.e., GUSB, CLN6, PPT1, and SCARB2) were suggestively associated with sporadic early-onset or familial patients, whereas GALNS and NAGA were suggestively associated with late-onset patients.Conclusion: Our findings supported the association between LSD genes and PD and revealed several novel risk genes in Chinese mainland patients with PD, which confirmed the importance of lysosomal mechanisms in PD pathogenesis. Moreover, we identified the genetic heterogeneity in early-onset and late-onset of patients with PD, which may provide valuable suggestions for the treatment.

scholarly journals Preserved Serotonergic Activity in Early-Onset Parkinson’s Disease

2019 ◽  
Vol 47 (3) ◽  
pp. 344-349 ◽  
Author(s):  
Hee Kyung Park ◽  
Jae-Jung Lee ◽  
Young-Min Park
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Onset ◽  
Auditory Evoked Potentials ◽  
Late Onset ◽  
Post Treatment ◽  
Dopaminergic Medication ◽  
Serotonergic Activity ◽  
The Absolute ◽  
Onset Group

ABSTRACT:Background:Serotonergic dysfunction may play an important role in motor and nonmotor symptoms of Parkinson’s disease (PD). The loudness dependence of auditory evoked potentials (LDAEP) has been used to evaluate serotonergic activity. Therefore, this study aimed to determine central serotonergic activity using LDAEP in de novo PD according to the age at onset and changes in serotonergic activity after dopaminergic treatment.Methods:A total of 30 patients with unmedicated PD, 16 in the early-onset and 14 in the late-onset groups, were enrolled. All subjects underwent comprehensive neurological examination, laboratory tests, the Unified Parkinson’s Disease Rating Scale, and LDAEP. The LDAEP was calculated as the slope of the two N1/P2 peaks measured at the Cz electrode, first at baseline conditions (pretreatment) and a second time after 12 weeks (post-treatment) following dopaminergic medications.Results:The absolute values of pretreatment N1/P2 LDAEP (early-onset: late-onset, 0.99 ± 0.68: 1.62 ± 0.88, p = 0.035) and post-treatment N1 LDAEP (early-onset: late-onset, −0.61 ± 0.61: −1.26 ± 0.91, p = 0.03) were significantly lower in the early-onset group compared with those of the late-onset group. In addition, a higher value of pretreatment N1/P2 LDAEP was significantly correlated with the late-onset group (coefficient = 1.204, p = 0.044). The absolute value of the N1 LDAEP decreased after 12 weeks of taking dopaminergic medication (pretreatment: post-treatment, −1.457 ± 1.078: −0.904 ± 0.812, p = 0.0018).Conclusions:Based on the results of this study, LDAEP could be a marker for serotonergic neurotransmission in PD. Central serotonergic activity assessed by LDAEP may be more preserved in early-onset PD patients and can be altered with dopaminergic medication.

scholarly journals Different Alterations of Cerebral Regional Homogeneity in Early-Onset and Late-Onset Parkinson's Disease

2016 ◽  
Vol 8 ◽  
Author(s):  
Ke Sheng ◽  
Weidong Fang ◽  
Yingcheng Zhu ◽  
Guangying Shuai ◽  
Dezhi Zou ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Onset ◽  
Late Onset ◽  
Regional Homogeneity

scholarly journals Whole-exome analysis in Parkinson’s disease reveals a high burden of ultra rare variants in early onset cases

2020 ◽  
Author(s):  
Bernabe I. Bustos ◽  
Dimitri Krainc ◽  
Steven J. Lubbe ◽  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Onset ◽  
Rare Variants ◽  
Neurodegenerative Disorder ◽  
Age Of Onset ◽  
Late Onset ◽  
Genetic Component ◽  
Genetic Risk Assessment ◽  
Whole Exome

ABSTRACTParkinson’s disease (PD) is a complex neurodegenerative disorder with a strong genetic component. We performed a “hypothesis-free” exome-wide burden-based analysis of different variant frequencies, predicted functional impact and age of onset classes, in order to expand the understanding of rare variants in PD. Analyzing whole-exome data from a total of 1,425 PD cases and 596 controls, we found a significantly increased burden of ultra-rare (URV= private variants absent from gnomAD) protein altering variants (PAV) in early-onset PD cases (EOPD, <40 years old; P=3.95×10−26, beta=0.16, SE=0.02), compared to LOPD cases (>60 years old, late-onset), where more common PAVs (allele frequencies <0.001) showed the highest significance and effect (P=0.026, beta=0.15, SE=0.07). Gene-set burden analysis of URVs in EOPD highlighted significant disease- and tissue-relevant genes, pathways and protein-protein interaction networks that were different to that observed in non-EOPD cases. Heritability estimates revealed that URVs account for 15.9% of the genetic component in EOPD individuals. Our results suggest that URVs play a significant role in EOPD and that distinct etiological bases may exist for EOPD and sporadic PD. By providing new insights into the genetic architecture of PD, our study may inform approaches aimed at novel gene discovery and provide new directions for genetic risk assessment based on disease age of onset.

scholarly journals Genetic analysis of Mendelian mutations in a large UK population-based Parkinson’s disease study

Brain ◽  
2019 ◽  
Vol 142 (9) ◽  
pp. 2828-2844 ◽  
Author(s):  
Manuela M X Tan ◽  
Naveed Malek ◽  
Michael A Lawton ◽  
Leon Hubbard ◽  
Alan M Pittman ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Exome Sequencing ◽  
Clinical Features ◽  
Late Onset ◽  
Age At Onset ◽  
Population Based ◽  
Data Movement ◽  
Young Onset ◽  
Number Of Patients

AbstractOur objective was to define the prevalence and clinical features of genetic Parkinson’s disease in a large UK population-based cohort, the largest multicentre prospective clinico-genetic incident study in the world. We collected demographic data, Movement Disorder Society Unified Parkinson’s Disease Rating Scale scores, and Montreal Cognitive Assessment scores. We analysed mutations in PRKN (parkin), PINK1, LRRK2 and SNCA in relation to age at symptom onset, family history and clinical features. Of the 2262 participants recruited to the Tracking Parkinson’s study, 424 had young-onset Parkinson’s disease (age at onset ≤ 50) and 1799 had late onset Parkinson’s disease. A range of methods were used to genotype 2005 patients: 302 young-onset patients were fully genotyped with multiplex ligation-dependent probe amplification and either Sanger and/or exome sequencing; and 1701 late-onset patients were genotyped with the LRRK2 ‘Kompetitive’ allele-specific polymerase chain reaction assay and/or exome sequencing (two patients had missing age at onset). We identified 29 (1.4%) patients carrying pathogenic mutations. Eighteen patients carried the G2019S or R1441C mutations in LRRK2, and one patient carried a heterozygous duplication in SNCA. In PRKN, we identified patients carrying deletions of exons 1, 4 and 5, and P113Xfs, R275W, G430D and R33X. In PINK1, two patients carried deletions in exon 1 and 5, and the W90Xfs point mutation. Eighteen per cent of patients with age at onset ≤30 and 7.4% of patients from large dominant families carried pathogenic Mendelian gene mutations. Of all young-onset patients, 10 (3.3%) carried biallelic mutations in PRKN or PINK1. Across the whole cohort, 18 patients (0.9%) carried pathogenic LRRK2 mutations and one (0.05%) carried an SNCA duplication. There is a significant burden of LRRK2 G2019S in patients with both apparently sporadic and familial disease. In young-onset patients, dominant and recessive mutations were equally common. There were no differences in clinical features between LRRK2 carriers and non-carriers. However, we did find that PRKN and PINK1 mutation carriers have distinctive clinical features compared to young-onset non-carriers, with more postural symptoms at diagnosis and less cognitive impairment, after adjusting for age and disease duration. This supports the idea that there is a distinct clinical profile of PRKN and PINK1-related Parkinson’s disease. We estimate that there are approaching 1000 patients with a known genetic aetiology in the UK Parkinson’s disease population. A small but significant number of patients carry causal variants in LRRK2, SNCA, PRKN and PINK1 that could potentially be targeted by new therapies, such as LRRK2 inhibitors.

scholarly journals Early-onset Parkinson's disease and depression

2007 ◽  
Vol 65 (1) ◽  
pp. 5-10 ◽  
Author(s):  
Délcio Bertucci Filho ◽  
Hélio A.G. Teive ◽  
Lineu C. Werneck
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Risk Factor ◽  
Parkinson Disease ◽  
Early Onset ◽  
Clinical Characteristics ◽  
Late Onset ◽  
Mild Depression ◽  
Moderate Depression ◽  
Early Onset Parkinson’S Disease

Patients with Parkinson’s disease (PD) in whom symptoms start before the age of 45 years (EOPD) present different clinical characteristics from those with the late-onset form of the disease. The incidence of depression is believed to be greater in patients with EOPD than with the late-onset form of the disease, although there is no risk factor or marker for depression in patients with PD. We studied 45 patients with EOPD to define the frequency of depression and to identify possible differences between the groups with and without depression. Depression was diagnosed in 16 (35.5%) of the patients, a higher incidence than in the population at large but similar to the figure for late-onset Parkinson disease; 8 (50%) of the patients had mild depression, 4 (25%) moderate depression and 4 (25%) were in remission. There was no relationship between depression and any of the clinical characteristics of the disease, although the EOPD patients with depression presented earlier levodopa-related complications and were more affected on the Hoehn-Yahr, UPDRS and Schwab-England scales.

Genetic Insights into Early-onset Parkinson’s Disease

US Neurology ◽  
2010 ◽  
Vol 06 (01) ◽  
pp. 41
Author(s):  
Roy N Alcalay ◽  
Cheryl Waters ◽  
◽  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Family History ◽  
Early Onset ◽  
Late Onset ◽  
Positive Family History ◽  
Disease Onset ◽  
Leucine Rich Repeat ◽  
Strong Family History ◽  
Early Onset Parkinson’S Disease

Early-onset Parkinson’s disease (EOPD) is defined as disease onset before 40 or 50 years of age. The clinical characteristics of EOPD are very similar to those of late-onset PD, but dystonia is more often a presenting symptom, dementia is rare, and disease progression may be slower. Mutations in several genes have been described in cases with EOPD, often with strong family history, including mutations in α-synuclein (SNCA),DJ-1, PTEN-induced kinase-1 (PINK-1), andATP13A2. However, the most common mutations identified in EOPD are in Parkin (PRKN), leucine-rich repeat kinase 2 (LRRK2), and glucocerebrosidase (GBA). With the exception ofSNCAandATP13A2carriers, mutation carriers are often indistinguishable from non-carriers. Large series of EOPD cases that are not ascertained by family history estimate mutation frequency at 4–16%. Given that the frequency of positive family history is much higher, we believe that many genetic risk factors are yet to be discovered.

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