Stochastic Epigenetic Mutations Influence Parkinson’s Disease Risk, Progression, and Mortality

2021 ◽  
pp. 1-12
Author(s):  
Gary K. Chen ◽  
Qi Yan ◽  
Kimberly C. Paul ◽  
Cynthia D.J. Kusters ◽  
Aline Duarte Folle ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Proportional Hazards ◽  
Disease Risk ◽  
Cox Proportional Hazards ◽  
Motor Symptom ◽  
Time To Death ◽  
Normal Site ◽  
Minimum Score ◽  
Symptom Progression

Background: Stochastic epigenetic mutations (SEM) reflect a deviation from normal site-specific methylation patterns. Epigenetic mutation load (EML) captures the accumulation of SEMs across an individual’s genome and may reflect dysfunction of the epigenetic maintenance system in response to epigenetic challenges. Objective: We investigate whether EML is associated with PD risk and time to events (i.e., death and motor symptom decline). Methods: We employed logistic regression and Cox proportional hazards regression to assess the association between EML and several outcomes. Our analyses are based on 568 PD patients and 238 controls from the Parkinson’s disease, Environment and Genes (PEG) study, for whom blood-based methylation data was available. Results: We found an association for PD onset and EML in all genes (OR = 1.90; 95%CI 1.52-2.37) and PD-related genes (OR = 1.87; 95%CI 1.50-2.32). EML was also associated with time to a minimum score of 35 points on the motor UPDRS exam (OR = 1.28; 95%CI 1.06-1.56) and time to death (OR = 1.29, 95%CI 1.11-1.49). An analysis of PD related genes only revealed five intragenic hotspots of high SEM density associated with PD risk. Conclusion: Our findings suggest an enrichment of methylation dysregulation in PD patients in general and specifically in five PD related genes. EML may also be associated with time to death and motor symptom progression in PD patients.

scholarly journals Parkinson’s Disease Motor Symptom Progression Slowed with Multisensory Dance Learning over 3-Years: A Preliminary Longitudinal Investigation

2021 ◽  
Vol 11 (7) ◽  
pp. 895
Author(s):  
Karolina A. Bearss ◽  
Joseph F. X. DeSouza
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Daily Living ◽  
Rating Scale ◽  
Motor Impairment ◽  
Motor Dysfunction ◽  
Motor Symptom ◽  
Significant Group ◽  
Rate Of Decline ◽  
Symptom Progression

Parkinson’s disease (PD) is a neurodegenerative disease that has a fast progression of motor dysfunction within the first 5 years of diagnosis, showing an annual motor rate of decline of the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) between 5.2 and 8.9 points. We aimed to determine both motor and non-motor PD symptom progression while participating in dance classes once per week over a period of three years. Longitudinal data was assessed for a total of 32 people with PD using MDS-UPDRS scores. Daily motor rate of decline was zero (slope = 0.000146) in PD-Dancers, indicating no motor impairment, whereas the PD-Reference group showed the expected motor decline across three years (p < 0.01). Similarly, non-motor aspects of daily living, motor experiences of daily living, and motor complications showed no significant decline. A significant group (PD-Dancers and PD-Reference) by days interaction showed that PD who train once per week have less motor impairment (M = 18.75) than PD-References who do not train (M = 24.61) over time (p < 0.05). Training is effective at slowing both motor and non-motor PD symptoms over three years as shown in decreased scores of the MDS-UPDRS.

scholarly journals Associations between concussion and risk of diagnosis of psychological and neurological disorders: a retrospective population-based cohort study

2020 ◽  
Vol 8 (3) ◽  
pp. e000390
Author(s):  
Marc P Morissette ◽  
Heather J Prior ◽  
Robert B Tate ◽  
John Wade ◽  
Jeff R S Leiter
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cohort Study ◽  
Proportional Hazards ◽  
Geographical Location ◽  
International Classification Of Diseases ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Control Group ◽  
Increased Risk

ObjectiveTo investigate associations between concussion and the risk of follow-up diagnoses of attention-deficit hyperactivity disorder (ADHD), mood and anxiety disorders (MADs), dementia and Parkinson’s disease.DesignA retrospective population-based cohort study.SettingAdministrative health data for the Province of Manitoba between 1990–1991 and 2014–2015.ParticipantsA total of 47 483 individuals were diagnosed with a concussion using International Classification of Diseases (ICD) codes (ICD-9-CM: 850; ICD-10-CA: S06.0). All concussed subjects were matched with healthy controls at a 3:1 ratio based on age, sex and geographical location. Associations between concussion and conditions of interest diagnosed later in life were assessed using a stratified Cox proportional hazards regression model, with adjustments for socioeconomic status and pre-existing medical conditions.Results28 021 men (mean age ±SD, 25±18 years) and 19 462 women (30±21 years) were included in the concussion group, while 81 871 men (25±18 years) and 57 159 women (30±21 years) were included in the matched control group. Concussion was associated with adjusted hazard ratios of 1.39 (95% CI 1.32 to 1.46, p<0.001) for ADHD, 1.72 (95% CI 1.69 to 1.76; p<0.001) for MADs, 1.72 (95% CI 1.61 to 1.84; p<0.001) for dementia and 1.57 (95% CI 1.41 to 1.75; p<0.001) for Parkinson’s disease.ConclusionConcussion was associated with an increased risk of diagnosis for all four conditions of interest later in life.

scholarly journals Focus on Depression in Parkinson’s Disease: A Delphi Consensus of Experts in Psychiatry, Neurology, and Geriatrics

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Luis Agüera-Ortiz ◽  
Rocío García-Ramos ◽  
Francisco J. Grandas Pérez ◽  
Jorge López-Álvarez ◽  
José Manuel Montes Rodríguez ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Disease Risk ◽  
Geriatric Depression Scale ◽  
Depression Scale ◽  
Motor Symptom ◽  
Mild Depression ◽  
Delphi Consensus ◽  
Serotonergic Drugs

Major and minor forms of depression are significant contributors to Parkinson’s disease morbidity and caregiver burden, affecting up to 50% of these patients. Nonetheless, symptoms of depression are still underrecognized and undertreated in this context due to scarcity of evidence and, consequently, consistent clinical guideline recommendations. Here, we carried out a prospective, multicentre, 2-round modified Delphi survey with 49 questions about the aetiopathological mechanisms of depression in Parkinson’s disease (10), clinical features and connections with motor and nonmotor symptoms (10), diagnostic criteria (5), and therapeutic options (24). Items were assessed by a panel of 37 experts (neurologists, psychiatrists, and a geriatrist), and consensus was achieved in 81.6% of them. Depressive symptoms, enhanced by multiple patient circumstances, were considered Parkinson’s disease risk factors but not clinical indicators of motor symptom and disease progression. These patients should be systematically screened for depression while ruling out both anhedonia and apathy symptoms as they are not necessarily linked to it. Clinical scales (mainly the Geriatric Depression Scale GDS-15) can help establishing the diagnosis of depression, the symptoms of which will require treatment regardless of severity. Efficacious and well-tolerated pharmacological options for Parkinson’s comorbid depression were selective serotonin reuptake inhibitors (especially sertraline), dual-action serotonin and norepinephrine reuptake inhibitors (venlafaxine, desvenlafaxine, and duloxetine), multimodal (vortioxetine, bupropion, mirtazapine, and tianeptine), and anti-Parkinsonian dopamine agonists (pramipexole, ropinirole, and rotigotine). Tricyclic antidepressants and combining type B monoamine oxidase inhibitors with serotonergic drugs have serious side effects in these patients and therefore should not be prescribed. Electroconvulsive therapy was indicated for severe and drug-refractory cases. Cognitive behavioural therapy was recommended in cases of mild depression. Results presented here are useful diagnostic and patient management guidance for other physicians and important considerations to improve future drug trial design.

Motor Symptom Progression and Memory Deficits in Parkinson's Disease

2010 ◽  
Author(s):  
Phuong M. Chau ◽  
Kelly E. Lyons ◽  
Douglas R. Denney ◽  
Rajesh Pahwa ◽  
Brenda Hanna-Pladdy
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Memory Deficits ◽  
Motor Symptom ◽  
Symptom Progression

Diet Quality and Risk of Parkinson’s Disease: A Prospective Study and Meta-Analysis

2020 ◽  
pp. 1-11
Author(s):  
Yi-Hsuan Liu ◽  
Gordon L. Jensen ◽  
Muzi Na ◽  
Diane C. Mitchell ◽  
G. Craig Wood ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cohort Study ◽  
Confidence Intervals ◽  
Diet Quality ◽  
Dietary Pattern ◽  
Disease Risk ◽  
Meta Analysis ◽  
Cox Proportional Hazards ◽  
Healthy Dietary Pattern

Background: Several dietary components have been shown to be neuroprotective against risk of neurodegeneration. However, limited observational studies have examined the role of overall diet quality on risk of Parkinson’s disease. Objectives: We examined the associations between diet quality and risk of Parkinson’s disease in a prospective cohort study and meta-analysis. Methods: Included in the cohort study were 3,653 participants (1,519 men and 2,134 women; mean age: 81.5 years) in the Geisinger Rural Aging Study longitudinal cohort in Pennsylvania. Diet quality was assessed using a validated dietary screening tool containing 25 food- and behavior-specific questions in 2009. Potential Parkinson’s cases were identified using electronic health records based on ICD9 (332.*), ICD10 (G20), and Parkinson-related treatments. Hazard ratios (HRs) and 95% confidence intervals (CIs) across diet quality tertiles were calculated using Cox proportional hazards models after adjusting for potential confounders. We further performed a meta-analysis by pooling our study with four published papers on this topic. Random-effects model was utilized to calculate the pooled risk ratios and 95% confidence intervals (CIs). Results: During a mean of 6.94 years of follow-up, 47 incident Parkinson’s cases were documented. Having high diet quality at baseline was associated with lower Parkinson’s disease risk (adjusted HR for the highest vs the lowest diet quality tertile = 0.39; 95% CI: 0.17, 0.89; p-trend = 0.02). The meta-analysis including 140,617 individuals also showed that adherence to high diet quality or a healthy dietary pattern was associated with lower risk of Parkinson’s disease (pooled risk ratio = 0.64; 95% CI: 0.49, 0.83). Conclusion: Having high diet quality or a healthy dietary pattern was associated with lower future risk of Parkinson’s disease.

scholarly journals Milk and Fermented Milk Intake and Parkinson’s Disease: Cohort Study

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2763
Author(s):  
Erika Olsson ◽  
Liisa Byberg ◽  
Jonas Höijer ◽  
Lena Kilander ◽  
Susanna C. Larsson
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cohort Study ◽  
Proportional Hazards ◽  
Fermented Milk ◽  
Cox Proportional Hazards ◽  
Milk Intake ◽  
Milk Consumption ◽  
Hazard Ratios ◽  
Increased Risk

Milk and fermented milk consumption has been linked to health and mortality but the association with Parkinson’s disease (PD) is uncertain. We conducted a study to investigate whether milk and fermented milk intakes are associated with incident PD. This cohort study included 81,915 Swedish adults (with a mean age of 62 years) who completed a questionnaire, including questions about milk and fermented milk (soured milk and yogurt) intake, in 1997. PD cases were identified through linkage with the Swedish National Patient and Cause of Death Registers. Multivariable-adjusted hazard ratios were obtained from Cox proportional hazards regression models. During a mean follow-up of 14.9 years, 1251 PD cases were identified in the cohort. Compared with no or low milk consumption (<40 mL/day), the hazard ratios of PD across quintiles of milk intake were 1.29 (95% CI 1.07, 1.56) for 40–159 mL/day, 1.19 (95% CI 0.99, 1.42) for 160–200 mL/day, 1.29 (95% CI 1.08, 1.53) for 201–400 mL/day, and 1.14 (95% CI 0.93, 1.40) for >400 mL/day. Fermented milk intake was not associated with PD. We found a weak association between milk intake and increased risk of PD but no dose–response relationship. Fermented milk intake was not associated with increased risk of PD.

scholarly journals Evolution of Apathy in Early Parkinson's Disease: A 4-Years Prospective Cohort Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Ruwei Ou ◽  
Junyu Lin ◽  
Kuncheng Liu ◽  
Zheng Jiang ◽  
Qianqian Wei ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Proportional Hazards ◽  
Rating Scale ◽  
Early Stage ◽  
Cox Proportional Hazards ◽  
Lars Score ◽  
Disease Rating ◽  
Non Motor Symptoms

Objective: We investigated the prevalence, evolution, associated factors, and risk factors of apathy in a cohort of patients with early-stage Parkinson's disease (PD), who underwent a 4-years prospective follow-up.Methods: This study included 188 patients with PD (baseline disease duration &lt;3 years) who underwent an annual evaluation using the Lille Apathy Rating Scale (LARS). Based on the cut-off value of −21 observed on the LARS, patients were categorized as PD with and without apathy. The generalized estimating equations (GEE) model was utilized to determine the factors associated with apathy, and the Cox proportional-hazards regression model was used to determine the predictors of apathy.Results: Apathy increased from a baseline rate of 18.6–28.8% after 4 years; notably, this rate was not persistent across patients' visits. The LARS score was independently associated with the male sex (B 8.131, p = 0.009), low Frontal Assessment Battery (FAB) scores (B 0.567, p = 0.011), low attention scores on the Montreal Cognitive Assessment (MOCA) test (B 0.217, p = 0.026), high Hamilton Depression Rating Scale (HDRS) scores (B 1.362, p &lt; 0.001), high Unified Parkinson's Disease Rating Scale (UPDRS) part III scores (B 1.147, p &lt; 0.001), and prolonged follow-up time (B 1.785, p = 0.048). A high HDRS score was the only predictor of apathy in PD [hazard ratio (HR) 1.043, p = 0.026].Conclusions: The risk of apathy is higher in men with progressive PD accompanied by disease-specific motor and non-motor symptoms. Depression during early-stage PD is a primary risk factor for apathy in PD.

scholarly journals APOE and MAPT Are Associated With Dementia in Neuropathologically Confirmed Parkinson's Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Jon-Anders Tunold ◽  
Hanneke Geut ◽  
J. M. Annemieke Rozemuller ◽  
Sandra Pilar Henriksen ◽  
Mathias Toft ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Decline ◽  
Proportional Hazards ◽  
Age At Onset ◽  
Cox Proportional Hazards ◽  
Postmortem Brain ◽  
Tissue Samples ◽  
Postmortem Brain Tissue ◽  
Ε4 Allele

Introduction: Cognitive decline and dementia are common and debilitating non-motor phenotypic features of Parkinson's disease with a variable severity and time of onset. Common genetic variation of the Apolipoprotein E (APOE) and micro-tubule associated protein tau (MAPT) loci have been linked to cognitive decline and dementia in Parkinson's disease, although studies have yielded mixed results. To further elucidate the influence of APOE and MAPT variability on dementia in Parkinson's disease, we genotyped postmortem brain tissue samples of clinically and pathologically well-characterized Parkinson's donors and performed a survival analysis of time to dementia.Methods: We included a total of 152 neuropathologically confirmed Parkinson's disease donors with or without clinical dementia during life. We genotyped known risk variants tagging the APOE ε4 allele and MAPT H1/H2 inversion haplotype. Cox proportional hazards regression analyses adjusted for age at onset, sex and genetic principal components were performed to assess the association between the genetic variants and time from motor onset to onset of dementia.Results: We found that both the APOE ε4 allele (HR 1.82, 95 % CI 1.16–2.83, p = 0.009) and MAPT H1-haplotype (HR 1.71, 95 % CI 1.06–2.78, p = 0.03) were associated with earlier development of dementia in patients with Parkinson's disease.Conclusion: Our results provide further support for the importance of APOE ε4 and MAPT H1-haplotype in the etiology of Parkinson's disease dementia, with potential future relevance for risk stratification and patient selection for clinical trials of therapies targeting cognitive decline in Parkinson's disease.

scholarly journals Cognitive impairment and levodopa induced dyskinesia in Parkinson’s disease: a longitudinal study from the PACOS cohort

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Antonina Luca ◽  
Roberto Monastero ◽  
Roberta Baschi ◽  
Calogero Edoardo Cicero ◽  
Giovanni Mostile ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Study Cohort ◽  
Level Ii ◽  
Neuropsychological Predictors ◽  
Neuropsychological Evaluations

AbstractAim of the study was to evaluate possible associations between cognitive dysfunctions and development of Levodopa Induced Dyskinesia (LID). PD patients from the Parkinson’s disease Cognitive impairment Study cohort who underwent a baseline and follow-up neuropsychological evaluations were enrolled. Mild Cognitive Impairment (PD-MCI) was diagnosed according to MDS level II criteria. The following cognitive domains were evaluated: episodic memory, attention, executive function, visuo-spatial function and language. A domain was considered as impaired when the subject scored 2 standard deviation below normality cut-off values in at least one test for each domain. Levodopa equivalent dose, UPDRS-ME and LID were recorded at baseline and follow-up. To identify possible neuropsychological predictors associated with the probability of LID development at follow-up, Cox proportional-hazards regression model was used. Out of 139 PD patients enrolled (87 men, mean age 65.7 ± 9.4), 18 (12.9%) were dyskinetic at baseline. Out of 121 patients non-dyskinetic at baseline, 22 (18.1%) developed LID at follow-up. The impairment of the attention and executive domains strongly predicted the development of LID (HR 4.45;95%CI 1.49–13.23 and HR 3.46; 95%CI 1.26–9.48 respectively). Impairment of the attention and executive domains increased the risk of dyskinesia reflecting the alteration of common cortical network.

scholarly journals Evaluation of the association between periodontitis and risk of Parkinson’s disease: a nationwide retrospective cohort study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eunkyung Jeong ◽  
Jun-Beom Park ◽  
Yong-Gyu Park
Keyword(s):  
Parkinson’S Disease ◽  
Metabolic Syndrome ◽  
Parkinson's Disease ◽  
South Korea ◽  
Large Scale ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model

AbstractThe objective of this study was to examine the association between periodontitis and risk of incident Parkinson’s disease using large-scale cohort data on the entire population of South Korea. Health checkup data from 6,856,180 participants aged 40 and older were provided by the National Health Insurance Service of South Korea between January 1, 2009, and December 31, 2009, and the data were followed until December 31, 2017. The hazard ratio (HR) of Parkinson’s disease and 95% confidence interval (CI) were estimated using a Cox proportional hazards model adjusted for potential confounders. The incidence probability of Parkinson’s disease was positively correlated with the presence of periodontitis. The HR of Parkinson’s disease for the participants without the need of further dentist visits was 0.96 (95% CI 0.921–1.002); the HR of Parkinson’s disease increased to 1.142 (95% CI 1.094–1.193) for the individuals who needed further dentist visits. Compared to individuals without periodontitis and without metabolic syndrome, the HR of incident Parkinson’s disease gradually increased for individuals with periodontitis, with metabolic syndrome, and with both periodontitis and metabolic syndrome. People with periodontitis and metabolic syndrome had the highest HR of incident Parkinson’s disease, at 1.167 (95% CI 1.118–1.219). In conclusion, a weak association between periodontitis and Parkinson’s disease was suggested after adjusting for confounding factors from the population-based large-scale cohort of the entire South Korean population.

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