Risk Factors for Psychosis in Parkinson’s Disease

Psychosis is a characteristic neuropsychiatric symptom of Parkinson’s disease (PD) that is common and associated with worse outcomes. The purpose of this article is to review identified risk factors for visual hallucinations in PD, the most common manifestation of psychosis. With the possible exception of dopamine agonists, antiparkinsonian medications are only considered modifiers of psychosis in PD. Dementia in PD has consistently been shown to be associated with psychosis, and executive dysfunction and impairment in visual processing appear to play a role in its pathogenesis. The association of psychosis with disorders of sleep–wake dysregulation and autonomic dysfunction supports the involvement of brainstem dysfunction in PD psychosis. Despite many studies evaluating genetic risk factors for hallucinations, GBA mutations are the only variants consistently reported to be associated with an increased risk of hallucinations in PD. Lastly, psychosis in PD is associated with a more severe disease burden, both related and unrelated to PD pathology. Any explanatory model of psychosis in PD must incorporate pharmacological, neuroanatomic, pathological, and genetic factors before there can be a complete understanding of this common and disabling neuropsychiatric symptom.

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A Comparative Study of the Behavioral Profile of the Behavioral Variant of Frontotemporal Dementia and Parkinson’s Disease Dementia

Dementia and Geriatric Cognitive Disorders Extra ◽

10.1159/000512042 ◽

2020 ◽

pp. 182-194

Author(s):

Dinesh Saini ◽

Adreesh Mukherjee ◽

Arijit Roy ◽

Atanu Biswas

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Frontotemporal Dementia ◽

Severe Disease ◽

Executive Dysfunction ◽

Behavioral Symptoms ◽

Parkinson’S Disease Dementia ◽

Subcortical Dementia ◽

Behavioral Profile ◽

Cortical Dementia

Background: Executive dysfunction is the common thread between pure cortical dementia like the behavioral variant of frontotemporal dementia (bvFTD) and subcortical dementia like Parkinson’s disease dementia (PDD). Although there are clinical and cognitive features to differentiate cortical and subcortical dementia, the behavioral symptoms differentiating these 2 conditions are still not well known. Objective: To evaluate the behavioral profile of bvFTD and PDD and compare them to find out which behavioral symptoms can differentiate between the two. Methods: Twenty consecutive patients with bvFTD (>1 year after diagnosis) and 20 PDD patients were recruited according to standard diagnostic criteria. Behavioral symptoms were collected from the reliable caregiver by means of a set of questionnaires and then compared between the 2 groups. Results: bvFTD patients had more severe disease and more behavioral symptoms than PDD. bvFTD patients were different from PDD patients due to their significantly greater: loss of basic emotion (p < 0.001, odds ratio [OR] 44.33), loss of awareness of pain (p < 0.001, OR 44.33), disinhibition (p < 0.001, OR 35.29), utilization phenomenon (p = 0.008, OR 22.78), loss of taste discrimination (p < 0.001, OR 17), neglect of hygiene (p = 0.001, OR 13.22), loss of embarrassment (p = 0.003, OR 10.52), wandering (p = 0.004, OR 9.33), pacing (p = 0.014, OR 9), selfishness (p = 0.014, OR 9), increased smoking (p = 0.014, OR 9), increased alcohol consumption (p = 0.031, OR 7.36), social avoidance (p = 0.012, OR 6.93), mutism (p = 0.041, OR 5.67), and failure to recognize objects (p = 0.027, OR 4.33). The bvFTD patients were also significantly less suspicious (p = 0.001, OR 0.0295), less inclined to have a false belief that people were in their home (p = 0.014, OR 0.11) and had fewer visual illusions/hallucinations (p = 0.004, OR 0.107) than PDD patients. Conclusion: Behavioral symptoms are helpful to distinguish bvFTD from PDD, and thus also cortical dementia with frontal-lobe dysfunction from subcortical dementia.

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Dermal fibroblasts from patients with Parkinson’s disease have normal GCase activity and autophagy compared to patients with PD and GBA mutations

F1000Research ◽

10.12688/f1000research.12090.1 ◽

2017 ◽

Vol 6 ◽

pp. 1751 ◽

Cited By ~ 3

Author(s):

Lucy M Collins ◽

Janelle Drouin-Ouellet ◽

Wei-Li Kuan ◽

Timothy Cox ◽

Roger A Barker

Keyword(s):

Risk Factors ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Genetic Risk ◽

Gaucher Disease ◽

Dermal Fibroblasts ◽

Skin Fibroblasts ◽

Autophagic Flux ◽

Clinical Progression ◽

Gba Mutations

Background: Recently, the development of Parkinson’s disease (PD) has been linked to a number of genetic risk factors, of which the most common is glucocerebrosidase (GBA) mutations. Methods: We investigated PD and Gaucher Disease (GD) patient derived skin fibroblasts using biochemistry assays. Results: PD patient derived skin fibroblasts have normal glucocerebrosidase (GCase) activity, whilst patients with PD and GBA mutations have a selective deficit in GCase enzyme activity and impaired autophagic flux. Conclusions: This data suggests that only PD patients with a GBA mutation have altered GCase activity and autophagy, which may explain their more rapid clinical progression.

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Parkinson’s Disease and Symptomatic Osteoarthritis Are Independent Risk Factors of Falls in the Elderly

Clinical Medicine Insights Arthritis and Musculoskeletal Disorders ◽

10.1177/1179544119884936 ◽

2019 ◽

Vol 12 ◽

pp. 117954411988493 ◽

Cited By ~ 2

Author(s):

Anneli Teder-Braschinsky ◽

Aare Märtson ◽

Marika Rosenthal ◽

Pille Taba

Keyword(s):

Risk Factors ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Knee Osteoarthritis ◽

The Elderly ◽

Control Group ◽

Increased Risk ◽

Symptomatic Knee ◽

Risk Of Falls ◽

Risk Factors For Falls

Objectives: Deteriorating functionality and loss of mobility, resulting from Parkinson’s disease, may be worsened by osteoarthritis, which is the most common form of joint disease causing pain and functional impairment. We assessed the association between symptomatic hip or knee osteoarthritis, falls, and the ability to walk among patients with Parkinson’s disease compared to a control group. Methods: A total of 136 patients with Parkinson’s disease in Southern Estonia and 142 controls with an average age of 76.8 and 76.3 years, respectively, were enrolled in a retrospective case-control study. Information on falls and related fractures during the previous year was collected from the patients with Parkinson’s disease and controls. Covariates included gender, age, mobility, duration of Parkinson’s disease, and fractures. Results: Patients with Parkinson’s disease were at an increased risk of falls compared to the control group, and for the higher risk of fractures. Symptomatic knee or hip osteoarthritis was a significant independent predictor of falls in both patients with Parkinson’s disease and controls. The higher risk for fractures during the previous year was demonstrated in symptomatic osteoarthritis. Risk factors for falls included also female gender, use of sleep pills, and the inability to walk 500 m. Conclusions: Symptomatic hip and knee osteoarthritis are risk factors for falls and related fractures among the elderly population with and without Parkinson’s disease. The inability to walk 500 m could be used as a simple predictive factor for the increased risk of falls among elderly populations.

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DJ-1Variants in Indian Parkinson’s Disease Patients

Disease Markers ◽

10.1155/2012/467085 ◽

2012 ◽

Vol 33 (3) ◽

pp. 127-135 ◽

Cited By ~ 9

Author(s):

Tamal Sadhukhan ◽

Arindam Biswas ◽

Shyamal K Das ◽

Kunal Ray ◽

Jharna Ray

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Older Patients ◽

Severe Disease ◽

Gene Products ◽

Eastern India ◽

Deletion Allele ◽

Disease Phenotypes ◽

Increased Risk ◽

Different Populations

Parkinson’s disease (PD) is a common neurodegenerative movement disorder. Among the candidate genes,DJ-1accounts for about 1% of the cases in different populations. We aim to find the contribution of the gene towards PD among Indians. By screeningDJ-1in 308 PD patients of eastern India and 248 ethnically matched controls, a total of 21 nucleotide variants – including two nonsynonymous changes – were detected. p.Arg98Gln was identified in 6 unrelated patients and 2 controls while p.Val35Ile, a novel change, was found only in 2 unrelated patients. A SNP (rs7517357) was observed to be moderately associated with increased risk of PD (p< 0.05). The deletion allele (g.168–185del) of a known 18 bp del/ins/dup polymorphism was found to be over represented (p< 0.05) among older patients (> 40 years) compared to the controls (> 45 years). Two of the patients, also heterozygotes forPINK1mutation, had more severe disease phenotypes, consistent with the reported interaction betweenPINK1andDJ-1gene products [19]. Our results demonstrate that up to 3.9% (12/308) of PD patients of eastern India harborDJ-1variants that should be explored further for any causal relationship with PD.

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Potential Common Genetic Risks of Sporadic Parkinson’s Disease and Amyotrophic Lateral Sclerosis in the Han Population of Mainland China

Frontiers in Neuroscience ◽

10.3389/fnins.2021.753870 ◽

2021 ◽

Vol 15 ◽

Author(s):

Yi Lu ◽

Wenzhi Chen ◽

Caihui Wei ◽

Yu Zhu ◽

Renshi Xu

Keyword(s):

Risk Factors ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Amyotrophic Lateral Sclerosis ◽

Mainland China ◽

Adaptor Protein ◽

Han Population ◽

Increased Risk ◽

Sporadic Parkinson’S Disease ◽

Lateral Sclerosis

Sporadic Parkinson’s disease (sPD) and sporadic amyotrophic lateral sclerosis (sALS) are neurodegenerative diseases characterized by progressive and selective neuron death, with some genetic similarities. In order to investigate the genetic risk factors common to both sPD and sALS, we carried out a screen of risk alleles for sALS and related loci in 530 sPD patients and 530 controls from the Han population of Mainland China (HPMC). We selected 27 single-nucleotide polymorphisms in 10 candidate genes associated with sALS, and we performed allelotyping and genotyping to determine their frequencies in the study population as well as bioinformatics analysis to assess their functional significance in these diseases. The minor alleles of rs17115303 in DAB adaptor protein 1 (DAB1) gene and rs6030462 in protein tyrosine phosphatase receptor type T (PTPRT) gene were correlated with increased risk of both sPD and sALS. Polymorphisms of rs17115303 and rs6030462 were associated with alterations in transcription factor binding sites, secondary structures, long non-coding RNA interactions, and nervous system regulatory networks; these changes involved biological processes associated with neural cell development, differentiation, neurogenesis, migration, axonogenesis, cell adhesion, and metabolism of phosphate-containing compounds. Thus, variants of DAB1 gene (rs17115303) and PTPRT gene (rs6030462) are risk factors common to sPD and sALS in the HPMC. These findings provide insight into the molecular pathogenesis of both diseases and can serve as a basis for the development of targeted therapies.

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Assessment of Parkinson’s Disease symptoms and toxin exposures in firefighters: a cross-sectional survey

10.21203/rs.3.rs-223780/v1 ◽

2021 ◽

Author(s):

Roshni Kotwani ◽

Andrea N. Clapp ◽

Haley E. Huggins ◽

Oceanis Vaou ◽

Anna DePold Hohler

Keyword(s):

Risk Factors ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Behavior Disorder ◽

Muscle Stiffness ◽

Cross Sectional Survey ◽

Cross Sectional ◽

Disease Symptoms ◽

Increased Risk ◽

Toxin Exposure

Abstract BACKGROUND: Parkinson’s disease (PD) has been correlated with several environmental and toxic exposures. The frequency of PD in firefighters is higher than the general population, which may be due to the high amounts of toxin exposures firefighters experience on the job. There is a need to further address the high rates of PD among this subgroup. The purpose of this study is to improve our understanding of the relationship between toxin exposure in firefighters and Parkinson’s Disease symptoms. METHODS: An anonymous survey distributed to Massachusetts firefighters assessed risk factors for toxin exposure and presence of PD symptoms. Risk factors included frequency and duration of time spent firefighting, number of fires worked, and history of toxin exposure (i.e., pesticides). We collected the frequency of PD symptoms including tremors, muscle stiffness, REM behavior disorder, hyposmia, micrographia, and decreased walking pace. Analyses comparing toxin exposure and presence of PD symptoms were performed using Chi-square testing, p < 0.05 was considered significant.RESULTS: Two hundred participants were included in the study. The number of years as a firefighter, the number of days per week working, and the number of fires worked correlated with higher reports of hyposmia, micrographia, and decreased walking pace.CONCLUSION: Firefighters have an increased risk for PD symptoms as a result of the toxin exposures that are frequently present in fires.

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Improving estimation of Parkinson’s disease risk - The enhanced PREDICT-PD algorithm

10.1101/2020.03.16.20037002 ◽

2020 ◽

Author(s):

Jonathan P. Bestwick ◽

Stephen D. Auger ◽

Cristina Simonet ◽

Richard N. Rees ◽

Daniel Rack ◽

...

Keyword(s):

Risk Factors ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Published Data ◽

Likelihood Ratios ◽

Basic Algorithm ◽

Standard Deviation Increase ◽

Risk Estimates ◽

Increased Risk ◽

Incident Cases

ABSTRACTBackgroundWe previously reported a basic algorithm to identify risk of Parkinson’s disease (PD) using published data on risk factors and prodromal features. Using this algorithm, the PREDICT-PD study identified individuals at increased risk of PD, using tapping speed, hyposmia and REM sleep behaviour disorder (RBD) as “intermediate” markers of prodromal PD until sufficient incident cases accrued.ObjectivesTo develop and test an enhanced algorithm which incorporates these intermediate markers into the risk model.MethodsIntermediate markers were incorporated into risk estimates, and likelihood ratios for both the presence and absence of risk factors were used. Risk estimates were compared using the enhanced and the basic algorithm in members of the PREDICT-PD pilot cohort.ResultsThe enhanced PREDICT-PD algorithm yielded a much greater range of risk estimates than the basic algorithm (346 - 784-fold difference between the 10th and 90th centiles vs 10 12-fold respectively). There was a greater increase in risk of PD with increasing risk scores for the enhanced algorithm than for the basic algorithm (hazard ratios per one standard deviation increase in log risk of 2.73 [95% CI 1.68 – 4.45; p<0.001] versus 1.47 [95% CI 0.86 2.51; p=0.16] respectively). Estimates from the enhanced algorithm also correlated more closely with subclinical striatal DaT-SPECT dopamine depletion (R2=0.14, p=0.010 vs R2=0.043, p=0.17).ConclusionsIncorporating the previous intermediate markers of prodromal PD and using likelihood ratios improved the accuracy of the PREDICT-PD prediction algorithm for PD.

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Lifestyle Factors and Parkinson’s Disease Risk in a Rural New England Case-Control Study

Parkinson s Disease ◽

10.1155/2021/5541760 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Angeline S. Andrew ◽

Faith L. Anderson ◽

Stephen L. Lee ◽

Katharine M. Von Herrmann ◽

Matthew C. Havrda

Keyword(s):

Risk Factors ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Head Trauma ◽

Environmental Risk ◽

Case Control Study ◽

Case Control ◽

Environmental Risk Factors ◽

Increased Risk ◽

Control Study

Introduction. Parkinson’s disease (PD) is an age-related neurodegenerative disease likely caused by complex interactions between genetic and environmental risk factors. Exposure to pesticides, toxic metals, solvents, and history of traumatic brain injury have been implicated as environmental risk factors for PD, underscoring the importance of identifying risk factors associated with PD across different communities. Methods. We conducted a questionnaire-based case-control study in a rural area on the New Hampshire/Vermont border, enrolling PD patients and age- and sex-matched controls from the general population between 2017 and 2020. We assessed frequent participation in a variety of recreational and occupational activities and surveyed potential chemical exposures. Results. Suffering from “head trauma or a concussion” prior to diagnosis was associated with a fourfold increased risk of PD. Adjustment for head trauma negated any risk of participation in “strenuous athletic activities.” We observed a 2.7-fold increased risk of PD associated with activities involving lead (adjusted p = 0.038 ). Conclusion. Implicating these factors in PD risk favors public health efforts in exposure mitigation while also motivating future work mechanisms and intervention opportunities.

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Dermal fibroblasts from patients with Parkinson’s disease have normal GCase activity and autophagy compared to patients with PD and GBA mutations

F1000Research ◽

10.12688/f1000research.12090.2 ◽

2018 ◽

Vol 6 ◽

pp. 1751 ◽

Cited By ~ 3

Author(s):

Lucy M Collins ◽

Janelle Drouin-Ouellet ◽

Wei-Li Kuan ◽

Timothy Cox ◽

Roger A Barker

Keyword(s):

Risk Factors ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Genetic Risk ◽

Gaucher Disease ◽

Dermal Fibroblasts ◽

Skin Fibroblasts ◽

Autophagic Flux ◽

Clinical Progression ◽

Gba Mutations

Background: Recently, the development of Parkinson’s disease (PD) has been linked to a number of genetic risk factors, of which the most common is glucocerebrosidase (GBA) mutations. Methods: We investigated PD and Gaucher Disease (GD) patient derived skin fibroblasts using biochemistry assays. Results: PD patient derived skin fibroblasts have normal glucocerebrosidase (GCase) activity, whilst patients with PD and GBA mutations have a selective deficit in GCase enzyme activity and impaired autophagic flux. Conclusions: This data suggests that only PD patients with a GBA mutation have altered GCase activity and autophagy, which may explain their more rapid clinical progression.

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