Younger age at onset of sporadic Parkinson’s disease among subjects occupationally exposed to metals and pesticides

ABSTRACT An earlier age at onset of Parkinson’s disease (PD) has been reported to be associated with occupational exposures to manganese and hydrocarbon solvents suggesting that exposure to neurotoxic chemicals may hasten the progression of idiopathic PD. In this study the role of occupational exposure to metals and pesticides in the progression of idiopathic PD was assessed by looking at age at disease onset. The effects of heritable genetic risk factors, which may also influence age at onset, was minimized by including only sporadic cases of PD with no family history of the disease (n=58). Independent samples Student t-test revealed that subjects with occupational exposure to metals and/or pesticides (n=36) were significantly (p=0.013) younger than unexposed controls (n=22). These subjects were then divided into three groups [high (n=18), low (n=18), and unexposed (n=22)] to ascertain if duration of exposure further influenced age at onset of PD. One-way ANOVA revealed that subjects in the high exposure group were significantly (p=0.0121) younger (mean age: 50.33 years) than unexposed subjects (mean age: 60.45 years). Subjects were also stratified by exposure type (metals vs. pesticides). These results suggest that chronic exposure to metals and pesticides is associated with a younger age at onset of PD among patients with no family history of the disease and that duration of exposure is a factor in the magnitude of this effect.

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Individual and familial characteristics of patients with podoconiosis attending a clinic in Musanze District, Rwanda: A retrospective study

Transactions of the Royal Society of Tropical Medicine and Hygiene ◽

10.1093/trstmh/traa068 ◽

2020 ◽

Vol 114 (12) ◽

pp. 947-953

Author(s):

Jean Paul Bikorimana ◽

Ursin Bayisenge ◽

Tonya Huston ◽

Eugene Ruberanziza ◽

Jean Bosco Mbonigaba ◽

...

Keyword(s):

Retrospective Study ◽

Family History ◽

Age Of Onset ◽

Age At Onset ◽

Disease Onset ◽

Patient Characteristics ◽

Health Concern ◽

Red Clay ◽

Younger Age ◽

History Of

Abstract Background Podoconiosis is a progressive swelling of the legs affecting genetically susceptible people who live in areas with irritant red clay soils and walk barefoot. The disease is a public health concern in many countries, including Rwanda. Methods This retrospective study described individual and familial characteristics of patients with podoconiosis attending the Heart and Sole Africa (HASA) clinics in Rwanda. Data on patient characteristics and family history were retrieved from electronic medical records (January 2013 – August 2019). A multiple regression analysis was used to explore factors influencing age of onset of podoconiosis. Results Among 467 patients with podoconiosis, the mean (standard deviation) age of onset was 34.4 (19.6) years, 139 (29.8%) patients developed podoconiosis at <20 years of age, 417 (89%) came from Musanze or neighboring Burera Districts, and 238 (51.0%) had a family history of podoconiosis. Increasing patient age was associated with older age at onset of disease (p<0.001), while an increased number of relatives with podoconiosis (p<0.002) was significantly associated with earlier disease onset. Conclusion Most patients with podoconiosis were women, and more than half had a family history of podoconiosis. An increased number of relatives with podoconiosis was associated with a significantly younger age at disease onset.

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Hunting for Familial Parkinson’s Disease Mutations in the Post Genome Era

Genes ◽

10.3390/genes12030430 ◽

2021 ◽

Vol 12 (3) ◽

pp. 430

Author(s):

Steven R. Bentley ◽

Ilaria Guella ◽

Holly E. Sherman ◽

Hannah M. Neuendorf ◽

Alex M. Sykes ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Family History ◽

Rare Variants ◽

Strong Family History ◽

Disease Mutations ◽

Whole Exome ◽

History Of ◽

Functional Consequences ◽

Multiplex Families

Parkinson’s disease (PD) is typically sporadic; however, multi-incident families provide a powerful platform to discover novel genetic forms of disease. Their identification supports deciphering molecular processes leading to disease and may inform of new therapeutic targets. The LRRK2 p.G2019S mutation causes PD in 42.5–68% of carriers by the age of 80 years. We hypothesise similarly intermediately penetrant mutations may present in multi-incident families with a generally strong family history of disease. We have analysed six multiplex families for missense variants using whole exome sequencing to find 32 rare heterozygous mutations shared amongst affected members. Included in these mutations was the KCNJ15 p.R28C variant, identified in five affected members of the same family, two elderly unaffected members of the same family, and two unrelated PD cases. Additionally, the SIPA1L1 p.R236Q variant was identified in three related affected members and an unrelated familial case. While the evidence presented here is not sufficient to assign causality to these rare variants, it does provide novel candidates for hypothesis testing in other modestly sized families with a strong family history. Future analysis will include characterisation of functional consequences and assessment of carriers in other familial cases.

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Family history of hand tremor in patients with early Parkinson’s disease

Journal of Clinical Neuroscience ◽

10.1016/j.jocn.2021.05.041 ◽

2021 ◽

Vol 90 ◽

pp. 161-164

Author(s):

Seong-Min Choi ◽

Soo Hyun Cho ◽

Kyung Wook Kang ◽

Jae-Myung Kim ◽

Byeong C. Kim

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Family History ◽

Hand Tremor ◽

History Of ◽

Early Parkinson’S Disease

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Parkinson’s disease determinants, prediction and gene–environment interactions in the UK Biobank

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2020-323646 ◽

2020 ◽

Vol 91 (10) ◽

pp. 1046-1054 ◽

Cited By ~ 2

Author(s):

Benjamin Meir Jacobs ◽

Daniel Belete ◽

Jonathan Bestwick ◽

Cornelis Blauwendraat ◽

Sara Bandres-Ciga ◽

...

Keyword(s):

Risk Factors ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Family History ◽

Genetic Risk ◽

Positive Family History ◽

Risk Scores ◽

Uk Biobank ◽

Gene Environment ◽

History Of

ObjectiveTo systematically investigate the association of environmental risk factors and prodromal features with incident Parkinson’s disease (PD) diagnosis and the interaction of genetic risk with these factors. To evaluate whether existing risk prediction algorithms are improved by the inclusion of genetic risk scores.MethodsWe identified individuals with an incident diagnosis of PD (n=1276) and controls (n=500 406) in UK Biobank. We determined the association of risk factors with incident PD using adjusted logistic regression models. We constructed polygenic risk scores (PRSs) using external weights and selected the best PRS from a subset of the cohort (30%). The PRS was used in a separate testing set (70%) to examine gene–environment interactions and compare predictive models for PD.ResultsStrong evidence of association (false discovery rate <0.05) was found between PD and a positive family history of PD, a positive family history of dementia, non-smoking, low alcohol consumption, depression, daytime somnolence, epilepsy and earlier menarche. Individuals with the highest 10% of PRSs had increased risk of PD (OR 3.37, 95% CI 2.41 to 4.70) compared with the lowest risk decile. A higher PRS was associated with earlier age at PD diagnosis and inclusion of the PRS in the PREDICT-PD algorithm led to a modest improvement in model performance. We found evidence of an interaction between the PRS and diabetes.InterpretationHere, we used UK Biobank data to reproduce several well-known associations with PD, to demonstrate the validity of a PRS and to demonstrate a novel gene–environment interaction, whereby the effect of diabetes on PD risk appears to depend on background genetic risk for PD.

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Occupational Exposures and Neurodegenerative Diseases—A Systematic Literature Review and Meta-Analyses

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16030337 ◽

2019 ◽

Vol 16 (3) ◽

pp. 337 ◽

Cited By ~ 20

Author(s):

Lars-Gunnar Gunnarsson ◽

Lennart Bodin

Keyword(s):

Alzheimer’S Disease ◽

Parkinson’S Disease ◽

Alzheimer's Disease ◽

Parkinson's Disease ◽

Occupational Exposure ◽

Neurodegenerative Diseases ◽

Meta Analysis ◽

Occupational Exposures ◽

Increased Risk ◽

Meta Analyses

Objectives: To carry out an integrated and stratified meta-analysis on occupational exposure to electromagnetic fields (EMFs), metals and pesticides and its effects on amyotrophic lateral sclerosis (ALS) and Parkinson’s and Alzheimer’s disease, and investigate the possibility of publication bias. Methods: In the current study, we updated our recently published meta-analyses on occupational exposures in relation to ALS, Alzheimer’s and Parkinson’s disease. Based on 66 original publications of good scientific epidemiological standard, according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) guidelines, we analysed subgroups by carrying out stratified meta-analyses on publication year, statistical precision of the relative risk (RR) estimates, inspection of the funnel plots and test of bias. Results: Based on 19 studies the weighted RR for occupational exposure to EMFs was 1.26 (95% confidence interval (CI) 1.07–1.50) for ALS, 1.33 (95% CI 1.07–1.64) for Alzheimer’s disease and 1.02 (95% CI 0.83–1.26) for Parkinson’s disease. Thirty-one studies concerned occupational exposure to pesticides and the weighted RR was 1.35 (95% CI 1.02–1.79) for ALS, 1.50 (95% CI 0.98–2.29) for Alzheimer’s disease and 1.66 (95% CI 1.42–1.94) for Parkinson’s disease. Finally, 14 studies concerned occupational exposure to metals and only exposure to lead (five studies) involved an elevated risk for ALS or Parkinson’s disease and the weighted RR was 1.57 (95% CI 1.11–2.20). The weighted RR for all the non-lead exposures was 0.97 (95% CI 0.88–1.06). Conclusions: Exposure to pesticides increased the risk of getting the mentioned neurodegenerative diseases by at least 50%. Exposure to lead was only studied for ALS and Parkinson’s disease and involved 50% increased risk. Occupational exposure to EMFs seemed to involve some 10% increase in risk for ALS and Alzheimer’s disease only.

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Factors Influencing Development of Depressive Illness among Parkinson’s Disease Patients

Journal of National Institute of Neurosciences Bangladesh ◽

10.3329/jninb.v5i2.43013 ◽

2019 ◽

Vol 5 (2) ◽

pp. 106-110

Author(s):

Provat Kumar Sarkar ◽

Hasan Zahidur Rahman ◽

Mahua Chandra ◽

Anis Ahmed ◽

Md Enayet Ul Islam ◽

...

Keyword(s):

Diabetes Mellitus ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Family History ◽

Depression Scale ◽

Depressive Illness ◽

Age Group ◽

Cross Sectional ◽

History Of ◽

Axis I

Background: Depressive illness is present among Parkinson’s disease (PD) patients. Objective: The purpose of the present study was to see the influencing factors of development of depressive illness among Parkinson’s disease patients. Methodology: This comparative cross-sectional study was carried out in the Department of Neurology and Department of Psychiatry at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from July 2009 to June 2011 for a period of two (2) years. Parkinson’s disease patients who were attended at the movement disorder clinic and general OPD of Department of Neurology and in-patient department of Neurology at BSMMU, Dhaka were selected as study population. Patients with Parkinson’s plus syndrome, with dementia or other causes of parkinsonism like vascular or drug induced parkinsonism were excluded from this study. Data were collected by filling structured clinical questionnaire, then filling up of ‘structured clinical interview for DSM-IV Axis I disorders’ (SCID-CV) and self-reported ‘Depression scale` questionnaire. Parkinson disease was diagnosed by neurologist by the presence of two or more of the four cardinal criteria namely tremor, rigidity, bradykinesia and postural instability. Then patients were screened for depression by a psychiatrist of Department of Psychiatry at BSMMU, Dhaka. Result: A total of 100 Parkinson’s disease patients were interviewed and 80 patients ultimately participated in the study. The mean age of total Parkinson’s disease patients was 57.71±12.36 years ranging from 35 to 82 years with highest percentage (35%) had age group 65 years or above, 28.7% in 55 to 64 years, 22.5% in 45 to 54 years and lowest percentage (13.8%) in age group less than 45 years. Among 80 Parkinson’s disease patients, depression was present in 34 (42%) patients and was absent in 46 (58%) patients. Diabetes mellitus (p=0.125), hypertension (p=0.097), hypothyroidism (p=1.000), other illness (p=0.595), family history of PD (p=0.758) and levodopa use (p=0.661) were not significantly associated with the development of depressive illness in Parkinson’s disease. Conclusion: Diabetes mellitus (DM), hypertension (HTN), hypothyroidism, other illness, family history of PD and levodopa use do not significantly influence in the development of depressive illness among the Parkinson’s disease. Journal of National Institute of Neurosciences Bangladesh, 2019;5(2): 106-110

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Genetic Insights into Early-onset Parkinson’s Disease

US Neurology ◽

10.17925/usn.2010.06.01.41 ◽

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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Socio-demographic risk factors associated with febrile seizures at Puducherry: a retrospective study

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20201653 ◽

2020 ◽

Vol 7 (5) ◽

pp. 1130

Author(s):

Gobinaath . ◽

Arun Daniel J.

Keyword(s):

Risk Factors ◽

Family History ◽

Age At Onset ◽

Febrile Seizures ◽

Factors Associated ◽

Younger Age ◽

History Of ◽

Demographic Risk ◽

Tract Infections ◽

Demographic Risk Factors

Background: Febrile seizures occur commonly in the under 5 age group and is associated with few risk factors causing its recurrence like very high fever, family history of seizures, low sodium levels and younger age of onset which are subject to seasonal and wide geographical variations. This study aimed at detecting the major risk factors associated with recurrent febrile seizures in an Indian population.Methods: A retrospective hospital-based study was conducted among a total of 300 cases aged 6 months to 5 years attending to the paediatric OPD with history of fever followed by febrile seizures. Information regarding socio-demographic and clinical variables associated with febrile seizure was collected and analyzed.Results: The mean age of the study participants was 25.6±2.2 months and majority (60%) were males. Family history of seizures was present in 25.3% (n=76) of the children with febrile seizures. Respiratory infections (73.3%) and gastroenteritis (17%) were the major infective reasons associated with the occurrence of febrile seizures followed by pneumonia (6.3%) and urinary tract infections (5%). Recurrence of FS was significantly higher among the children with family history of FS (p=0.009), age at onset lesser (p<0.001) and simple FS seizures.Conclusions: Younger age at onset and positive family history of seizures were important socio-demographic risk factors associated with recurrent febrile seizures.

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