GI infections are associated with an increased risk of Parkinson’s disease

Abstract Objective Research has identified common genetic influences on handedness and neurological/mental health phenotypes. It also has been shown there may be increased risk for development of neurological disorders/diseases among individuals naturally left-handed or demonstrating non-right-hand preference. This investigation examined prevalence of right-handed versus non-right-handed individuals with Parkinson’s disease (PD) compared to controls. Method Participants were 264 patients with PD (mean age = 69.83 years) and 256 control volunteers (mean age = 71.42 years). Mean Dementia Rating Scale composites for the groups were 123.68 and 136.00, respectively. Participants self-identified their dominant hand for writing and usage was confirmed during the session. Results Proportions of non-right- and right-handed controls (7.0% and 93.0%) versus individuals with PD (6.8% and 93.2%) did not differ. Changes in proportions of non-right- and right-handedness across age ranges were not significant for controls or patients. There was a trend for a larger proportion of women (55.9%) versus men among controls (44.1%), □ 2 (1) = 3.29, p < .10; whereas, the proportion of men (64.4%) with PD was larger than that of women. (35.6%), □ 2 (1) = 21.31, p < .001. For controls and patients, non-right and right handedness gender proportions were similar. Conclusions This study is the first to assess handedness prevalence rates in PD. Results suggest prevalence of non-right handedness is similar in PD and healthy individuals and does not appear to differ markedly by gender or with advancing age. The occurrence of a trend for a larger proportion of women than men among controls is consistent with census-based statistics.

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Migraine is related to an increased risk of Parkinson’s disease: A population-based, propensity score-matched, longitudinal follow-up study

Cephalalgia ◽

10.1177/0333102416630577 ◽

2016 ◽

Vol 36 (14) ◽

pp. 1316-1323 ◽

Cited By ~ 10

Author(s):

Hsin-I Wang ◽

Yu-Chun Ho ◽

Ya-Ping Huang ◽

Shin-Liang Pan

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Survival Rate ◽

Propensity Score ◽

Population Based ◽

Free Survival ◽

Follow Up Study ◽

Increased Risk ◽

Migraine Group

Background The association between migraine and Parkinson’s disease (PD) remains controversial. The purpose of the present population-based, propensity score-matched follow-up study was to investigate whether migraineurs are at a higher risk of developing PD. Methods A total of 41,019 subjects aged between 40 and 90 years with at least two ambulatory visits with a diagnosis of migraine in 2001 were enrolled in the migraine group. A logistic regression model that included age, sex, pre-existing comorbidities and socioeconomic status as covariates was used to compute the propensity score. The non-migraine group consisted of 41,019 propensity score-matched, randomly sampled subjects without migraine. The PD-free survival rate were estimated using the Kaplan–Meier method. Stratified Cox proportional hazard regression was used to estimate the effect of migraine on the risk of developing PD. Results During follow-up, 148 subjects in the migraine group and 101 in the non-migraine group developed PD. Compared to the non-migraine group, the hazard ratio of PD for the migraine group was 1.64 (95% confidence interval: 1.25–2.14, p = 0.0004). The PD-free survival rate for the migraine group was significantly lower than that for the non-migraine group ( p = 0.0041). Conclusions This study showed an increased risk of developing PD in patients with migraine.

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Increased risk of overactive bladder in patients with idiopathic Parkinson’s disease: Insight from a nationwide population-based cohort study

PLoS ONE ◽

10.1371/journal.pone.0193783 ◽

2018 ◽

Vol 13 (3) ◽

pp. e0193783 ◽

Cited By ~ 2

Author(s):

Fu-Yu Lin ◽

Yi-Chien Yang ◽

Cheng-Li Lin ◽

Lukas Jyuhn-Hsiarn Lee

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cohort Study ◽

Overactive Bladder ◽

Population Based ◽

Idiopathic Parkinson’S Disease ◽

Idiopathic Parkinson's Disease ◽

Increased Risk

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Dietary intake of folate, vitamin B6, vitamin B12 and riboflavin and risk of Parkinson's disease: a case–control study in Japan

British Journal Of Nutrition ◽

10.1017/s0007114510001005 ◽

2010 ◽

Vol 104 (5) ◽

pp. 757-764 ◽

Cited By ~ 41

Author(s):

Kentaro Murakami ◽

Yoshihiro Miyake ◽

Satoshi Sasaki ◽

Keiko Tanaka ◽

Wakaba Fukushima ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Dietary Intake ◽

Case Control Study ◽

Case Control ◽

B Vitamins ◽

Vitamin B ◽

Increased Risk ◽

The Uk ◽

Control Study

Increased homocysteine levels might accelerate dopaminergic cell death in Parkinson's disease (PD) through neurotoxic effects; thus, increasing intake of B vitamins involved in the regulation of homocysteine metabolism might decrease the risk of PD through decreasing plasma homocysteine. However, epidemiological evidence for the association of dietary B vitamins with PD is sparse, particularly in non-Western populations. We conducted a hospital-based case–control study in Japan to examine associations between dietary intake of folate, vitamin B6, vitamin B12 and riboflavin and the risk of PD. Patients with PD diagnosed using the UK PD Society Brain Bank criteria (n 249) and controls without neurodegenerative diseases (n 368) were recruited. Dietary intake during the preceding month was assessed at the time of study recruitment using a validated, self-administered, semi-quantitative, comprehensive diet history questionnaire. After adjustment for potential dietary and non-dietary confounding factors, intake of folate, vitamin B12 and riboflavin was not associated with the risk of PD (P for trend = 0·87, 0·70 and 0·11, respectively). However, low intake of vitamin B6 was associated with an increased risk of PD, independent of potential dietary and non-dietary confounders. Multivariate OR (95 % CI) for PD in the first, second, third and fourth quartiles of vitamin B6 were 1 (reference), 0·56 (0·33, 0·94), 0·69 (0·38, 1·25) and 0·48 (0·23, 0·99), respectively (P for trend = 0·10). In conclusion, in the present case–control study in Japan, low intake of vitamin B6, but not of folate, vitamin B12 or riboflavin, was independently associated with an increased risk of PD.

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The “Gender Factor” in Wearing-Off among Patients with Parkinson’s Disease: A Post Hoc Analysis of DEEP Study

The Scientific World JOURNAL ◽

10.1155/2015/787451 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 20

Author(s):

Delia Colombo ◽

Giovanni Abbruzzese ◽

Angelo Antonini ◽

Paolo Barone ◽

Gilberto Bellia ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cross Sectional Study ◽

Motor Symptom ◽

Cross Sectional ◽

Post Hoc Analysis ◽

Increased Risk ◽

Wearing Off ◽

Gender Factor ◽

Post Hoc

Background. The early detection of wearing-off in Parkinson disease (DEEP) observational study demonstrated that women with Parkinson’s disease (PD) carry an increased risk (80.1%) for wearing-off (WO). This post hoc analysis of DEEP study evaluates gender differences on WO and associated phenomena.Methods. Patients on dopaminergic treatment for ≥1 year were included in this multicenter observational cross-sectional study. In a single visit, WO was diagnosed based on neurologist assessment as well as the use of the 19-item wearing-off questionnaire (WOQ-19); WO was defined for scores ≥2. Post hoc analyses were conducted to investigate gender difference for demographic and clinical features with respect to WO.Results. Of 617 patients enrolled, 236 were women and 381 were men. Prevalence of WO was higher among women, according to both neurologists’ judgment (61.9% versus 53.8%,P=0.045) and the WOQ-19 analysis (72.5% versus 64.0%,P=0.034). In patients with WO (WOQ-19), women experienced ≥1 motor symptom in 72.5% versus 64.0% in men and ≥1 nonmotor symptom in 44.5% versus 36.7%, in men.Conclusions. Our results suggest WO as more common among women, for both motor and nonmotor symptoms. Prospective studies are warranted to investigate this potential gender-effect.

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Predictors of Pharyngeal Dysphagia in Patients with Parkinson’s Disease

Journal of Parkinson s Disease ◽

10.3233/jpd-202081 ◽

2020 ◽

Vol 10 (4) ◽

pp. 1727-1735

Author(s):

Inga Claus ◽

Paul Muhle ◽

Judith Suttrup ◽

Bendix Labeit ◽

Sonja Suntrup-Krueger ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Logistic Regression ◽

Rating Scale ◽

Equivalent Dose ◽

Binary Logistic Regression Analysis ◽

Screening Methods ◽

Clinical Predictors ◽

Pharyngeal Dysphagia ◽

Increased Risk

Background: Diagnosis of pharyngeal dysphagia in patients with Parkinson’s disease is often difficult as reliable screening methods are lacking so far and clinical examination fails to adequately assess the pharyngeal phase of swallowing. Objective: To identify clinical predictors indicating the presence of pharyngeal dysphagia in patients at risk. Methods: We examined pharyngeal dysphagia in a large cohort of patients with Parkinson’s disease (n = 200) divided in three clinical subtypes (tremor-dominant (TD), mainly bradykinetic (BK) and early postural instability and gait difficulty PIGD)) by using flexible endoscopic evaluation of swallowing. ANOVA-multivariance analysis and following t-tests as well as binary logistic regression analysis were performed to detect group differences and to identify clinical predictors for dysphagia. Results: Statistically significant differences were found in the dysphagic group: age, male gender, disease duration, stage of the disease, Levodopa equivalent dose and higher scores on the Unified Parkinson’s disease rating scale III and II, item 7. The PIGD subtype was affected more frequently than the TD and BK subtype. In a logistic regression model higher age (>63.5 years p < 0.05) and Levodopa equivalent dose (>475 mg, p < 0.01) were identified to be independent predictors for the presence of pharyngeal dysphagia. Conclusion: Particularly patients with an age > 63.5 years and a daily Levodopa equivalent dose >475 mg show an increased risk for pharyngeal dysphagia. These findings may partly be influenced by presbyphagia but are likely to represent disease progression. The PIGD subtype seems to be a risk factor due to more pronounced dyscoordination of oropharyngeal muscle movements.

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A pH-eQTL interaction at the RIT2-SYT4 Parkinson's disease risk locus in the substantia nigra

10.1101/2020.12.16.423140 ◽

2020 ◽

Author(s):

Sejal Patel ◽

Derek Howard ◽

Leon French

Keyword(s):

Gene Expression ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Substantia Nigra ◽

Human Brain ◽

Disease Risk ◽

Brain Regions ◽

Dopamine Neurons ◽

Postmortem Human Brain ◽

Increased Risk

BACKGROUND: Parkinson's disease (PD) causes severe motor and cognitive disabilities that result from the progressive loss of dopamine neurons in the substantia nigra. The rs12456492 variant in the RIT2 gene has been repeatedly associated with increased risk for Parkinson's disease. From a transcriptomic perspective, a meta-analysis found that RIT2 gene expression is correlated with pH in the human brain. OBJECTIVE: To assess pH associations at the RIT2-SYT4 locus. METHODS: Linear models to examine two datasets that assayed rs12456492, gene expression, and pH in the postmortem human brain. RESULTS: Using the BrainEAC dataset, we replicate the positive correlation between RIT2 gene expression and pH in the human brain. Furthermore, we found that the relationship between expression and pH is influenced by rs12456492. When tested across ten brain regions, this interaction is specifically found in the substantia nigra. A similar association was found for the co-localized SYT4 gene. In addition, SYT4 associations are stronger in a combined model with both genes, and the SYT4 interaction appears to be specific to males. In the GTEx dataset, the pH associations involving rs12456492 and expression of either SYT4 and RIT2 was not seen. This null finding may be due to the short postmortem intervals (PMI) of the GTEx tissue samples. In the BrainEAC data, we tested the effect of PMI and only observed the interactions in the longer PMI samples. CONCLUSIONS: These previously unknown associations suggest novel mechanistic roles for rs12456492, RIT2, and SYT4 in the regulation of pH in the substantia nigra.

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Study of The Collagen Type VI Alpha 3 (COL6A3) Gene in Parkinson’s Disease

10.21203/rs.3.rs-210101/v1 ◽

2021 ◽

Author(s):

Chong-Yao Jin ◽

Ran Zheng ◽

Zhi-Hao Lin ◽

Nai-Jia Xue ◽

Ying Chen ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Collagen Type ◽

Gene Mutations ◽

Compound Heterozygous ◽

Genetic Characteristics ◽

Increased Risk ◽

Collagen Type Vi ◽

Chinese Cohort ◽

Aggregate Burden

Abstract Background To date, the genetic contribution to Parkinson’s disease (PD) remains unclear. Mutations in the collagen type VI alpha 3 (COL6A3) gene were recently identified as a cause of isolated dystonia. Since PD and dystonia are closely related disorders with shared clinical and genetic characteristics, we explored the association between COL6A3 and PD in a Chinese cohort. Methods We performed genetic screening of COL6A3 in a Chinese cohort of 173 patients with sporadic PD and 200 healthy controls. We identified variants that are likely to have pathogenic effects based on: 1) a minor allele frequency of < 0.01; and 2) the variant being recognized as deleterious by at least 15 different in silico predicting tools. Finally, we tested the aggregate burden of COL6A3 on PD via SKAT-O analysis. Results First, we found compound heterozygous COL6A3 gene mutations in one early-onset PD patients. Then, we explored whether COL6A3 variants contributed to increased risk of developing PD in a Chinese population. We detected 21 rare non-synonymous variants. Pathogenicity predictions identified seven novel non-synonymous variants as likely to be pathogenic. SKAT-O analysis further revealed that an aggregate burden of variants in COL6A3 contributes to PD (p = 0.03). Conclusion An increased aggregate burden of the COL6A3 gene was detected in patients with PD.

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Multiple genetic pathways regulating lifespan extension are neuroprotective in a G2019S LRRK2 nematode model of Parkinson’s disease

10.1101/2020.07.06.190025 ◽

2020 ◽

Author(s):

Megan M. Senchuk ◽

Jeremy M. Van Raamsdonk ◽

Darren J. Moore

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Late Onset ◽

Lifespan Extension ◽

Disease Manifestation ◽

Genetic Pathways ◽

Dopaminergic Neurodegeneration ◽

Age Related ◽

Increased Risk ◽

Extended Longevity

AbstractBackgroundMutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most frequent cause of late-onset, familial Parkinson’s disease (PD), and LRRK2 variants are associated with increased risk for sporadic PD. While advanced age represents the strongest risk factor for disease development, it remains unclear how different age-related pathways interact to regulate LRRK2-driven late-onset PD.FindingsIn this study, we employ a C.elegans model expressing PD-linked G2019S LRRK2 to examine the interplay between age-related pathways and LRRK2-induced dopaminergic neurodegeneration. We find that multiple genetic pathways that regulate lifespan extension can provide robust neuroprotection against mutant LRRK2. However, the level of neuroprotection does not strictly correlate with the magnitude of lifespan extension, suggesting that lifespan can be experimentally dissociated from neuroprotection. Using tissue-specific RNAi, we demonstrate that lifespan-regulating pathways, including insulin/IGF-1 signaling, TOR, and mitochondrial respiration, can be directly manipulated in neurons to mediate neuroprotection. We extend this finding for AGE-1/PI3K, where pan-neuronal versus dopaminergic neuronal restoration of AGE-1 reveals both cell-autonomous and non-cell-autonomous neuroprotective mechanisms downstream of insulin signaling.ConclusionsOur data demonstrate the importance of distinct lifespan-regulating pathways in the pathogenesis of LRRK2-linked PD, and suggest that extended longevity is broadly neuroprotective via the actions of these pathways at least in part within neurons. This study further highlights the complex interplay that occurs between cells and tissues during organismal aging and disease manifestation.

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