Rotenone, Paraquat, and Parkinson's Disease Tanner, Caroline M.; Kamel, Freya; Ross, G. Webster ...
Environmental health perspectives,
06/2011, Letnik:
119, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Background: Mitochondrial dysfunction and oxidative stress are pathophysiologic mechanisms implicated in experimental models and genetic forms of Parkinson's disease (PD). Certain pesticides may ...affect these mechanisms, but no pesticide has been definitively associated with PD in humans. Objectives: Our goal was to determine whether pesticides that cause mitochondrial dysfunction or oxidative stress are associated with PD or clinical features of parkinsonism in humans. Methods: We assessed lifetime use of pesticides selected by mechanism in a case–control study nested in the Agricultural Health Study (AHS). PD was diagnosed by movement disorders specialists. Controls were a stratified random sample of all AHS participants frequency-matched to cases by age, sex, and state at approximately three controlsrone case. Results: In 110 PD cases and 358 controls, PD was associated with use of a group of pesticides that inhibit mitochondrial complex I odds ratio (OR) = 1.7; 95% confidence interval (CI), 1.0-2.8 including rotenone (OR = 2.5; 95% CI, 1.3-4.7) and with use of a group of pesticides that cause oxidative stress (OR = 2.0; 95% CI, 1.2-3.6), including paraquat (OR = 2.5; 95% CI, 1.4-4.7). Conclusions: PD was positively associated with two groups of pesticides defined by mechanisms implicated experimentally—those that impair mitochondrial function and those that increase oxidative stress—supporting a role for these mechanisms in PD pathophysiology.
Objective:
Several case reports have linked solvent exposure to Parkinson disease (PD), but few studies have assessed associations with specific agents using an analytic epidemiologic design. We ...tested the hypothesis that exposure to specific solvents is associated with PD risk using a discordant twin pair design.
Methods:
Ninety‐nine twin pairs discordant for PD ascertained from the National Academy of Sciences/National Research Council World War II Veteran Twins Cohort were interviewed regarding lifetime occupations and hobbies using detailed job task–specific questionnaires. Exposures to 6 specific solvents selected a priori were estimated by expert raters unaware of case status.
Results:
Ever exposure to trichloroethylene (TCE) was associated with significantly increased risk of PD (odds ratio OR, 6.1; 95% confidence interval CI 1.2–33; p = 0.034), and exposure to perchloroethylene (PERC) and carbon tetrachloride (CCl4) tended toward significance (respectively: OR, 10.5; 95% CI, 0.97–113; p = 0.053; OR, 2.3; 95% CI, 0.9–6.1; p = 0.088). Results were similar for estimates of exposure duration and cumulative lifetime exposure.
Interpretation:
Exposure to specific solvents may increase risk of PD. TCE is the most common organic contaminant in groundwater, and PERC and CCl4 are also ubiquitous in the environment. Our findings require replication in other populations with well‐characterized exposures, but the potential public health implications are substantial. ANN NEUROL 2011
Abstract
Study Objectives
To evaluate the utility of multimodal low-cost approaches including actigraphy, a wrist-worn device monitoring rest/activity cycles, in identifying patients with idiopathic ...REM sleep behavior disorder (iRBD).
Methods
Seventy patients diagnosed with sleep disorders causing different motor manifestations during sleep (iRBD, sleep apnea, restless legs syndrome) and 20 subjects without any relevant motor manifestation during sleep, underwent video-polysomnography (vPSG) and 2 week actigraphy, completed six validated RBD screening questionnaires, and sleep apps use was assessed. Actigraphy was analyzed automatically, and visually by seven blinded sleep medicine experts who rated as “no,” “possible,” and “probable” RBD.
Results
Quantitative actigraphy analysis distinguished patients from controls, but not between patients with different types of motor activity during sleep. Visual actigraphy rating by blinded experts in sleep medicine using pattern recognition identified vPSG confirmed iRBD with 85%–95% sensitivity, 79%–91% specificity, 81%–91% accuracy, 57.7% ± 11.3% positive predictive value, 95.1% ± 3.3% negative predictive value, 6.8 ± 2.2 positive likelihood ratio, 0.14 ± 0.05 negative likelihood ratio and 0.874–0.933 area under the ROC curve (AUC). AUC of the best performing questionnaire was 0.868. Few patients used sleep apps; therefore, their potential utility in the evaluated patients’ groups is limited.
Conclusions
Visual analysis of actigraphy using pattern recognition can identify subjects with iRBD, and is able to distinguish iRBD from other motor activities during sleep, even when patients are not aware of the disease in contrast to questionnaires. Therefore, actigraphy can be a reliable screening instrument for RBD potentially useful in the general population.
Language and action systems are functionally coupled in the brain as demonstrated by converging evidence using Functional magnetic resonance imaging (fMRI), electroencephalography (EEG), transcranial ...magnetic stimulation (TMS), and lesion studies. In particular, this coupling has been demonstrated using the action-sentence compatibility effect (ACE) in which motor activity and language interact. The ACE task requires participants to listen to sentences that described actions typically performed with an open hand (e.g., clapping), a closed hand (e.g., hammering), or without any hand action (neutral); and to press a large button with either an open hand position or closed hand position immediately upon comprehending each sentence. The ACE is defined as a longer reaction time (RT) in the action-sentence incompatible conditions than in the compatible conditions. Here we investigated direct motor-language coupling in two novel and uniquely informative ways. First, we measured the behavioural ACE in patients with motor impairment (early Parkinson’s disease – EPD), and second, in epileptic patients with direct electrocorticography (ECoG) recordings. In experiment 1, EPD participants with preserved general cognitive repertoire, showed a much diminished ACE relative to non-EPD volunteers. Moreover, a correlation between ACE performance and action-verb processing (kissing and dancing test – KDT) was observed. Direct cortical recordings (ECoG) in motor and language areas (experiment 2) demonstrated simultaneous bidirectional effects: motor preparation affected language processing (N400 at left inferior frontal gyrus and middle/superior temporal gyrus), and language processing affected activity in movement-related areas (motor potential at premotor and M1). Our findings show that the ACE paradigm requires ongoing integration of preserved motor and language coupling (abolished in EPD) and engages motor-temporal cortices in a bidirectional way. In addition, both experiments suggest the presence of a motor-language network which is not restricted to somatotopically defined brain areas. These results open new pathways in the fields of motor diseases, theoretical approaches to language understanding, and models of action-perception coupling.
The relationship between Health-Related Quality of Life (HRQoL) and MDS-UPDRS has not been fully studied so far. The aim of this study was to evaluate the relationship between all MDS-UPDRS ...components and HRQoL in a representative international cohort of PD patients.
We collected demographic and disease-related data as well as MDS-UPDRS and PDQ8 scales. Data were analyzed using correlations between PDQ8 and all MDS-UPDRS items, subsequently two hierarchical multiple regressions were performed, first between the scores of the MDS-UPDRS Parts and PDQ8 and second between individual items from those Parts demonstrating significant relationship to PDQ8 scores in the first regression. LASSO regression analyses were performed to evaluate the relationship between PDQ8 and all individual MDS-UPDRS items.
A total of 3206 PD patients were included in the study. In the first regression analysis, PDQ8 was significantly related to MDS-UPDRS parts I and II, but not to III and IV. In the second regression model, significant contributions to PDQ8 were found for Part I items Fatigue, Pain, Depressed mood, Apathy; and Part II items Dressing, Doing hobbies, Freezing, Speech and Tremor. In the LASSO analysis, six Part I, seven Part II, three Part III and one Part IV items contributed to PDQ8 scores. The five items most significantly related to the model were Depressed mood, Dressing, Apathy, Pain and Fatigue.
This is so far the largest study related to HRQoL issues in PD. Restrictions in activities of daily living and non-motor symptoms significantly contribute to HRQoL in PD.
•This is the largest study related to Quality of Life (QoL) in PD so far.•QoL is related especially to MDS-UPDRS Part II (ADLs) and Part I (NMS).•Four out of five most important independent contributors were non-motor items.
Theory of mind (ToM) refers to the ability to infer others' mental states, including intentions and feelings, and is considered to be a critical part of social cognition. Earlier studies in ...individuals with Parkinson disease (PD) have shown ToM deficits in the more advanced stages of the disease. There is currently no evidence of social cognition deficits in patients in the early stages of PD.
In this study, we compared patients with early PD (n=36) and a control group of healthy subjects (n=36). Patients were assessed with 2 ToM tasks designed to differentially detect subtle deficits in the affective and cognitive aspects of ToM. Patients were also assessed with a complete neuropsychologic battery which included classic executive tests aimed at investigating the relationship between ToM and executive functions. Performance of medicated (n=16) and unmedicated (n=20) patients was also compared.
Our results are the first to indicate that ToM is affected in the early stages of PD. As has already been reported in more advanced stages of PD, such deficits seem to be related to the cognitive aspects of this domain. In our study, these deficits were not related with performance on executive functioning, depression, or medication usage.
These results provide evidence for ToM impairments early in the course of PD. Recognition of ToM impairments in early PD is important, as these deficits may impact patients' social interactions and quality of life.
The phonological verbal fluency test can act as a fast screening test to detect cognitive deficits in neurological conditions. In the present study, its utility in the detection of executive deficits ...in patients with early Parkinson's disease is demonstrated.
In Response To:
Frucht SJ. Focal task-specific dystonia—from early descriptions to a
new, modern formulation. Tremor Other Hyperkinet Mov. 2014; 4. doi:
10.7916/D8VD6WHP
Background. A “dysexecutive” group of patients with Alzheimer disease (AD) has been previously identified, and these patients have been found to present higher frequency of psychiatric symptoms and ...more pronounced functional impact. This study aimed at evaluating the frequency of neuropsychiatric symptoms in patients with early AD who present with impaired executive functioning. Methods. Thirty patients with early AD diagnosis were divided into a spared (SEF) and an impaired (IEF) executive functioning group according to their performance scores on neuropsychological tests. Their closest relatives or caregivers completed the Cambridge behavioral inventory (CBI), which assesses behavioral symptoms grouped into 13 categories. Results. A significant difference was exclusively found between SEF and IEF in terms of the frequency of stereotypies and repetitive motor behavior (U=60.5, P=.024). Conclusions. The presence of stereotypies could be associated with a dysexecutive profile in AD patients. These results shed light on the role of frontal circuitry in the expression of motor symptoms in AD and prompt for further research that will contribute to the differential diagnosis both of different subtypes of AD and other types of dementia.
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