Association of Parkinson's Disease and Its Subtypes with Agricultural Pesticide Exposures in Men: A Case-Control Study in France.

BACKGROUND: Pesticides have been associated with Parkinson's disease (PD), but there are few data on important exposure characteristics such as dose-effect relations. It is unknown whether associations depend on clinical PD subtypes. OBJECTIVES: We examined quantitative aspects of occupational pesticide exposure associated with PD and investigated whether associations were similar across PD subtypes. METHODS: As part of a French population-based case-control study including men enrolled in the health insurance plan for farmers and agricultural workers, cases with clinically confirmed PD were identified through antiparkinsonian drug claims. Two controls were matched to each case. Using a comprehensive occupational questionnaire, we computed indicators for different dimensions of exposure (duration, cumulative exposure, intensity). We used conditional logistic regression to compute odds ratios (ORs) and 95% confidence intervals (CIs) among exposed male farmers (133 cases, 298 controls). We examined the relation between pesticides and PD subtypes (tremor dominant/non-tremor dominant) using polytomous logistic regression. RESULTS: There appeared to be a stronger association with intensity than duration of pesticide exposure based on separate models, as well as a synergistic interaction between duration and intensity (p-interaction = 0.04). High-intensity exposure to insecticides was positively associated with PD among those with low-intensity exposure to fungicides and vice versa, suggesting independent effects. Pesticide exposure in farms that specialized in vineyards was associated with PD (OR = 2.56; 95% CI: 1.31, 4.98). The association with intensity of pesticide use was stronger, although not significantly (p-heterogeneity = 0.60), for tremor-dominant (p-trend < 0.01) than for non-tremor-dominant PD (p-trend = 0.24). CONCLUSIONS: This study helps to better characterize different aspects of pesticide exposure associated with PD, and shows a significant association of pesticides with tremor-dominant PD in men, the most typical PD presentation. CITATION: Moisan F, Spinosi J, Delabre L, Gourlet V, Mazurie JL, Bénatru I, Goldberg M, Weisskopf MG, Imbernon E, Tzourio C, Elbaz A. 2015. Association of Parkinson's disease and its subtypes with agricultural pesticide exposures in men: a case-control study in France. Environ Health Perspect 123:1123-1129; http://dx.doi.org/10.1289/ehp.1307970.

Metabolic syndrome and disability: findings from the prospective three-city study.

BACKGROUND: Metabolic syndrome (MetS) is a potentially reversible cause of disability in the elderly people. The published literature suggests that the MetS-disability association is likely to be complex, depending on co-existing risk factors and with possible variation for each of the specific MetS components. Further evidence is needed to understand the specific consequences of the MetS as a whole and as a function of its components. METHODS: Prospective analyses included data from 6,141 participants (60.9% women) aged 65 and older from the Three-City cohort. Mixed logistic models were used to determine associations between MetS (National Cholesterol Education Program Adult Treatment Panel III criteria) and 7-year incident disability measured as social restriction, mobility limitations (Rosow and Breslau scale), and limitations in instrumental and basic activities of daily living. RESULTS: MetS was associated with incident social restriction (odds ratio = 1.55, 95% CI: 1.14-2.09), limited mobility (odds ratio = 1.52, 95% CI: 1.21-1.90), and instrumental activities of daily living limitations (odds ratio = 1.62, 95% CI: 1.24-2.10) after adjustment for a range of potential sociodemographic, health behavior, and health status confounders at baseline. These associations were independent of chronic conditions, including cardiovascular disease and dementia. There was evidence of associations between MetS components: central obesity, high triglycerides, and elevated fasting glucose and incidence of limitations in mobility and instrumental activities of daily living. CONCLUSIONS: Our results suggest that the increased risk of mobility and instrumental activities of daily living limitations in the elderly people associated with MetS is over and above that associated with its components.

FXTAS: new insights and the need for revised diagnostic criteria.

OBJECTIVE: Fragile X-associated tremor ataxia syndrome (FXTAS) is defined by FMR1 premutation, cerebellar ataxia, intentional tremor, and middle cerebellar peduncle (MCP) hyperintensities. We delineate the clinical, neurophysiologic, and morphologic characteristics of FXTAS. METHODS: Clinical, morphologic (brain MRI, (123)I-ioflupane SPECT), and neurophysiologic (tremor recording, nerve conduction studies) study in 22 patients with FXTAS, including 4 women. RESULTS: A total of 43% of patients had no family history of fragile X syndrome (FXS), which contrasts with previous FXTAS series. A total of 86% of patients had tremor and 81% peripheral neuropathy. We identified 3 electroclinical tremor patterns: essential-like (35%), cerebellar (29%), and parkinsonian (12%). Two electrophysiologic patterns evocative of non-length-dependent (56%) and length-dependent sensory neuropathy (25%) were identified. Corpus callosum splenium (CCS) hyperintensity was as frequent (68%) as MCP hyperintensities (64%). Sixty percent of patients had parkinsonism and 47% abnormal (123)I-ioflupane SPECT. Unified Parkinson's Disease Rating Scale motor score was correlated to abnormal (123)I-ioflupane SPECT (p = 0.02) and to CGG repeat number (p = 0.0004). Scale for the assessment and rating of ataxia correlated with dentate nuclei hyperintensities (p = 0.03) and CCS hyperintensity was a marker of severe disease progression (p = 0.04). CONCLUSIONS: We recommend to include in the FXTAS testing guidelines both CCS hyperintensity and peripheral neuropathy and to consider them as new major radiologic and minor clinical criterion, respectively, for the diagnosis of FXTAS. FXTAS should also be considered in women or when tremor, MCP hyperintensities, or family history of FXS are lacking. Our study broadens the spectrum of tremor, peripheral neuropathy, and MRI abnormalities in FXTAS, hence revealing the need for revised criteria.

Prediction model of Parkinson's disease based on antiparkinsonian drug claims.

Drug claims databases are increasingly available and provide opportunities to investigate epidemiologic questions. The authors used computerized drug claims databases from a social security system in 5 French districts to predict the probability that a person had Parkinson's disease (PD) based on patterns of antiparkinsonian drug (APD) use. Clinical information for a population-based sample of persons using APDs in 2007 was collected. The authors built a prediction model using demographic variables and APDs as predictors and investigated the additional predictive benefit of including information on dose and regularity of use. Among 1,114 APD users, 320 (29%) had PD and 794 (71%) had another diagnosis as determined by study neurologists. A logistic model including information on cumulative APD dose and regularity of use showed good performance (c statistic = 0.953, sensitivity = 92.5%, specificity = 86.4%). Predicted PD prevalence (among persons aged ≥18 years) was 6.66/1,000; correcting this estimate using sensitivity/specificity led to a similar figure (6.04/1,000). These data demonstrate that drug claims databases can be used to estimate the probability that a person is being treated for PD and that information on APD dose and regularity of use improves models' performances. Similar approaches could be developed for other conditions.

Olive oil and cognition: results from the three-city study.

BACKGROUND: Olive oil is a major component of the Mediterranean diet suggested to be beneficial to counteract Alzheimer's disease. AIM OF THE STUDY: Our objective was to examine the association between olive oil use, cognitive deficit and cognitive decline in a large elderly population. METHODS: We followed 6,947 subjects with a brief baseline food frequency questionnaire and repeated cognitive tests. Olive oil intake was categorized as none (22.7%), moderate (use for cooking or dressing, 39.9%) and intensive (use for both cooking and dressing, 37.4%). Associations between olive oil and cognitive outcomes were examined taking into account socio-economic factors, health behaviors, health measures and other dietary intakes. RESULTS: Participants with moderate or intensive use of olive oil compared to those who never used olive oil showed lower odds of cognitive deficit for verbal fluency and visual memory. For cognitive decline during the 4-year follow-up, the association with intensive use was significant for visual memory (adjusted OR = 0.83, 95% CI: 0.69-0.99) but not for verbal fluency (OR = 0.85, 95% CI: 0.70-1.03) in multivariate analysis. CONCLUSIONS: This olive oil-cognition association needs to be confirmed by further studies. However, our findings already shed light on the potential importance of olive oil in the Mediterranean diet and on its beneficial effects on health.

Changes in blood pressure in a large cohort of elderly individuals: Study 3C.

OBJECTIVE: Analysis of changes in blood pressure with a two-year interval, and of factors associated with this change, in a large cohort of elderly individuals. METHODS: Follow-up of a cohort of 9294 individuals aged 65 years and over recruited from the general population for Study 3C. Changes in blood pressure are defined as the difference in its averages between the inclusion visit and the follow-up visit at 2 years. The factors associated with changes in systolic blood pressure were identified by univariate and multivariate analyses. RESULTS: Systolic and diastolic blood pressure decreased on average by 7.60 mmHg and 4.45 mmHg respectively in 7659 individuals included in the study between the initial measurement and the follow-up at 2 years. The analyses revealed that the initial high blood pressure level was the main factor for this decrease that would be explained by a phenomenon of regression towards the mean. CONCLUSION: These results confirm the importance of repeating blood pressure measurements during several examinations for a good estimate of individual blood pressure values in this age range. It is also important to consider this phenomenon in studies including specific blood pressure estimates only.

Plasma carotenoid levels and cognitive performance in an elderly population: results of the EVA Study.

BACKGROUND: The hypothesis of carotenoids having a preventive role in cognitive impairment is suggested by their antioxidant properties. METHODS: We examined, in a cross-sectional analysis, the relationship between cognitive performance (assessed by the Mini-Mental State Examination, Trail Making Test Part B, Digit Symbol Substitution, Finger Tapping Test, and Word Fluency Test) and different plasma carotenoids (lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, and trans-beta-carotene and cis-beta-carotene) in a healthy elderly population (the EVA,"Etude du Vieillissement Artériel," study; n = 589, age = 73.5 +/- 3 years). RESULTS: Logistic regression showed that participants with the lowest cognitive functioning (<25th percentile) had a higher probability of having low levels of specific plasma carotenoids (<1st quartile): lycopene and zeaxanthin. For zeaxanthin, odds ratios (ORs) were as follows: OR(DSS) = 1.97 (95% confidence interval [CI] = 1.21-3.20), OR(FTT) = 1.70 (CI = 1.05-2.74), and OR(WFT) = 1.82 (CI = 1.08-3.07); for lycopene, OR(DSS) = 1.93 (CI = 1.20-3.12) and OR(TMTB) = 1.64 (CI = 1.04-2.59). CONCLUSION: Even if it is not possible to affirm if these low levels of carotenoids precede or are the consequence of cognitive impairment, our results suggest that low carotenoid levels could play a role in cognitive impairment. The biological significance of our findings needs further research.

Plasma selenium over time and cognitive decline in the elderly.

BACKGROUND: Because brain oxidative stress is a cause of cognitive impairment, selenium, which is an antioxidant, may protect against cognitive decline. The aim of the study was to examine whether declining selenium levels over time are associated with cognitive decline in a cohort of community-dwelling French elderly. METHODS: During 1991-1993, 1389 subjects (age 60-71 years) were recruited into a 9-year longitudinal study with 6 waves of follow-up. Cognitive functions were evaluated by neuropsychologic tests. To take into account the entire set of cognitive measurements and the within-subject correlations between measures, we analyzed mixed linear and logistic models to study associations between selenium change and cognitive decline. RESULTS: After controlling for potential confounders, cognitive decline was associated with decreases of plasma selenium over time. Among subjects who had a decrease in their plasma selenium levels, the greater the decrease in plasma selenium, the higher the probability of cognitive decline. Among subjects who had an increase in their plasma selenium levels, cognitive decline was greater in subjects with the smallest selenium increase. There was no association between short-term (2-year) selenium change and cognitive changes. CONCLUSION: Selenium status decreases with age and may contribute to declines in neuropsychologic functions among aging people.

Selenium and mortality in the elderly: results from the EVA study.

BACKGROUND: Inadequate plasma selenium can adversely affect the maintenance of optimal health; therefore, reported decreases in plasma selenium in an aging population are cause for concern. To further examine this hypothesis, we explored the relationships between plasma selenium and mortality in an elderly population: the EVA (Etude du Vieillissement Artériel) study. METHODS: The EVA study was a 9-year longitudinal study with 6 periods of follow-up. During the 2-year period from 1991 to 1993 (EVA0), 1389 men and women born between 1922 and 1932 were recruited. The effects of plasma selenium at baseline on mortality were determined by Cox proportional hazards regression analysis, adjusting for the following variables: sociodemographic characteristics, dietary habits, health, and cognitive factors. RESULTS: During the 9-year follow-up, 101 study participants died. Baseline plasma selenium was higher in individuals who were alive at the end of follow-up [mean (SD), 1.10 (0.20) micromol/L] than in those who died during the follow-up [1.01 (0.20) micromol/L; P <10(-4)]. Mortality rates were significantly higher in individuals with low selenium [increments = 0.2 micromol/L; relative risk (RR) = 1.56 (95% confidence interval, 1.28-1.89)]. After we controlled for various potential confounding factors, this association remained significant [RR = 1.54 (1.25-1.88)]. When the underlying causes of death were considered, we found an association with cancer-related mortality [adjusted RR = 1.79 (1.32-2.44)]. CONCLUSIONS: Even if it is premature to present selenium as a longevity indicator in an elderly population, our results are in accordance those of large, interventional, randomized trials with selenium, which suggest that this essential trace element plays a role in health maintenance in aging individuals.

Enzymatic antioxidant balance and cognitive decline in aging--the EVA study.

We studied whether primary enzymatic antioxidant protection should influence cognitive decline (CD) in subjects aged 62-72 years volunteers in the Etude du Vieillissement Antériel (EVA) cohort. At baseline, we measured red blood cells activities of two enzymes: cytoplasmic form of superoxide dismutase (CuZn-SOD) and seleno dependent glutathione peroxidase (GSH-Px). During the 4 year-follow up (follow-up rate of 81%), a drop of at least 3 points in MMSE score was observed in 71 subjects (7.2%) defining individuals with CD+ among the 980 individuals. Initial GSH-Px activity appeared to be significantly lower in individual CD+ (41.2 +/- 10.3 U/g Hb vs. 44.4 +/- 9.4 in CD-, p = 0.008). Conversely, there was an increase of CuZn-SOD activity in CD+ subjects (1.13 +/- 0.10 U/mg Hb vs. 1.10 +/- 0.10, p = 0.05). Taking into account the ratio between these two levels suggest that the equilibrium between these two enzymes, an important determinant of oxidative stress level, is associated with CD. These results are independent of other potential risk factors for CD (education, Apolipoprotein E, hypertension) and suggest that this primary enzymatic system could be related to CD during aging.

Hormone replacement therapy use is associated with a lower occurrence of carotid atherosclerotic plaques but not with intima-media thickness progression among postmenopausal women. The vascular aging (EVA) study.

BACKGROUND: Information on the impact of hormone replacement therapy (HRT) on carotid atherosclerosis is limited. Moreover, transdermal estrogens have not been investigated. METHODS: We examined association of HRT use with ultrasonographically assessed carotid atherosclerotic plaque occurrence and mean common carotid artery intima-media thickness (CCA-IMT) progression. Within the Vascular Aging (EVA) Study, a community-based cohort, 815 postmenopausal women aged 59-71 have been followed during 4 years. Among these women, 166 had already used HRT. RESULTS: Women who had ever used HRT experienced a lower occurrence of plaques (8.6 versus 19.1%, P=0.003). After adjustment for the main cardiovascular risk factors, odds-ratio for plaque occurrence was 0.41 (95% confidence interval 0.21-0.78, P=0.01) among ever users of HRT compared with never users. When transdermal route of estrogen administration was used, adjusted odds-ratio was 0.66 (95% confidence interval 0.47-0.99, P=0.04). The progression of IMT, which was measured at a plaque-free site and adjusted on initial levels of CCA-IMT did not differ between ever and never users of HRT. It was 0.011 mm per year among ever users and 0.012 mm per year among never users (P=0.61). CONCLUSION: These data suggest that HRT use may prevent the development of atherosclerotic plaques in postmenopausal women, especially when estrogens are administered by transdermal route.