Pesticide exposure and cognitive function: Results from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD)
Introduction
Alzheimer's Disease (AD) is a neurodegenerative disorder with an irreversible and progressive course (Wang et al., 2017), constituting the main cause of dementia (Scheltens et al., 2016). Approximately 40 million people have dementia worldwide, a number which is thought to be doubling every two decades (Prince et al., 2013). Among European citizens over the age of 65 years, the prevalence of AD is estimated to be around 5% (Niu et al., 2017).
The pathophysiology of dementia remains largely unknown (Elahi and Miller, 2017). However, there is evidence to suggest that genetic factors could explain a high proportion of dementia cases (Cuyvers and Sleegers, 2016; Loy et al., 2014). Moreover, environmental factors, including smoking (Zhong et al., 2015), obesity (Singh-Manoux et al., 2018), pesticide exposure (Killin et al., 2016), alongside the effect of epigenetic mechanisms (Maloney and Lahiri, 2016), as a potential connecting link between genetic and environmental factors, may also constitute modifiable causes of the development and course of dementia.
Several studies have examined the contribution of chronic pesticide exposure to the risk of dementia and AD. More specifically, increased risk of AD due to occupational exposure to pesticides was originally reported in the Canadian Study of Health and Aging (1994). Afterwards, it was shown that in occupationally exposed people, cognitive impairment appears to persist even after retirement from work (Baldi et al., 2003), and that the risk of AD and dementia may be increased in later life (Hayden et al., 2010). Accordingly, environmental pesticide exposure, in areas with a high level of pesticide use, was associated with AD and a few other neurodegenerative and psychiatric disorders as well (Parron et al., 2011). More recently, a study in Chile (Corral et al., 2017) has shown that even indirect exposure to pesticides, referring to people who never used pesticides but who lived in areas environmentally exposed to chronic use of pesticides, affects cognitive functioning. In a recent systematic review, pesticide exposure was even characterized as a moderate putative risk factor of dementia (Killin et al., 2016), and an additional positive association between pesticide exposure and AD was suggested in a recent meta-analysis (Yan et al., 2016), confirming that pesticide exposure might indeed be a risk factor for AD.
Pesticide exposure has also been associated with mild cognitive impairment (MCI) (Bosma et al., 2000), as well as vascular dementia (VD) and PD-dementia, but not frontotemporal lobar degeneration (FTLD) (Zaganas et al., 2013). In addition, different aspects of cognitive performance (selective attention, symbol-digit, Mini-Mental State Examination score, reaction time tests) seem to be adversely influenced by pesticide exposure (Baldi et al., 2011; Rohlman et al., 2007; Zaganas et al., 2013).
Nevertheless, other studies have revealed a weak or no evident association between AD and pesticide exposure (French et al., 1985; Gauthier et al., 2001; Gun et al., 1997; Povey et al., 2014; Tyas et al., 2001). Interestingly, pesticide exposure was negatively associated with non-vascular dementia among men, in a prospective Dutch cohort study (Koeman et al., 2015).
Overall, findings from studies regarding the role of pesticides in cognitive performance and dementia remain contradictory. One of the methodological limitations in the current literature includes the focus on specific neuropsychological tests, or specific phenotypes, without covering a broad range of cognitive performance as expressed with measurements of major cognitive domains. Furthermore, there is limited data and awareness regarding the actual exposure of the Greek population to pesticides (Dardiotis et al., 2014; Tsolaki et al., 1999). Our group recently explored the frequency, types and attitudes towards the use of pesticides (Moza et al., 2019). In the present article, we present the results from an analysis regarding self-reported pesticide exposure in a Greek cohort, based on an ongoing epidemiological study the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) (Anastasiou et al., 2017; Dardiotis et al., 2014; Kosmidis et al., 2018; Ntanasi et al., 2018a, 2018b; Tsapanou et al., 2017a, 2017b).
Section snippets
Study population
Details regarding the study design have been extensively described previously (Anastasiou et al., 2017; Dardiotis et al., 2014; Kosmidis et al., 2018; Ntanasi et al., 2018a; Tsapanou et al., 2017a, 2017b). In brief, the participants’ recruitment began in 2011, for baseline assessment, and a three-year follow-up, is currently being conducted.
Participants were selected based on random sampling among a municipal roster of individuals over the age of 64 years. No weighting or further stratification
Main results
From eligible participants (excluding those who had incomplete data, who had relocated, could not actively be recruited, died or were not contacted yet from the initial sample), 56.4% agreed to participate in HELIAD. To date, a total of 1462 Thessaly inhabitants have completed the detailed risk factor questionnaires. A cohort of 1397 non-demented (1218 cognitively healthy individuals and 179 individuals with MCI) individuals was included in the present analyses.
Comparisons of participant
Discussion
In the present study, we evaluated a relatively large number of individuals and examined the relationship between the level of self-reported pesticide exposure and cognitive function. We found that non-demented individuals who reported that they had been living in areas near sprayed fields, had lower cognitive performance, compared to those who had never lived in such areas. Specifically, they had poorer performance in executive functioning, visuospatial perception, language and attention
Declaration of interest
Efthimios Dardiotis, Vasileios Siokas, Sotiria Moza, Mary H. Kosmidis, Christina Vogiatzi, Athina-Maria Aloizou, Nikoletta Geronikola, Eva Ntanasi, Ioannis Zalonis, Mary Yannakoulia, and Georgios M. Hadjigeorgiou declare that they have no conflict of interest. Nikolaos Scarmeas reports personal fees from Merck Consumer Health and personal fees from NIH unrelated to this manuscript.
Funding
This study was supported by the following grants:IIRG-09- 133014 from the Alzheimer's Association; 189 10276/8/9/2011 from the ESPA-EU program Excellence Grant (ARISTEIA), which is co-funded by the European Social Fund and Greek National resources, and ΔΥ2β/οικ.51657/14.4.2009 from the Ministry for Health and Social Solidarity (Greece).
References (63)
Pesticide exposure and risk of mild cognitive dysfunction
Lancet
(2000)Cognitive impairment in agricultural workers and nearby residents exposed to pesticides in the Coquimbo Region of Chile
Neurotoxicol. Teratol.
(2017)- et al.
Genetic variations underlying Alzheimer's disease: evidence from genome-wide association studies and beyond
Lancet Neurol.
(2016) The interplay between environmental and genetic factors in Parkinson's disease susceptibility: the evidence for pesticides
Toxicology
(2013)Genetic polymorphisms in amyotrophic lateral sclerosis: evidence for implication in detoxification pathways of environmental toxicants
Environ. Int.
(2018)Mini-mental state". A practical method for grading the cognitive state of patients for the clinician
J. Psychiatr. Res.
(1975)- et al.
Pesticide exposure and Parkinson's disease: epidemiological evidence of association
Neurotoxicology (Little Rock)
(2012) Environmental pesticide exposure as a risk factor for Alzheimer's disease: a case-control study
Environ. Res.
(2001)Development, reliability and validity of a physical activity questionnaire for estimating energy expenditure in Greek adults
Sci. Sport.
(2016)Genetics of dementia
Lancet
(2014)
Epigenetics of dementia: understanding the disease as a transformation rather than a state
Lancet Neurol.
Prevalence and incidence of Alzheimer's disease in Europe: a meta-analysis
Neurologia
Association between environmental exposure to pesticides and neurodegenerative diseases
Toxicol. Appl. Pharmacol.
Pesticide exposure and screen-positive neuropsychiatric disease in British sheep farmers
Environ. Res.
Neurobehavioral performance of adult and adolescent agricultural workers
Neurotoxicology (Little Rock)
Alzheimer's disease
Lancet
Obesity trajectories and risk of dementia: 28 years of follow-up in the Whitehall II Study
Alzheimers Dement
Sleep quality and duration in relation to memory in the elderly: initial results from the Hellenic longitudinal investigation of aging and diet
Neurobiol. Learn. Mem.
Dataset on the associations between sleep quality/duration and cognitive performance in cognitively healthy older adults
Data Brief
Pesticide levels in head hair samples of Cretan population as an indicator of present and past exposure
Forensic Sci. Int.
Linking pesticide exposure and dementia: what is the evidence?
Toxicology
Diagnostic and Statistical Manual of Mental Disorders
Mediterranean diet and cognitive health: initial results from the Hellenic longitudinal investigation of ageing and Diet
PLoS One
Neurodegenerative diseases and exposure to pesticides in the elderly
Am. J. Epidemiol.
Neurobehavioral effects of long-term exposure to pesticides: results from the 4-year follow-up of the PHYTONER study
Occup. Environ. Med.
Contributions to Neuropsychological Assessment: a Clinical Manual
Higher probability of prodromal Parkinson disease is related to lower cognitive performance
Neurology
Do age and education contribute to performance on the clock drawing test? Normative data for the Greek population
J. Clin. Exp. Neuropsychol.
Patterns of cognitive decline prior to dementia in persons with mild cognitive impairment
J. Alzheimer's Dis.
The Hellenic Longitudinal Investigation of Aging and Diet (HELIAD): rationale, study design, and cohort description
Neuroepidemiology
A clinicopathological approach to the diagnosis of dementia
Nat. Rev. Neurol.
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