Human Predisposition to Cognitive Impairment and Its Relation with Environmental Exposure to Potentially Toxic Elements
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Environ Geochem Health DOI 10.1007/s10653-017-9928-3 ORIGINAL PAPER Human predisposition to cognitive impairment and its relation with environmental exposure to potentially toxic elements Marina M. S. Cabral Pinto . A. Paula Marinho-Reis . Agostinho Almeida . Carlos M. Ordens . Maria M. V. G. Silva . Sandra Freitas . Ma´rio R. Simo˜es . Paula I. Moreira . Pedro A. Dinis . M. Luı´sa Diniz . Eduardo A. Ferreira da Silva . M. Teresa Condesso de Melo Received: 24 May 2016 / Accepted: 27 February 2017 Ó Springer Science+Business Media Dordrecht 2017 Abstract New lines of evidence suggest that less neuropsychological assessment carried out in elderly than 10% of neurodegenerative diseases have a strict residents of the industrial city of Estarreja. A battery of genetic aetiology and other factors may be prevalent. cognitive tests and a personal questionnaire were Environmental exposures to potentially toxic elements administered to the participants. Multivariate analysis appear to be a risk factor for Parkinson’s, Alzheimer’s and multiple linear regression analysis were used to and sclerosis diseases. This study proposes a multi- identify potential relationships between the cognitive disciplinary approach combining neurosciences, psy- status of the participants and environmental exposure chology and environmental sciences while integrating to potentially toxic elements. The results suggest a socio-economic, neuropsychological, environmental relationship between urinary PTEs levels and the and health data. We present the preliminary results of a incidence of cognitive disorders. They also point towards water consumption habits and profession as relevant factors of exposure. Linear regression models Electronic supplementary material The online version of 2 this article (doi:10.1007/s10653-017-9928-3) contains supple- show that aluminium (R = 38%), cadmium mentary material, which is available to authorized users. M. M. S. Cabral Pinto Á A. P. Marinho-Reis Á C. M. Ordens M. L. Diniz Á E. A. Ferreira da Silva University College London Australia, Adelaide, Department of Geosciences, Geobiotec Research Centre, South Australia 5000, Australia University of Aveiro, 3810-193 Aveiro, Portugal M. M. V. G. Silva M. M. S. Cabral Pinto Á S. Freitas Á P. I. Moreira CEMUC, University of Coimbra, 3030-790 Coimbra, CNC-Center for Neuroscience and Cell Biology, Faculty Portugal of Medicine, University of Coimbra, 3030-548 Coimbra, Portugal S. Freitas Á M. R. Simo˜es Centro de Investigac¸a˜odoNu´cleo de Estudos e M. M. S. Cabral Pinto (&) Á M. M. V. G. Silva Á Intervenc¸a˜o Cognitivo Comportamental (CINEICC), P. A. Dinis Universidade de Coimbra, Coimbra, Portugal Department of Earth Sciences, University of Coimbra, 3030-790 Coimbra, Portugal M. R. Simo˜es e-mail: [email protected] Faculdade de Psicologia e de Cieˆncias da Educac¸a˜oda Universidade de Coimbra (FPCE-UC), Coimbra, Portugal A. Almeida LAQV/REQUIMTE, Department of Chemical Sciences, P. I. Moreira Laboratory of Applied Chemistry, Faculty of Pharmacy, Laboratory of Physiology, Faculty of Medicine, Porto University, 4050-313 Porto, Portugal University of Coimbra, 3000-548 Coimbra, Portugal 123 Environ Geochem Health (R2 = 11%) and zinc (R2 = 6%) are good predictors origin (Monnet-Tschudi et al. 2006; Kozlowski et al. of the scores of the Mini-Mental State Examination 2009; Johnson and Atchison 2009; Chin-Chan et al. cognitive test. Median contents (lg/l) in groundwater 2015; Tartaglione et al. 2015). A gene–environmental are above admissible levels for drinking water for interaction provides a plausible explanation for the aluminium (371), iron (860), manganese (250), and other *90% of cases (Johnson and Atchison 2009). zinc (305). While the World Health Organization does Occupational and environmental (chronic) exposure to not provide health-based reference values for alu- specific PTEs (manganese [Mn], copper [Cu], lead minium, results obtained from this study suggest that it [Pb], iron [Fe], mercury [Hg], zinc [Zn], aluminium may have an important role in the cognitive status of [Al], cadmium [Cd]) has been suggested as a possible the elderly. Urine proved to be a suitable biomarker of cause of neurodegenerative disorders, such as man- exposure both to elements with low and high excretion ganism, Parkinson’s disease (PD), Alzheimer’s dis- rates. ease (AD) and sclerosis (Gorell et al. 1999; Cerpa et al. 2005; Gupta et al. 2005; Maynard et al. 2005; Moreira Keywords Neurodegenerative diseases Á et al. 2005, 2006; Bocca et al. 2006; Yokel 2006; Environmental exposure Á Potentially toxic elements Á Bressler et al. 2007; Fabrizio et al. 2007; Kozlowski Urine Á Groundwater et al. 2009; Johnson and Atchison 2009; Exley 2012; Exley and House 2012; Ferrer 2012; Cabral Pinto et al. Introduction 2013, 2015; Forte et al. 2014; Ashok et al. 2015; Ahlskog 2016). Soil and water are the vehicles which link the Alzheimer’s disease is the most common condition inorganic environment to life by supplying the essen- of dementia among the elderly. However, it is tial macro- and micronutrients to living organisms, important noting that dementia is not an inevitable con- and particularly to humans. Variations in the chemical sequence of ageing but often has a concealed cause composition of soil and water cause metabolic (Ferrer 2012). The development of other neurodegen- changes, favouring the occurrence of endemic dis- erative diseases, such as PD or amyotrophic lateral eases, related to either deficient or excessive intake, sclerosis (ALS), is also accompanied by cognitive such as gout, fluorosis and Keshan’s disease or decline, like mild cognitive impairment (MCI) and arsenicosis (Komatina 2004). Until the last decade, several dementia levels (Lemos et al. 2014), at the little attention was given from the neuroscience level of global cognitive status and cognitive domains. community to the neurometabolism of potentially Currently, epidemiological studies often use urine, toxic elements (Zatta et al. 2003). However, the hair, and toenail as biological material of exposure neurobiology of the potentially toxic elements (PTEs) because they are less invasive and the samples are easy is now receiving growing interest, since it has been to obtain in large populations (Reis et al. 2015). The linked to major neurodegenerative diseases (Zatta information provided by each biological matrix is et al. 2003; Forte et al. 2004; Gupta et al. 2005; Bocca rather different. Urine generally reflects recent expo- et al. 2006; Gomes and Wittung-Stafshede 2010; sures (days/few weeks), and hair and nails reflect Hozumi et al. 2011; Exley and House 2012; Zhang exposures occurring in the last weeks/months (Coelho et al. 2013; Ashok et al. 2015; Chin-Chan et al. 2015; et al. 2012). However, this distinction is not straight- Ahlskog 2016; Tartaglione et al. 2015). forward for some elements. The half-life, which Recent research has been suggesting that no more characterizes the elimination of metals from the body, than 10% of neurological diseases have a strict genetic varies widely between PTEs. It can be larger than aetiology, while the majority of cases have unknown 10–12 years for Cd and Pb, with inter-individual variability of about 30%, 4 days for arsenic (As), P. A. Dinis 60 days for Hg and 0.5–1 year for uranium (Dorne MARE - Marine and Environmental Sciences Centre, et al. 2011) and Zn (Nriagu 2007). Hence, concentra- University of Coimbra, 3030-790 Coimbra, Portugal tions of different PTEs in urine may provide valuable information on exposure within different time spans, M. T. Condesso de Melo CEris, DECivil, Instituto Superior Te´cnico, Universidade thus helping to better assess the health effects. Most de Lisboa, Lisbon, Portugal PTEs are excreted via the kidney in the urine and to a 123 Environ Geochem Health much lesser extent by the gastrointestinal tract (Dorne and comparing with maximum permissible levels et al. 2011). established in the Portuguese guidelines; and (v) ascer- Since increasing lines of evidence suggest that taining the efficacy of the selected biomarker to environmental exposures may be prevalent in the provide complementary information on environmental development of neurodegenerative disorders, studying exposure to PTEs. the impact of exposure to environmental PTEs such as Mn, Cu, Pb, Fe, Hg, Zn, Al, Cd, As on the cognitive functioning of elderly people requires further atten- Study area tion. Hence, we propose a multidisciplinary research that combines the areas of neurosciences, psychology Estarreja is a municipality within the Aveiro District and environmental sciences.. (central Portugal) with 26,997 inhabitants (INE 2012). The Estarreja Chemical Complex (ECC), located in The city of Estarreja is located in a low-altitude Estarreja, central Portugal, has an intense industrial (10–70 m), gentle slope (\2%) area that comprises activity with negative impacts on air, soil, sediment, several wetlands and shows intense agriculture, fish- surface water and groundwater since the early 1950s, eries and industrial activities (Fig. 1a–c). while having a population that historically relies on The geology is characterized by the predominance groundwater as a source of water supply for human, of Quaternary unconsolidated sands and clays depos- cattle and agricultural uses. Surface and groundwater, ited in dune, beach and lagoon environments (Fig. 1b). soil and sediment contamination has been extensively These sedimentary units dip gently to the west and reported for the Estarreja region (Leita˜o 1996; Pereira cover Proterozoic metamorphic rocks and Mesozoic et al. 2009; Van der Weijden and Pacheco 2006; siliciclastic formations (Teixeira and Assunc¸a˜o 1963). Ordens 2007; Ina´cio et al. 2014). Such contamination The principal watercourse crossing the city of Estar- has been linked to the industrial activities, enhanced reja is the Antua˜ River, a tributary of the Vouga River by a natural vulnerability to contamination due to a (Fig. 1). combination of factors such as high permeability of The ECC is located close to the city and has been the sandy soils, shallow aquifers, flat topography and working since the thirties of the twentieth century, high rates of groundwater recharge (Ordens 2007).