15 August 2019
Does low-level exposure to lead and manganese affect cognition and behaviour?
The Salud Ambiental Montevideo cohort is characterised by several social-environmental factors, including exposure to metals and cognitive performance. We caught up with Seth Frndak from the University of Buffalo to talk through CANTAB’s role in this epidemiological study.
Can you tell us more about yourself?
I am a PhD student in the Epidemiology and Environmental Health Department at the University at Buffalo. My research looks at the socio-environmental context within which children grow. I find cognitive outcomes especially fascinating because they allow me to cross disciplinary boundaries: I have become a student of psychology, sociology, genetics, nutrition, and toxicology (to name a few). I hope that the knowledge gained through my research will contribute to a better future for children by creating healthy communities and rich environments for learning and growth.
Which cohort are you working with?
Salud Ambiental Montevideo (SAM) means Environmental Health Montevideo. Since 2009, SAM has recruited Uruguayan first-graders and their families residing in Montevideo. Children enrolled in SAM have been characterized in terms of their exposure to metals, pesticides, diet and nutritional status, family characteristics, and cognitive performance. SAM’s primary goal is to elucidate how low-level exposure to toxins affects child cognition and behaviour.
What is your research question?
Lead is a neurotoxin affecting child cognition even at low levels of exposure. Despite years of research, it is not well understood if paediatric lead exposure produces a specific behavioural signature. Stiles and Bellinger (1993) tested, but did not find a behavioural signature of lead. However, they suggested that executive functions and attention may be disproportionally affected by lead exposure. With 70% of our sample had a blood lead level below 5 µg/dL (the current actionable level established by U.S. Centers for Disease Control and Prevention), SAM was well suited to investigate a potential behavioural signature of low-level lead exposure.
Lead exposure rarely occurs in isolation. Therefore, we examined the effects of lead together with another metal, manganese. Manganese is an essential nutrient, but can be neurotoxic at high levels. We hypothesized that exposure to both metals would produce unique cognitive effects.
Which methods did you use?
A total of 345 children from SAM were included in our study with cognitive testing data and biomarkers (blood lead and hair manganese ). We used latent profile analysis in an attempt to identify a behavioural signature. The continuous variables used for latent profile analysis classification included: (1) three tests from Cambridge Neuropsychological Test Automated Battery (CANTAB): Intra-Extra Dimensional Shift (IED), Spatial Span (SSP) and Stockings of Cambridge (SOC), (2) ten tasks from Woodcock-Muñoz Achievement Battery, Revised (W-M): Visual-Motor Integration, Verbal Comprehension (Vocabulary, Synonyms, Antonyms, Analogies), Visual-Auditory Comprehension, Concept Formation, Visual Spatial Thinking, Number Inversion and Spatial Relations, (3) Bender Gestalt task, and (4) Weschler block design task.
Once the optimal number of profiles for our data was determined, we assessed the association of blood lead level with the profiles, and tested for effect modification by hair manganese. Our motivation for this analysis was that, if a distinct cognitive profile was associated with the blood lead level, then low-level lead exposure may have a behavioural signature.
What are your key findings?
We found three unique profiles of cognitive test performance: high (13%), average (61%) and low (26%). A behavioural signature of low-level lead exposure did not emerge. Cognitive impairment was not localized to specific cognitive deficiency patterns. However, children with higher blood lead levels were more likely to be in lower performing profiles, independently of hair manganese levels.
What are the implications of your research?
We were unable to identify a behavioural signature of lead. Low-level lead exposure was associated with globally low cognitive performance. Interestingly, we noted stronger associations of blood lead levels with profile membership at lower lead exposure. The association became weaker as blood lead levels got higher. This is consistent with lack of a threshold for neurotoxic effects of lead.
We found no interaction between lead and manganese exposure. There are important considerations when assessing the cognitive impact of manganese exposure. The type of manganese biomarker (hair vs blood) may result in different scientific inferences. Furthermore, hair manganese levels in our sample were low, possibly reflecting nutritional status.
Why did you choose CANTAB for your project?
CANTAB is a well-validated and reliable instrument for cognitive assessment. In a sample of Spanish speakers, we preferred a set of tasks that was easily adaptable to our circumstances. We found the CANTAB tasks easy to administer and the data convenient to manage.
CANTAB tasks assess different cognitive domains. This provided us with useful data for identifying a potential behavioural signature of lead. As lead was theorized to impact executive functioning specifically, CANTAB’s Intra-Extra Dimensional Shift (IED), Spatial Span (SSP) and Stockings of Cambridge (SOC) were instrumentally important.
What are the next steps for your research?
SAM has multiple ongoing projects related to child wellbeing. These projects include: data collection on pesticide exposure and air pollution, analysis methodologies for assessment of metal mixtures, adolescent initiation into substance use, and assessment of neighbourhood processes related to child health. In the future, I hope to investigate how neighbourhood characteristics help or hinder cognitive development.
Seth Frndak, Epidemiology and Environmental Health Department at the University at Buffalo