Cognition impaired by low-level exposure to organophosphate pesticides

A meta-analysis has concluded that low-level exposure to organophosphates has a small-to-moderate negative effect on cognitive function.

Organophosphate pesticides are the most widely used insecticides in the world; they are also (according to WHO), one of the most hazardous pesticides to vertebrate animals. While the toxic effects of high levels of organophosphates are well established, the effects of long-term low-level exposure are still controversial.

A meta-analysis involving 14 studies and more than 1,600 participants, reveals that the majority of well-designed studies undertaken over the last 20 years have found a significant association between low-level exposure to organophosphates and impaired cognitive function. Impairment was small to moderate, and mainly concerned psychomotor speed, executive function, visuospatial ability, working memory, and visual memory.

Working with solvents linked to cognitive problems in less-educated people

A study qualifies evidence that occupational exposure to solvents increases the risk of cognitive impairment later in life.

The study involved 4,134 people (average age 59) who worked at the French national gas and electric company, of whom most worked at the company for their entire career. Their lifetime exposure to chlorinated solvents, petroleum solvents, benzene and non-benzene aromatic solvents was estimated, and they were given the Digit Symbol Substitution Test to assess cognitive performance. Cognitive impairment was defined as scoring below the 25th percentile. Most of the participants (88%) were retired.

For analysis, participants were divided into two groups based on whether they had less than a secondary school education or not. This revealed an interesting finding: higher rates of solvent exposure were associated with cognitive impairment, in a dose-dependent relationship — but only in those with less than a high school education. Recency of solvent exposure also predicted worse cognition among the less-educated (suggesting that at least some of the damage was recoverable).

However, among those with secondary education or higher, there was no significant association between solvent exposure (quantity or recency) and cognition.

Over half the participants (58%) had less than a high school education. Of those, 32% had cognitive impairment — twice the rate in those with more education.

The type of solvent also made a difference, with non-benzene aromatic solvents the most dangerous, followed by benzene solvents, and then chlorinated and petroleum solvents (the rates of cognitive impairment among highly-exposed less-educated, was 36%, 24%, and 14%, respectively).

The findings point to the value of cognitive reserve, but I have several caveats. (Unfortunately, this study appears in a journal to which I don’t have access, so it’s possible the first of this at least is answered in the paper.) The first is that those with less education had higher rates of exposure, which raises the question of a threshold effect. Second is that the cognitive assessment is only at one point of time, lacking both a baseline (do we know what sort of average score adults of this age and with this little education would achieve? A quick online search threw up no such appropriate normative data) and a time-comparison that would give a rate of decline. Third, is that the cognitive assessment is very limited, being based on only one test.

In other words, the failure to find an effect among those with at least a high school education may well reflect the lack of sensitivity in the test (designed to assess brain damage). More sensitive tests, and test comparisons over time, may well give a different answer.

On its own, then, this finding is merely another data-point. But accumulating data-points is how we do science! Hopefully, in due course there’ll be a follow-up that will give us more information.

Air pollution linked to age-related cognitive decline

A large long-running study of older women has found a dose-dependent association between air pollution and cognitive decline. A review has found a dose-dependent association between air pollution and risk of heart attack.

Data from the Nurses' Health Study Cognitive Cohort, involving 19,409 older women (70-81), has found that higher levels of long-term exposure to air pollution were associated with faster rates of cognitive decline over a four-year period.

For each 10 micrograms per cubic meter of air increase in pollutants, cognitive decline was comparable to two years of age-related decline.

Pollution exposure was estimated from geography. Cognition was tested by three telephone interviews, administered at roughly two-year intervals.

Air pollution linked to heart attack risk

Given the association between cardiovascular risk factors and cognitive decline (“What’s good for the heart is good for the brain”), it’s worth noting that a review of 34 studies has found that every main air pollutant, with the exception of ozone, was significantly associated with greater risk of heart attack. For most of the pollutants, an increase in concentration of 10 micrograms per cubic meter of air – barely noticeable – was associated with a 1-3% increase in the chance of having a heart attack in the next week.

The size of the risk is small compared with traditional risk factors such as smoking status or hypertension or diabetes, but is something that those with other cardiovascular risk factors may want to consider. There’s also growing evidence that high levels of pollution increase stroke risk.

For more about the effects of air pollution on cognition

Pollutants' effect on cognition - news reports

Older news items (pre-2010) brought over from the old website

Prenatal exposure to urban air pollutants affects cognitive development

A study of 183 three-year-old children of non-smoking African-American and Dominican women residing in New York City has found that exposure during pregnancy to combustion-related urban air pollutants (specifically, polycyclic aromatic hydrocarbons) was linked to significantly lower scores on mental development tests and more than double the risk of developmental delay at age three.

[1096] Camann, D., Kinney P., Perera F. P., Rauh V. A., Whyatt R. M., Tsai W. - Y., et al. (2006).  Effect of Prenatal Exposure to Airborne Polycyclic Aromatic Hydrocarbons on Neurodevelopment in the First 3 Years of Life among Inner-City Children. Environmental Health Perspectives. 114(8), 1287 - 1292.

Full text available at http://www.ehponline.org/members/2006/9084/9084.pdf


Prenatal exposure to secondhand smoke increases risk of developmental delay

A new study funded by the National Institute of Environmental Health Sciences has found that children whose mothers are exposed during pregnancy to second-hand smoke have reduced scores on tests of cognitive development at age two, when compared to children from smoke-free homes. In addition, the children exposed to second-hand smoke during pregnancy are approximately twice as likely to have developmental scores below 80, which is indicative of developmental delay. These differences were magnified for children whose mothers lived in inadequate housing or had insufficient food or clothing during pregnancy. The combined effect results in a developmental deficit of about seven points in tests of cognitive performance.

Rauh, V.A., Whyatt, R.M., Garfinkel, R., Andrews, H., Hoepner, L., Reyes, A., Diaz, D., Camann, D. & Perera, F.P. 2004. Developmental effects of exposure to environmental tobacco smoke and material hardship among inner-city children. Neurotoxicology and Teratology, 26 (3), 373-385.


Older news items (pre-2010) brought over from the old website

Pollutants affect babies' brains

It appears that exposure to polychlorinated biphenyls (PCBs) in a mother's blood and breast milk can hinder the development of a baby's brain before and after birth. Although PCBs are now banned, these chemicals were once widely used in industry as coolants and lubricants and are still being leaked into the environment from old electrical equipment.

[591] Walkowiak, J., Wiener J. A., Fastabend A., Heinzow B., Krämer U., Schmidt E., et al. (2001).  Environmental exposure to polychlorinated biphenyls and quality of the home environment: effects on psychodevelopment in early childhood. Lancet. 358(9293), 1602 - 1607.


PCB-laden fish may affect adult verbal memory

The dangers of PCBs (once widely used as electrical insulators and lubricants and in paints and varnishes) have long been known, and assumed to apply chiefly to children and developing fetuses. A long-term study of those who eat the PCB-laden fish from Lake Michigan suggests for the first time that high levels of PCB may cause problems learning and remembering new verbal information in adults. In particular, those with high blood PCB levels had difficulties recalling a story told just 30 minutes earlier, and were less likely than their less-exposed peers to cluster words given orally into categories based on their meaning to boost recall.

Schantz, S.L., Gasior, D.M., Polverejan, E., McCaffrey, R.J., Sweeney, A.M., Humphrey, H.E.B. & Gardiner, J.C. 2001. Impairments of Memory and Learning in Older Adults Exposed to Polychlorinated Biphenyls via Consumption of Great Lakes Fish. Environmental Health Perspectives, 109 (6), 605.


How chronic exposure to solvents can impair the brain

Chronic occupational exposure to organic solvents, found in materials such as paints, printing and dry cleaning agents, has been linked to long-term cognitive impairment, but chronic solvent-induced encephalopathy (CSE) is still a controversial diagnosis. An imaging study of 10 CSE patients who had been exposed to solvents and had mild to severe cognitive impairment, 10 participants who had been exposed to solvents but had no CSE symptoms, and 11 participants who were not exposed to solvents and had no symptoms, has now found impairment in the frontal-striatal-thalamic (FST) circuitry of CSE patients. The disturbances are predictive of the clinical findings — impaired psychomotor speed and attention — and were also linked to exposure severity.

[989] van Dijk, F. J. H., Schene A. H., Heeten G. D. J., Visser I., Lavini C., Booij J., et al. (2008).  Cerebral impairment in chronic solvent-induced encephalopathy. Annals of Neurology. 63(5), 572 - 580.


Chemical in clear plastics can impair learning

A rat study has found that low doses of the environmental contaminant bisphenol–A (BPA), widely used to make many plastics found in food storage containers (including feeding bottles for infants), inhibit estrogen–induction of synaptic connections in the hippocampus, suggesting implications for children's learning ability. Also, when the ability to make estrogen is impaired, as in old age, exposure to BPA could adversely affect hippocampal function and contribute to age–related neurodegenerative diseases such as Alzheimer's disease, in which hippocampal function is impaired. The doses were below the current U.S. Environmental Protection Agency reference daily limit for human exposure.

[740] MacLusky, N. J., Hajszan T., & Leranth C. (2005).  The Environmental Estrogen Bisphenol A Inhibits Estradiol-Induced Hippocampal Synaptogenesis. Environmental Health Perspectives. 113(6), 675 - 679.



Older news items (pre-2010) brought over from the old website


Abnormal brain blood flow persisting in some Gulf War veterans

In a small study, some Gulf War syndromes are shown to have effects on the hippocampus that have persisted for 20 years, and in some cases worsened.

So-called ‘Gulf War syndrome’ is a poorly understood chronic condition associated with exposure to neurotoxic chemicals and nerve gas, and despite its name is associated with three main syndromes: impaired cognition (syndrome 1); confusion-ataxia (syndrome 2); central neuropathic pain (syndrome 3). Those with syndrome 2 are the most severely affected. Note that the use of the term ‘impaired cognition’ for syndrome 1 is not meant to indicate that the other syndromes show no impaired cognition; rather, it signals the absence of other primary symptoms such as ataxia and pain.

Symptoms of Gulf War syndrome include fatigue, neuropathic pain, memory and concentration deficits, balance disturbances and depression. Many of these symptoms suggest impairment of the hippocampus (among other regions, in particular the basal ganglia).

The new study follows up on an earlier study, with many of the same participants involved. A new, more sensitive, technique for assessing blood flow in the hippocampus was used to assess 35 patients with Gulf War syndromes and 13 controls. In the study of eleven years previous, those with syndrome 1 (impaired cognition) showed similar responses as the controls, while those with syndrome 2 (confusion-ataxia) showed abnormal blood flow in the right hippocampus.

In the present study, that abnormal hippocampal blood flow had progressed to the left hippocampus for those with syndrome 2 and to both hippocampi for those with syndrome 3. The results indicate that this alteration of hippocampal blood flow persists and can even worsen.

Around a quarter of U.S. military personnel deployed to the 1991 Persian Gulf War are estimated to be affected by Gulf War syndrome. Previous research has suggested genetic variation may underlie individuals’ vulnerability to neurotoxins.

High levels of city pollution linked to brain damage in children

A small Mexican study provides more evidence for the negative effect of pollution on developing brains, with cognitive impairment linked to reduced white matter in specific regions.

In yet another study of the effects of pollution on growing brains, it has been found that children who grew up in Mexico City (known for its very high pollution levels) performed significantly worse on cognitive tests than those from Polotitlán, a city with a strong air quality rating.

The study involved 30 children aged 7 or 8, of whom 20 came from Mexico City, and 10 from Polotitlán. Those ten served as controls to the Mexico City group, of whom 10 had white matter hyperintensities in their brains, and 10 had not. Regardless of the presence of lesions, MC children were found to have significantly smaller white matter volumes in right parietal and bilateral temporal regions. Such reduced volumes were correlated with poorer performance on a variety of cognitive tests, especially those relating to attention, working memory, and learning.

It’s suggested that exposure to air pollution disturbs normal brain development, resulting in cognitive deficits.

One cause of damage in older brains, and how exercise can help

Two mice studies indicate that an increase in a protein involved in immune response may be behind the reduced ability of older brains to create new neurons, and that exercise produces a protein that helps protect against damage caused by illness, injury, surgery and pollutants.

In the first mouse study, when young and old mice were conjoined, allowing blood to flow between the two, the young mice showed a decrease in neurogenesis while the old mice showed an increase. When blood plasma was then taken from old mice and injected into young mice, there was a similar decrease in neurogenesis, and impairments in memory and learning.

Analysis of the concentrations of blood proteins in the conjoined animals revealed the chemokine (a type of cytokine) whose level in the blood showed the biggest change — CCL11, or eotaxin. When this was injected into young mice, they indeed showed a decrease in neurogenesis, and this was reversed once an antibody for the chemokine was injected. Blood levels of CCL11 were found to increase with age in both mice and humans.

The chemokine was a surprise, because to date the only known role of CCL11 is that of attracting immune cells involved in allergy and asthma. It is thought that most likely it doesn’t have a direct effect on neurogenesis, but has its effect through, perhaps, triggering immune cells to produce inflammation.

Exercise is known to at least partially reverse loss of neurogenesis. Exercise has also been shown to produce chemicals that prevent inflammation. Following research showing that exercise after brain injury can help the brain repair itself, another mouse study has found that mice who exercised regularly produced interleukin-6 (a cytokine involved in immune response) in the hippocampus. When the mice were then exposed to a chemical that destroys the hippocampus, the interleukin-6 dampened the harmful inflammatory response, and prevented the loss of function that is usually observed.

One of the actions of interleukin-6 that brings about a reduction in inflammation is to inhibit tumor necrosis factor. Interestingly, I previously reported on a finding that inhibiting tumor necrosis factor in mice decreased cognitive decline that often follows surgery.

This suggests not only that exercise helps protect the brain from the damage caused by inflammation, but also that it might help protect against other damage, such as that caused by environmental toxins, injury, or post-surgical cognitive decline. The curry spice cucurmin, and green tea, are also thought to inhibit tumor necrosis factor.

Air pollution impacts cognitive performance

A study of Michigan public schools, and a mouse study, add to growing evidence that high levels of air pollution negatively affect learning and memory.

Following several recent studies pointing to the negative effect of air pollution on children’s cognitive performance (see this April 2010 news report and this May 2011 report), a study of public schools in Michigan has found that 62.5% of the 3660 schools in the state are located in areas with high levels of industrial pollution, and those in areas with the highest industrial air pollution levels had the lowest attendance rates and the highest proportions of students who failed to meet state educational testing standards in English and math. Attendance rates are a potential indicator of health levels.

Minority students were especially hit by this — 81.5% of African American and 62.1% of Hispanic students attend schools in the top 10% of the most polluted areas, compared to 44.4% of white students.

Almost all (95%) of the industrial air pollution around schools comes from 12 chemicals (diisocyanates, manganese, sulfuric acid, nickel, chlorine, chromium, trimethylbenzene, hydrochloric acid, molybdenum trioxide, lead, cobalt and glycol ethers) that are all implicated in negative health effects, including increased risk of respiratory, cardiovascular, developmental and neurological disorders, as well as cancer.

There are potentially two issues here: the first is that air pollution causes health issues which lower school attendance and thus impacts academic performance; the other is that the pollution also directly effects the brain, thus affecting cognitive performance.

A new mouse study looking at the effects of air pollution on learning and memory has now found that male mice exposed to polluted air for six hours a day, five days a week for 10 months (nearly half their lifespan), performed significantly more poorly on learning and memory tasks than those male mice living in filtered air. They also showed more signs of anxiety- and depressive-like behaviors.

These changes in behavior and cognition were linked to clear differences in the hippocampus — those exposed to polluted air had fewer dendritic spines in parts of the hippocampus (CA1 and CA3 regions), shorter dendrites and overall reduced cell complexity. Previous mouse research has also found that such pollution causes widespread inflammation in the body, and can be linked to high blood pressure, diabetes and obesity. In the present study, the same low-grade inflammation was found in the hippocampus. The hippocampus is particularly sensitive to damage caused by inflammation.

The level of pollution the mice were exposed to was equivalent to what people may be exposed to in some polluted urban areas.

Exposure to vehicle pollution bad for brains old and young

Two recent studies have come out implicating traffic pollutants as factors in age-related cognitive decline and dementia and as prenatal risk factors for attention problems.

A study in which mice were exposed to polluted air for three 5-hour sessions a week for 10 weeks, has revealed that such exposure damaged neurons in the hippocampus and caused inflammation in the brain. The polluted air was laden with particles collected from an urban freeway.

Another recent study found that, of 215 children, those whose cord blood showed high levels of combustion-related pollutants such as polycyclic aromatic hydrocarbons (PAH), had more attention (and anxiety) problems at ages 5 and 7. The children were born to nonsmoking African-American and Dominican women residing in New York City.

Prenatal exposure to common insecticide linked to lower IQ at age 7

Two longitudinal studies, one rural and one urban, have reported an association between prenatal pesticide exposure and significantly lower IQ at age 7.

A study of 265 New York City minority children has found that those born with higher amounts of the insecticide chlorpyrifos had lower IQ scores at age 7. Those most exposed (top 25%) scored an average 5.3 points lower on the working memory part of the IQ test (WISC-IV), and 2.7 points lower on the full IQ test, compared to those in the lowest quartile.

The children were born prior to the 2001 ban on indoor residential use of the common household pesticide in the US. The babies' umbilical cord blood was used to measure exposure to the insecticide.

Previous research had found that, prior to the ban, chlorpyrifos was detected in all personal and indoor air samples in New York, and 70% of umbilical cord blood collected from babies. The amount of chlorpyrifos in babies' blood was associated with neurodevelopmental problems at age three. The new findings indicate that these problems persist.

While exposure to the organophosphate has measurably declined, agricultural use is still permitted in the U.S.

Similarly, another study, involving 329 7-year-old children in a farming community in California, has found that those with the highest prenatal exposure to the pesticide dialkyl phosphate (DAP) had an average IQ 7 points lower than children whose exposure was in the lowest quintile. Prenatal pesticide exposure was linked to poorer scores for working memory, processing speed, verbal comprehension, and perceptual reasoning, as well as overall IQ.

Prenatal exposure was measured by DAP concentration in the mother’s urine. Urine was also collected from the children at age 6 months and 1, 2, 3½ and 5 years. However, there was no consistent link between children’s postnatal exposure and cognition.

While this was a farming community where pesticide exposure would be expected to be high, the levels were within the range found in the general population.

It’s recommended that people wash fruit and vegetables thoroughly, and limit their use of pesticides at home.

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