DDT pesticide exposure may up Alzheimer's risk
"DDT: Pesticide linked to Alzheimer's," BBC News reports. A US study found that levels of the now banned pesticide DDT were almost four times higher in people with a confirmed diagnosis of Alzheimer's disease.
DDT was widely used as a pesticide during much of the 20th century, but is now banned in most countries because of concerns that it contaminates the environment and the food chain. The UK was relatively late in banning the pesticide, which did not come into force until 1984.
The BBC reports on a new case-control study involving 169 people, half with a confirmed diagnosis of Alzheimer's disease and half without. The researchers measured levels of dichlorodiphenyldichloroethylene (DDE), a breakdown product of DDT, in the participants' blood.
They calculated that people who had DDE levels in the top third of all those tested (the top 33%) were four times more likely to have Alzheimer's disease than those categorised in the bottom third (the bottom 33%).
However, as the Daily Mail usefully points out, "Not everyone exposed to DDT…develop[ed] Alzheimer's. Some Alzheimer's patients in the study had no trace of the chemical in their blood, and some healthy participants showed evidence of high exposure." This suggests that the relationship, if it does exist, is complex and influenced by many factors.
Where did the story come from?
The study was carried out by researchers from a range of US universities and environmental institutes, and was funded by grants from the US National Institutes of Health.
It was published in the peer-reviewed medical journal JAMA Neurology.
The media generally reported the study accurately. The Daily Mail, for example, provided useful balance from the scientists involved, stating that, "Not everyone exposed to DDT will develop Alzheimer's. Some Alzheimer's patients in the study had no trace of the chemical in their blood and some healthy participants showed evidence of high exposure."
The Mail went on to discuss how, "One deciding factor could be the presence or absence of a mutant gene called APOE, known to be strongly linked to Alzheimer's. Genetic risk factors such as APOE may combine with environmental factors such as exposure to pesticides to drive the disease forward, say the scientists." This was a fair account of the research.
However, the UK media failed to place the potential increase in relative risk into the wider context of what this represents in terms of an increase in actual risk. This would help readers understand whether the risk has quadrupled from extremely low to slightly less low, or whether it has risen from low risk to something they need to be concerned about.
What kind of research was this?
This was a case-control study comparing pesticide exposure in people with Alzheimer's with similar people who did not have the disease. The study aimed to find out if Alzheimer's was linked to the pesticide DDT, a chemical widely used in the past to spray crops and control malaria. It was banned in the UK after scientists found it was harmful to wildlife and the environment.
There have been concerns that DDT may be damaging to health, particularly in those likely to have high exposure, such as agricultural workers, but this isn't backed up by evidence.
The researchers also looked at whether genetics played a role in this potential link.
The authors point out that Alzheimer's disease is the most common neurodegenerative disease worldwide. Cases are expected to increase over the next few decades as the average age of the population in England rises.
This case-control study design cannot prove that exposure to DDT causes Alzheimer's. It can only prove that people with Alzheimer's tended to have more DDT in their bodies, which may or may not have contributed towards its development. There may be many explanations for this link and further research may one day explain the relationship more fully.
What did the research involve?
The study compared the levels of pesticide in the blood of 86 adults with Alzheimer's disease (the cases) with 79 similar people without the disease (the controls) to see if the amount of pesticide was related to their disease.
The causes of Alzheimer's are not firmly established, although it is thought to be caused by an combination of both environmental and genetic factors. Researchers recorded the genetic variation of a specific gene called APOE in all participants to see if this gene played any role in influencing the potential environmental pesticide-Alzheimer's link.
The study measured DDE levels in the blood, which is the chemical DDT is broken down to inside the body. In an effort to make the cases and controls similar, they were matched based on age, sex and race or ethnicity.
The statistical analysis was appropriate and compared different levels of DDE in the blood of cases and controls to see if it was related to the risk of disease.
What were the basic results?
The main results were as follows:
- DDE was detected in 70% of controls and 80% of cases.
- The average levels of DDE in the blood samples of the people with Alzheimer's disease (2.64 ng/mg cholesterol) were 3.8 times higher than those without the disease (0.69 ng/mg cholesterol). This was a statistically significant link.
- People who were categorised in the top third of DDE exposure (the top 33%) were 4.18 times (95% confidence interval [CI] 2.54 to 5.82) more likely to have Alzheimer's disease than those categorised in the lowest third (the bottom 33%) of DDE exposure.
- They found genetic variation in the APOE gene did significantly modify the environmental link between DDE exposure and Alzheimer's disease.
- DDE levels in the blood were highly correlated with DDE levels in the brain.
- No other pesticides besides DDE were found to be elevated in people with Alzheimer's disease compared with control participants.
- In an attempt to uncover a biological mechanism by which DDE may be causing Alzheimer's, the researchers added DDE to nerve cells in the laboratory, like those found in the brain. This exposure raised the levels of a molecule called amyloid precursor protein (APP) by "almost 50%". APP is known to be a risk factor for Alzheimer's disease, so this observation suggested a possible causal link.
People with Alzheimer's disease have abnormally high levels of APP inside their brain, and it is thought that these may contribute to the progressive damage to healthy brain cells.
How did the researchers interpret the results?
The researchers concluded that, "Elevated serum [blood] DDE levels are associated with an increased risk for AD [Alzheimer's disease] and carriers of an APOE4 ε4 allele [a genetic variation of the gene] may be more susceptible to the effects of DDE."
The researchers believe that, "Both DDT and DDE increase amyloid precursor protein levels, providing mechanistic plausibility for the association of DDE exposure with AD.
"Identifying people who have elevated levels of DDE and carry an APOE ε4 allele may lead to early identification of some cases of AD."
Conclusion
This small case-control study suggested DDT exposure (as measured by DDE levels in the blood) was linked to a higher risk of developing Alzheimer's disease. A potential biological mechanism for this link was put forward. The DDT-Alzheimer's risk link was found to be modified by genetic variation in a specific gene (APOE).
Importantly, this case-control study design cannot prove that exposure to DDT causes Alzheimer's disease directly. It can only prove that people with Alzheimer's disease in this study tended to have more DDT in their bodies, which may or may not have contributed towards them developing the disease.
The researchers' investigation into how DDE may be linked to amyloid precursor protein levels (known to be a risk factor for Alzheimer's disease) was brief and was only discussed in one paragraph in the research publication. This theory does offer a plausible explanation for how DDE might raise the risk of Alzheimer's, but is not proven at this stage.
Another limitation was that the study was small, involving just 165 people. Using such a small group of people increases the chances of false results. Studies using larger numbers of people will be needed to confirm or refute the proposed link and see whether it is real or widespread.
We should therefore be cautious about interpreting these results as proof that there is definitely a causal link between DDT and Alzheimer's.
If a causal link between DDT and Alzheimer's did exist, it is unlikely DDT would be the sole risk factor. The current consensus is that Alzheimer's is probably caused by a complex mixture of both genetic and environmental factors.
