Cleanliness does not 'cause dementia'

“Being too clean could increase your risk of developing Alzheimer’s,” The Sun has reported, while the Daily Mail reports that “an obsession with being too clean and hygienic could lead to a higher risk of dementia”.

The reports refer to research into the association between a country’s economic development, sanitation and clean water, the prevalence of infectious bugs, and a statistical estimate of Alzheimer’s disease.

Countries with higher levels of pathogens, poorer sanitation and hygiene systems and lower economic development had lower rates of Alzheimer’s disease. However, flaws in the research limit our ability to draw conclusions based on the study’s results.

Media reports suggesting that being clean causes Alzheimer's disease cannot be backed up because the study can’t prove cause and effect. The causes of Alzheimer’s disease are largely unknown, with genetic factors and age being the most established risk factors. If there is a link between a country’s economics and sanitation and risk of Alzheimer’s disease, it could be due to confounding from other environmental and sociodemographic factors, rather than being a direct effect of sanitation and pathogen exposure alone.

Where did the story come from?

The study was carried out by researchers from the University of Cambridge, University of Glasgow, University of Utah and McMaster University in Canada. The study was funded by the Economic and Social Research Council and Gonville & Caius College, Cambridge.

The study was published open access in the peer-reviewed journal, Evolution, Medicine, and Public Health.

Media coverage tended to focus rather uncritically on the link between access to clean water, low prevalence of parasites and other disease-causing agents and increased risk of Alzheimer’s disease. The Mail Online did, however, publish quotes regarding the difficulty of identifying individual causes of the disease.

Lacking from both the media coverage and the research article was any discussion on the association between these pathogens (including those that cause malaria, tuberculosis and leprosy), hygienic or sanitary environments and infectious diseases.

What kind of research was this?

This study used the "hygiene hypothesis" in relation to Alzheimer’s disease. The researchers thought that Alzheimer’s would be positively associated with sanitation (as sanitation levels increased, they expected the number of new Alzheimer’s disease cases to increase as well).

The hygiene hypothesis states that the clean and hygienic conditions (such as clean drinking water, availability of antibiotics, non-dirt flooring in houses) are associated with a reduced exposure to bacteria, parasites and other pathogens. This lack of exposure, especially in early childhood, is thought to be associated with changes in the development of the immune system. This is in turn thought to be associated with increased autoimmune disorders, where a dysfunctional immune system causes illness instead of protecting against it.

While the causes of Alzheimer’s disease are not fully understood, researchers suggest that the symptoms seen in the disease are the result of an autoimmune response. They tested the hypothesis that this is associated with low levels of microbial diversity in developed countries due to high levels of sanitation and hygienic environments.

What did the research involve?

The researchers modelled the association between diversity of microbes in a population and Alzheimer’s disease using “regression analysis”. Due to difficulties in directly measuring cases of Alzheimer’s disease and the deaths it causes, they used a measure called the age-standardised Alzheimer’s Disease Disability Adjusted Life Year (AD DALY) as their main outcome measure. A proxy measure for microbial diversity was used as well, where the prevalence of certain microbes was taken as an indication of the number of different microbes a person would be exposed to across their lifetime in different parts of the world.

The researchers included multiple variables in their model in order to test the hygiene hypothesis for Alzheimer’s. These included:

• the historical prevalence of several parasites and other pathogens that cause infectious diseases
• the proportion of the population with access to clean water and other sanitation measures
• the national infant mortality rate
• the gross national income per capita and gross domestic product (economic measures)
• the proportion of the population living in urban areas

The researchers used the regression model to determine whether the above variables were related to AD DALY, and how the relationship between pathogen prevalence and AD DALY rates varied in different countries.

What were the basic results?

The researchers found that high levels of pathogens were associated with lower rates of Alzheimer’s disease, and that higher levels of hygiene (which was taken to be a marker of "potentially lower degree of micro-organism exposure") were associated with higher Alzheimer’s disease rates.

The researchers found that countries with higher pathogen prevalence and higher infant mortality rates were associated with lower Alzheimer’s disease rates (a negative correlation). While countries with higher levels of hygiene (more people with exposure to clean drinking water, improved sanitation facilities), those with higher gross national income and gross domestic product, and more people living in urban settings had higher rates of age-adjusted Alzheimer’s Disease Disability Adjusted Life Years.

In a slight variation from the hygiene hypothesis, the analyses found that greater exposure to microbes across the lifespan, not just in early childhood, is associated with reduced Alzheimer’s rates.

How did the researchers interpret the results?

The researchers concluded that their results support the hygiene hypothesis for Alzheimer’s, and that “variation in hygiene may partly explain global patterns in AD rates”. They further suggest that the results “may help predict AD burden in developing countries where microbial diversity is rapidly diminishing” and that “epidemiological forecasting is important for preparing for future healthcare needs and research prioritisation”.

Conclusion

This study suggests that proxy measures for exposure to microbes and living in sanitary and hygienic environments may be associated with increased rates of Alzheimer’s disease.

The researchers point out that their study, as with all epidemiological studies based on survey data, are limited in as much as they can only provide information on correlations and cannot be interpreted as proving one factor causes another.

Relying on survey data, especially data from different countries, is also limited by the fact that it is collected in different ways. It is important to evaluate the source of the data – the current study investigation used data from the World Health Organization’s Global Burden of Disease report to establish Alzheimer’s outcomes. This report compiles age-standardised figures based on disease registers, population surveys and previously published epidemiological data. While it is standard (and essential) to adjust such data for demographic variation across countries (such as population age structure, life expectancy at birth) it can be more difficult to account for variation in disease reporting, especially for an illness that does not have a standard diagnostic test.

The researchers report that there is considerable debate regarding the association between exposure to microbes and Alzheimer’s disease. Among researchers interested in this possible relationship, there is varying opinion on the direction and strength of any association. Some think that exposure to microbes early in childhood has a detrimental effect on immune system development, and in that way increases Alzheimer’s disease risk. Others have asserted that problems with the immune system and Alzheimer’s disease are linked, but the direction of the association is not known based on the current evidence. The researchers who conducted the current study suggest that the link is due to a lack of exposure to microbes early in life.

While these are possible theories, as the causes of Alzheimer’s disease remain unknown it is possible that the observed link could be influenced by confounding from other environmental and sociodemographic factors that differ between countries of high and low sanitation. In any case, there is unlikely to be a single risk factor for Alzheimer’s disease, and it is likely to be an accumulation of several factors.

In the face of these limitations and disagreements, the evidence on any possible link between sanitary and hygienic environments and the risk of developing Alzheimer’s remains uncertain.