Too much clean living may be contributing to a surge in cases of Alzheimer's disease in developed countries, experts believe.
Scientists have linked the "hygiene hypothesis" - the idea that lack of exposure to germs, viruses and parasites harms the immune system - to rising rates of Alzheimer's in richer nations.
Evidence shows that countries where the risk of infection is relatively low have more people suffering from Alzheimer's.
Likewise, better sanitation and the expansion of cities go hand in hand with higher incidence of the disease, the most common form of dementia.
Taken together, infection levels, sanitation and urbanisation account for 42.5% of the variation in rates of Alzheimer's between different countries.
Dr Molly Fox, from Cambridge University, who led the new research published in the journal Evolution, Medicine and Public Health, said: "The 'hygiene hypothesis', which suggests a relationship between cleaner environments and a higher risk of certain allergies and autoimmune diseases, is well established.
"We believe we can now add Alzheimer's to this list of diseases. There are important implications for forecasting future global disease burden, especially in developing countries as they increase in sanitation."
The scientists looked at the link between hygiene and Alzheimer's rates in 192 rich and poor countries. They adjusted the findings to take account of differences in birth rate, life expectancy and age structure.
Access to clean drinking water was one area said to have a high impact on Alzheimer's rates. Countries such as the UK and France, where this is universal, had a 9% higher incidence of Alzheimer's than countries such as Kenya and Cambodia where less than half the population can access clean water.
A similar pattern emerged from comparisons between countries with low and high rates of infectious disease.
Super-clean Switzerland and Iceland, with very low rates, were 12% more affected by Alzheimer's than China and Ghana, whose infection rates are high.
The more urbanised countries also experienced higher rates of Alzheimer's irrespective of life expectancy. In the UK and Australia, where more than three quarters of the population lived in urban areas, Alzheimer's incidence was 10% higher than in Bangladesh and Nepal, where less than a 10th of people had their homes in towns and cities.
Overall, differences in levels of sanitation, infectious disease and urbanisation accounted for 33%, 36% and 28% of the variation in Alzheimer's rate between countries.
Previous research has shown that Alzheimer's affects fewer people in Latin America, China and India than it does in Europe.
Even within those regions, prevalence is lower in urban than in rural areas, according to the new findings.
The hygiene hypothesis is based on the assumption that lack of contact with "dirt" in the form of bacteria and other infectious agents upsets the development of white blood cells, key elements of the immune system.
In particular, T-cells are said to be affected. T-cells have a variety of functions, including attacking and destroying foreign invaders and marshalling other parts of the immune system.
Some, known as "regulatory" T-cells, reign in the immune system when it starts to get out of control. Dysfunctional regulatory T-cells can lead to inflammation and autoimmune disorders.
Regulatory T-cell deficiency is linked to the type of inflammation commonly found in the brains of people with Alzheimer's disease.
The researchers wrote in their paper: "Exposure to micro-organisms is critical for the regulation of the immune system."
Since the turn of the 19th century, such exposure had increasingly diminished in wealthier nations due to lack of contact with "animals, faeces and soil".
"The increase in adult life expectancy and Alzheimer's prevalence in developing countries is perhaps one of the greatest challenges of our time," said Dr Fox.
"Today, more than 50% of people with Alzheimer's live in the developing world, and by 2025 it is expected that this figure will rise to more than 70%.
"A better understanding of how environmental sanitation influences Alzheimer's risk could open up avenues for both lifestyle and pharmaceutical strategies to limit Alzheimer's prevalence.
"An awareness of this by-product of increasing wealth and development could encourage the innovation of new strategies to protect vulnerable populations from Alzheimer's."
The hygiene hypothesis is normally thought to be most relevant in childhood, when the immune system is still developing. But in the case of Alzheimer's, exposure to microbes across a person's lifetime might be important, say the scientists. This is because regulatory T-cell numbers peak at various points in life, for example at adolescence and middle age.
Dr James Pickett, head of research at the Alzheimer's Society, said: "We known for some time that the numbers of people with Alzheimer's varies between countries. That this discrepancy could be the result of better hygiene is certainly an interesting theory and loosely ties in with the links we know exist between inflammation and the disease.
"However it is always difficult to pin causality to one factor and this study does not cancel out the role of the many other lifestyle differences such as diet, education and wider health which we know can also have a role to play.
"One in three people over 65 will develop dementia. The best way to reduce your risk is to eat a healthy diet, exercise regularly, not smoke and keep your blood pressure and cholesterol in check."
Dr Simon Ridley, head scientist at Alzheimer's Research UK, said: "Research has pointed to a complex relationship between inflammation, infection and Alzheimer's, and this is a key area of research in the search for new treatments for the disease.
"This is an intriguing finding, but we cannot conclude from these results that improved hygiene is a causal factor for Alzheimer's disease. It's important to note that the way Alzheimer's prevalence is reported can vary from one country to another, making comparisons between countries very difficult.
"Our risk of Alzheimer's is likely to be influenced by a complex mix of environmental and lifestyle factors, and this study did not investigate whether other factors beyond hygiene may be linked to any differing Alzheimer's risk in different countries. Research is essential for guiding public health policy, but policy decisions must take into account all available evidence on the potential benefits and harms of hygiene practices.
"Research to understand the different factors affecting the risk of Alzheimer's is crucial for finding preventions for the disease. Although there is not yet a sure fire way to prevent Alzheimer's, the risk can be reduced by eating a healthy, balanced diet, exercising regularly, not smoking and keeping blood pressure and cholesterol in check."