Growing up in countryside 'doubles Alzheimer's risk'...

“People who grew up in the countryside may be more than twice as likely to develop Alzheimer’s disease in old age” The Daily Telegraph reports.

While countryside living has traditionally been associated with a healthier lifestyle, the findings of a recent study suggest that this may not always be the case – at least in terms of Alzheimer’s disease.

The researchers pooled data from 13 individual studies, and examined the differences in the total number of people with dementia in the country compared to the city. The researchers also compared the number of new cases that developed over time in these two settings.

While they found no significant differences in the odds of developing dementia in general, they did find significant differences in the number of people who had Alzheimer’s.

People who grew up and continued to live in the country faced the highest increase in risk and were over twice as likely to have the disease compared to those who lived in more urban settings.

This is an intriguing study that, frustratingly, raises more questions than it answers. It is currently, in the words of the Daily Mail, ‘a mystery’ as to why growing up in a rural area would increase your risk of Alzheimer’s disease.

The researchers discuss the possibility that some type of childhood exposure to an environmental factor may be involved, but they freely admit that this is pure speculation.

They say that further high-quality research is needed to confirm this variation between geographical regions and to investigate potential causes of the observed differences.

Where did the story come from?

The study was carried out by researchers from the University of Edinburgh, University College London, and other UK organisations. The research was supported by Alzheimer Scotland, the Medical Research Council and other organisations throughout the UK.

The study was published in the peer-reviewed International Journal of Epidemiology.

The media coverage of this research was accurate. Both the Mail and the Telegraph pointed out that researchers have not explained why this difference in the number of Alzheimer’s cases appears. And that further studies are required to identify an underlying cause of the association.

What kind of research was this?

This was a systematic review and meta-analysis of studies that examined differences between rural and urban areas in dementia prevalence (overall number of people with dementia) and incidence (number of new cases of dementia that develop over a specific period of time, such as, over a year). The researchers included both cross-sectional and longitudinal studies in their review.

Pooling the results of multiple independent studies can paint a more complete picture than any given study on its own. Meta-analyses can provide a more powerful estimate of an association or effect size and increase our confidence in the result obtained, as the total number of participants included in such an analysis is larger than would be possible in a single study. However, there are important differences between studies that need to be considered when conducting and interpreting the results of a meta-analysis. For instance, in this review, the criteria used to diagnose dementia and Alzheimer’s varied between studies, as did the level at which the studies collected data (some used regional data, others collected data at the town or city level). The studies included in this review were conducted in many different countries; rural and city settings between countries may not be similar in terms of environmental or socioeconomic factors.

For example, a study in Japan defined ‘rural’ as being an administrative unit with a population of, or below, 30,000, while a study in Italy defined ‘rural’ as being a small town (specifically the Sicilian town of Troina) with limited transport links and an economy largely based on farming.

While some of the studies simply did not provide a definition of ‘rural’ as opposed to ‘urban’.

Finally, the results of a meta-analysis are only as good as the studies from which the data is taken. Studies with weak methodological quality may be used in the meta-analysis. While researchers often attempt to account for this by weighting each study based on quality, studies of variable rigor are generally included in the same review.

What did the research involve?

The study authors searched multiple databases to identify studies that reported the total number of dementia cases, or the number of new dementia cases, in rural settings, and compared these numbers to those seen in urban settings.

The researchers also included what is known as ‘grey literature’ - data not included in medical journals, but which may still be of value, such as research theses and government reports.

Researchers assessed the quality of the studies by considering study design, methodology, risk of bias, how cases were identified, standardisation of procedures across different study sites, and follow-up (in the case of longitudinal studies). The studies included in the meta-analysis ranged from poor to good quality.

For the meta-analysis, the researchers pooled the prevalence and incidence data from 13 studies to compare the odds of having or developing dementia in rural and urban participants. They conducted multiple sets of analyses, including one for dementia in general, as well as a separate analysis for studies that reported on Alzheimer’s disease in particular.

What were the basic results?

In total, 51 relevant studies were identified, 13 of which were included in the combined statistical analysis on dementia prevalence, and five were used in the dementia incidence meta-analysis. The studies used in the meta-analysis were published between 1996 and 2009, and were conducted in Nigeria, the USA, Taiwan, the UK, China, Peru, Mexico, India, Canada, Turkey and Italy.

When comparing the odds of all types of dementia, the researchers found:

no significant difference in the odds of having dementia (prevalence) between people living in rural and urban settings (odds ratio [OR] 1.11, 90% confidence interval [CI] 0.79 to 1.57)
no significant difference in the odds of developing dementia over the study period (incidence) between people living in rural and urban settings (OR 1.20, 90% CI 0.84 to 1.71)

When comparing the odds of Alzheimer’s disease, the researchers found:

a significant increase in the odds of having Alzheimer’s (prevalence) among people who lived in rural settings early in life, compared to urban dwellers (OR 2.22, 90% CI 1.19 to 4.16)
a significant increase in the odds of developing Alzheimer’s over the study period (incidence) among people who lived in rural settings early in life, compared to urban dwellers (OR 1.64, 90% CI 1.08 to 2.50)

How did the researchers interpret the results?

The researchers concluded that when “comparing rural and urban areas, there was evidence for an association between rurality and prevalence and incidence of Alzheimer’s disease.”

Conclusion

This systematic review and meta-analysis suggests that there may be an association between rural living and Alzheimer’s disease, but not with all types of dementia (such as vascular dementia – which is caused by reduced blood supply to the brain).

It is important to remember that this study can only show an association between setting and disease status, and does not tell us that growing up in a rural setting actually causes Alzheimer’s (or that living in an urban setting protects us from the disease). The study authors say that further work is needed to collect high quality evidence of geographical variation in dementia and Alzheimer’s risk.

They say that if the causes of the variation seen in this review can be determined, they could point to modifiable risk factors for the condition.

Again, this is pure speculation, but if an environmental factor that people were exposed to during their childhood was identified, then it may be possible to protect future generations against Alzheimer’s.

There are several limitations to this review that are important to consider, including:

The risks reported in this study were relative (the risk of Alzheimer’s compared between rural dwellers and urban dwellers), not absolute (your overall risk – ‘all things considered’). The percentage risk increase that this represents in absolute terms is unclear.
The definitions of dementia and Alzheimer’s, and the tools used to identify cases, varied across studies. The researchers report that none of the studies used specific diagnostic criteria to make a definite diagnosis, therefore the rates of dementia subtypes (including Alzheimer’s) “must be considered no more certain than ‘probable’” and that the “conclusions regarding specific dementia subtypes should be considered tentative.”
Many of the studies used different definitions of what constituted a rural environment and some studies provided no clear definition.
Most of the larger studies were conducted in middle to high income countries, so their findings may not apply to developing countries.
Many studies were looking at widely different geographical areas in terms of size – ranging from small districts to entire countries. These types of geographical variations can sometimes distort results (this is known as the ‘modifiable area unit problem’).
Finally, the review did not provide information on the studies included in the Alzheimer’s subtype analysis. It is unclear how many studies were included in this analysis, how many total participants these studies represented, where they were conducted, or how they were rated in terms of methodological quality. It is also unclear whether the Alzheimer’s analysis that compared rural vs. urban prevalence and incidence resulted in significant differences in risk, or if the only significant differences were seen among participants who grew up and remained in rural settings.

Overall, this systematic review and meta-analysis suggests that there may be a link between growing up and living in rural settings and risk of Alzheimer’s disease and raises some intriguing questions that warrant further research.

But, given the lack of a clear underlying cause, and the limitations of the study, this evidence is probably not enough to warrant upping sticks and moving to the city.