̽��ֱ�� of Cambridge - Molly Fox

Better hygiene in wealthy nations may increase Alzheimer’s risk

fpjl2 — Wed, 04 Sep 2013 10:01:20 +0000

New research has found a “very significant” relationship between a nation’s wealth and hygiene and the Alzheimer’s “burden” on its population. High-income, highly industrialised countries with large urban areas and better hygiene exhibit much higher rates of Alzheimer’s.

Using ‘age-standardised’ data - which predict Alzheimer’s rates if all countries had the same population birth rate, life expectancy and age structure - the study found strong correlations between national sanitation levels and Alzheimer’s.

This latest study adds further weight to the “hygiene hypothesis” in relation to Alzheimer’s: that sanitised environments in developed nations result in far less exposure to a diverse range of bacteria, viruses and other microorganisms - which might actually cause the immune system to develop poorly, exposing the brain to the inflammation associated with Alzheimer’s disease, say the researchers.

“ ̽��ֱ��‘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,” said Dr Molly Fox, lead author of the study and Gates Cambridge Alumna, who conducted the research at Cambridge’s Biological Anthropology division.

“There are important implications for forecasting future global disease burden, especially in developing countries as they increase in sanitation.”

̽��ֱ��researchers tested whether “pathogen prevalence” can explain the levels of variation in Alzheimer’s rates across 192 countries.

After adjusting for differences in population age structures, the study found that countries with higher levels of sanitation had higher rates of Alzheimer’s. For example, countries where all people have access to clean drinking water, such as the UK and France, have 9% higher Alzheimer’s rates than countries where less than half have access, such as Kenya and Cambodia.

Countries that have much lower rates of infectious disease, such as Switzerland and Iceland, have 12% higher rates of Alzheimer’s compared with countries with high rates of infectious disease, such as China and Ghana.

More urbanised countries exhibited higher rates of Alzheimer’s, irrespective of life expectancy. Countries where more than three-quarters of the population are located in urban areas, such as the UK and Australia, exhibit 10% higher rates of Alzheimer’s compared to countries where less than one-tenth of people inhabit urban areas, such as Bangladesh and Nepal.

Differences in levels of sanitation, infectious disease and urbanisation accounted respectively for 33%, 36% and 28% of the discrepancy in Alzheimer’s rates between countries.

Researchers said that, although these trends had “overlapping effects”, they are a good indication of a country’s degree of hygiene which, when combined, account for 42.5% of the “variation” in countries’ Alzheimer’s disease rates - showing that countries with greater levels of hygiene have much higher Alzheimer’s rates regardless of general life expectancy.

Previous research has shown that in the developed world, dementia rates doubled every 5.8 years compared with 6.7 years in low income, developing countries; and that Alzheimer’s prevalence in Latin America, China and India are all lower than in Europe, and, within those regions, lower in rural compared with urban settings - supporting the new study’s findings.

̽��ֱ��results of the study are newly published by the journal Evolution, Medicine and Public Health, with these latest results coming hard on the heels of previous research led by Fox on the benefits of breastfeeding for Alzheimer’s prevention.

“Exposure to microorganisms is critical for the regulation of the immune system,” write the researchers, who say that say that - since increasing global urbanisation beginning at the turn of the 19th century - the populations of many of the world’s wealthier nations have increasingly very little exposure to the so-called ‘friendly’ microbes which “stimulate” the immune system - due to “diminishing contact with animals, faeces and soil.”

Aspects of modern life - antibiotics, sanitation, clean drinking water, paved roads and so on - lead to lower rates of exposure to these microorganisms that have been “omnipresent” for the “majority of human history”, they say.

This lack of microbe and bacterial contact can lead to insufficient development of the white blood cells that defend the body against infection, particularly those called T-cells - the foot soldiers of the immune system that attack foreign invaders in the bloodstream.

Deficiency of anti-inflammatory (“regulatory”) T-cells has links to the types of inflammation commonly found in the brain of those suffering with Alzheimer’s disease, and the researchers’ proposal that Alzheimer’s risk is linked to the general hygiene levels of a nation’s population is reinforced by their analysis of global Alzheimer’s rates.

“ ̽��ֱ��increase in adult life expectancy and Alzheimer’s prevalence in developing countries is perhaps one of the greatest challenges of our time. 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%,” said Fox.

“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.”

While childhood - when the immune system is developing - is typically considered critical to the ‘hygiene hypothesis’, the researchers say that regulatory T-cell numbers peak at various points in a person’s life - adolescence and middle age for example - and that microorganism exposure across a lifetime may be related to Alzheimer’s risk, citing previous research showing fluctuations in Alzheimer’s risk in migrants.

̽��ֱ��team used the disability-adjusted life year (DALY) rates to calculate the incidence of Alzheimer’s across the countries studied. ̽��ֱ��DALY measurement is the sum of years lost due to premature mortality combined with years spent in disability – the World Health Organisation (WHO) says that one DALY can be thought of as “one lost year of ‘healthy’ life”.

̽��ֱ��researchers say this method is a much better measure than death rates as it “omits the effects of differential mortality rates” between developed and developing countries. ̽��ֱ��study was based on the WHO’s ‘Global Burden of Disease’ report, which presents world dementia data for 2004.

People living in industrialised countries may be more likely to develop Alzheimer’s due to greatly reduced contact with bacteria, viruses and other microorganisms - which can lead to problems with immune development and increased risk of dementia, suggests a new study.

There are important implications for forecasting future global disease burden, especially in developing countries as they increase in sanitation

Molly Fox

Better hygiene in wealthy nations may increase Alzheimer's risk

Prempcc via Flickr

Wash your hands

Age-standardised data

̽��ֱ��process of age-standardisation presents a “single summary rate that reflects the number of events that would have been expected if the populations being compared had had identical age distribution” (WHO 2001)

̽��ֱ��age-standardised data is calculated by adjusting the crude data for 5-year age groups by age-weights reflecting the age-distribution of the standard population. In the version of the WHO’s Global Burden of Disease report we utilised, the terminal age category has been extended from the previous 85+ to 100+, which allows for better adjustment for differences in the proportion of population in older strata.

̽��ֱ��age-adjusted and disability-adjusted life year (DALY) rates are calculated by “adjusting the crude estimates to an artificial population structure, the WHO Standard Population, that closely reflects the age and sex structure of most low and middle income countries” (WHO 2013).

̽��ֱ��effort to construct a standard population for comparing data across populations with varied age-structures began in the 1840s, and progressed to an international scale in 1960 and was then adopted by the WHO. Statisticians have been researching and improving this process for the past five decades.

̽��ֱ��new WHO World Standard was developed in 2000 to best reflect projections of world age-structures for the period 2000-2025. This new standard is based on the UN Population Division’s assessments every two years and future projections for every five years of each country’s population age-structure. This standardised procedure is widely accepted across the world, and is the basis for all relevant WHO-sponsored analyses.

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Breastfeeding may reduce Alzheimer’s risk

tdk25 — Mon, 05 Aug 2013 08:04:23 +0000

Mothers who breastfeed their children may have a lower risk of developing Alzheimer’s Disease, with longer periods of breastfeeding also lowering the overall risk, a new study suggests.

̽��ֱ��report, newly published in the Journal of Alzheimer’s Disease, suggests that the link may be to do with certain biological effects of breastfeeding. For example, breastfeeding restores insulin tolerance which is significantly reduced during pregnancy, and Alzheimer’s is characterised by insulin resistance in the brain.

Although they used data gathered from a very small group of just 81 British women, the researchers observed a highly significant and consistent correlation between breastfeeding and Alzheimer’s risk. They argue that this was so strong that any potential sampling error was unlikely.

At the same time, however, the connection was much less pronounced in women who already had a history of dementia in their family. ̽��ֱ��research team hope that the study – which was intended merely as a pilot – will stimulate further research looking at the relationship between female reproductive history and disease risk.

̽��ֱ��findings may point towards new directions for fighting the global Alzheimer’s epidemic – especially in developing countries where cheap, preventative measures are desperately needed.

More broadly, the study opens up new lines of enquiry in understanding what makes someone susceptible to Alzheimer’s in the first place. It may also act as an incentive for women to breastfeed, rather than bottle-feed – something which is already known to have wider health benefits for both mother and child.

Dr Molly Fox, from the Department of Biological Anthropology at the ̽��ֱ�� of Cambridge, who led the study, said: “Alzheimer’s is the world’s most common cognitive disorder and it already affects 35.6 million people. In the future, we expect it to spread most in low and middle-income countries. So it is vital that we develop low-cost, large-scale strategies to protect people against this devastating disease.”

Previous studies have already established that breastfeeding can reduce a mother’s risk of certain other diseases, and research has also shown that there may be a link between breastfeeding and a woman’s general cognitive decline later in life. Until now, however, little has been done to examine the impact of breastfeeding duration on Alzheimer’s risk.

Fox and her colleagues – Professor Carlo Berzuini and Professor Leslie Knapp – interviewed 81 British women aged between 70 and 100. These included both women with, and without, Alzheimer’s. In addition, the team also spoke to relatives, spouses and carers.

Through these interviews, the researchers collected information about the women’s reproductive history, their breastfeeding history, and their dementia status. They also gathered information about other factors that might account for their dementia, for example, a past stroke, or brain tumour.

Dementia status itself was measured using a standard rating scale called the Clinical Dementia Rating (CDR). ̽��ֱ��researchers also developed a method for estimating the age of Alzheimer’s sufferers at the onset of their disease, using the CDR as a basis and taking into account their age and existing, known patterns of Alzheimer’s progression. All of this information was then compared with the participants’ breastfeeding history.

Despite the small number of participants, the study revealed a number of clear links between breastfeeding and Alzheimer’s. These were not affected when the researchers took into account other potential variables such as age, education history, the age when the woman first gave birth, her age at menopause, or her smoking and drinking history.

̽��ֱ��researchers observed three main trends:

• Women who breastfed exhibited a reduced Alzheimer’s Disease risk compared with women who did not.

• Longer breastfeeding history was significantly associated with a lower Alzheimer’s Risk.

• Women who had a higher ratio of total months pregnant during their life to total months breastfeeding had a higher Alzheimer’s risk.

̽��ֱ��trends were, however, far less pronounced for women who had a parent or sibling with dementia. In these cases, the impact of breastfeeding on Alzheimer’s risk appeared to be significantly lower, compared with women whose families had no history of dementia.

̽��ֱ��study argues that there may be a number of biological reasons for the connection between Alzheimer’s and breastfeeding, all of which require further investigation.

One theory is that breastfeeding deprives the body of the hormone progesterone, compensating for high levels of progesterone which are produced during pregnancy. Progesterone is known to desensitize the brain’s oestrogen receptors, and oestrogen may play a role in protecting the brain against Alzheimer’s.

Another possibility is that breastfeeding increases a woman’s glucose tolerance by restoring her insulin sensitivity after pregnancy. Pregnancy itself induces a natural state of insulin resistance. This is significant because Alzheimer’s is characterised by a resistance to insulin in the brain (and therefore glucose intolerance) to the extent that it is even sometimes referred to as “Type 3 diabetes”.

“Women who spent more time pregnant without a compensatory phase of breastfeeding therefore may have more impaired glucose tolerance, which is consistent with our observation that those women have an increased risk of Alzheimer’s disease,” Fox added.

̽��ֱ��full paper: Maternal Breastfeeding History and Alzheimer’s Disease Risk can be found here.

For more information about this story, please contact Tom Kirk, Tel: 01223 332300, thomas.kirk@admin.cam.ac.uk

A new study suggests that mothers who breastfeed run a lower risk of developing Alzheimer’s, with longer periods of breastfeeding further reducing the risk.

In the future, we expect Alzheimer's to spread most in low and middle-income countries, so it is vital that we develop low-cost, large-scale strategies to protect people against it.

Molly Fox

Anton Nossik via Wikimedia Commons

Breastfeeding.

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̽��ֱ��importance of grandmothers in the lives of their grandchildren

bjb42 — Thu, 29 Oct 2009 00:00:00 +0000

According to the "Grandmother Hypothesis," post-menopausal women can increase their genetic contribution to future generations by increasing the survivorship of their grandchildren.

While some demographic studies have found evidence for this theory, others have found little support for it.

A team led by biological anthropologist Leslie Knapp in the Department of Biological Anthropology have discovered that a grandmother's effect on grandchildren varies according to their X-chromosome relatedness.

̽��ֱ��research was carried out by a re-evaluation of the birth and death records of seven populations in Asia, North America, Europe and Africa who had lived in different periods dating back to the 17th century.

By specifically looking at child mortality in the first three years of life it was found that a grandmothers' effect on grandchildren varies according to their X-chromosome relatedness.

It was discovered that the effect of a grandmother's presence on grandchild survivorship corresponds relatively with her X-relatedness to the grandchild, which is not equivalent in boys and girls.

Specifically, maternal grandmothers have 25% X relatedness with both grandsons and granddaughters and both grandchildren are equally likely to inherit any one of her X-linked genes.

Contrastingly, paternal grandmothers will pass on one of her X chromosomes to their granddaughters (making them 50% X-related) but she will not pass this chromosome on to her grandson (making them 0% X-related).

Molly Fox, Gates Cambridge Scholar at the Department of Biological Anthropology said : "We suggest that maternal and paternal grandmothers have different incentive to invest in grandsons and granddaughters, due to differences in genetic relatedness.

" ̽��ֱ��presence of a paternal grandmother in all seven of the populations had a harmful effect on grandsons because her presence was linked with an increase in mortality.

"Meanwhile, in six out of seven populations, the paternal grandmother's presence in her granddaughter's early life had a beneficial effect in terms of the risk of mortality. This difference between paternal grandsons and granddaughters would explain a lot of the inconsistencies in previous studies, where the sex of the grandchild was not considered.

"We've only looked at child mortality, and the mechanism itself remains mysterious. Other studies have given evidence against conscious favouritism towards one grandchild or another".

It is widely believed that women live long post-reproductive lives to help care for their grandchildren and the "Grandmother Hypothesis" is based on the fact that women are genetically related to their grandchildren. ̽��ֱ��results suggest that the nature of that genetic relatedness should not be overlooked since boys and girls differ in the percent of genes they share with maternal versus paternal grandmothers based on differences in X-chromosome inheritance.

Biologists use genetic relatedness between family members to explain the evolution of not only longevity, but also altruism, kin investment, offspring recognition, parenting strategies, and tribe formation, and so reconsidering the genetic relatedness between grandmothers and grandchildren has implications throughout the field of human evolution.

It is widely believed that women live long post-reproductive lives to help care for their grandchildren. Now research suggests that the pattern may differ depending on the relationship between grandmother and grandchild.

We suggest that maternal and paternal grandmothers have different incentives to invest in grandsons and granddaughters, due to differences in genetic relatedness.

Molly Fox

dok1 from Flickr

Korean Grandmother and Baby

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