Low linguistic ability in early life linked to Alzheimer’s later on

Nun Study as unique source for the long-term Alzheimer’s research

In 1991, David A. Snowdon, Ph.D., Professor at Sanders-Brown Center on Aging College of Medicine, University of Kentucky, Lexington, began what has come to be known as the Nun Study. Participants in this study are 678 American members of the School Sisters of Notre Dame religious congregation. The nuns in the study are age 75 to 106.

The Nun Study is an ongoing, one-of-a-kind resource for the study of brain diseases in the elderly. It is expected that data, tissue, and genetic material collected in this study will be used by scientists for decades into the future.

Each of the 678 participants in the Nun Study agreed to participate in annual assessments of their cognitive and physical function, medical exams, blood drawing for genetic and nutritional studies, and brain donation at death for neuropathologic studies. The Nun Study represents the largest brain donor population in the world. In addition, the sisters have given investigators full access to their convent and medical records. The convent archives are particularly useful in our study of Alzheimer's disease because they contain accurate risk factor data spanning the entire lifespan of the participants. Accurate information on early and mid-life risk factors is difficult or impossible to obtain in most other studies on Alzheimer's disease because individuals with this memory disorder cannot accurately recall their history. The convent archives contain a wealth of information including baptismal records, birth certificates, socioeconomic characteristics of the family, education documentation, autobiographies written in early, mid, and late life, as well as residential, social, and occupational data describing their mid and late lives.

Many factors that confound (or confuse) the findings of other studies are either eliminated or minimized because of the relatively homogeneous adult lifestyles and environments of these women. Participants in this study are non-smokers, drink little if any alcohol, have the same marital status and reproductive history, have lived in similar housing, held similar jobs, and had similar access to preventive and medical care.

Findings from Nun Study

Some of the findings received from the Nun Study confirm the results, received from other researches, but there are some absolutely new insights obtained for the additional risk factors and causal relationship between personal characteristics and traits to the chance of the Alzheimer’s development at some moment in life.

Among the findings were:

1. Those, who had revealed better linguistic abilities in early life, were less likely to have dementia later.

2. Those, who demonstrated set of positive emotions in early life, had greater longevity.

3. Low linguistic ability in early life was associated both with dementia in later life and less longevity.

4. Those with low serum folate levels were more likely to have Alzheimer's disease of other dementia.

5. There was no significant relationship found between dental amalgams (silver fillings) and dementia.

6. Those with brain infarcts had poorer cognitive function and a higher prevalence of dementia.

7. Dementia was unrecognized by nursing staff in a number of cases.

8. Higher education in early life was associated with less cognitive decline in later life.

The study has confirmed, for example, that a history of stroke and head trauma can boost your chances of coming down with debilitating symptoms of Alzheimer's later in life; and that a college education and an active intellectual life, on the other hand, may actually protect you from the effects of the disease.

One of the most surprising results of the Nun Study, however, is the discovery that the way we express ourselves in language, even at an early age, can foretell how long we'll live and how vulnerable we'll be to Alzheimer's decades down the line. After analyzing short autobiographies of almost 200 nuns, written when they first took holy orders, he found that the sisters who had expressed the most positive emotions in their writing and who expressed the better linguistic abilities as girls ended up living longest, and that those on the road to Alzheimer's expressed fewer and fewer positive emotions as their mental functions declined.

So, the study found that low idea density shown in the writings of the young women was strongly linked with low cognitive test scores and the presence of Alzheimer's disease in late life. For example, the nuns with low idea density scores were 30 times more likely to do poorly on a standard measure of cognitive function, the Mini-Mental State Exam, than those with more complex writings. An even more dramatic difference was observed when cognitive ability and characteristics of brain tissue were compared in the nuns who died. Neurofibrillary tangles of Alzheimer's disease appeared in about 90 percent of those nuns who had low linguistic ability in early life.

Among other findings there are some, which still do not have the valid scientific explanation, as why there is not always the direct correlation between the medical evidence for the Alzheimer’s disease appearance in the brain and the actual behavioral symptoms doctors can see on these patients.

"Most of the brains neatly fit our expectations, with little or no evidence of disease in a tack-sharp sister and abundant damage seen in a sister who had dementia," Dr. Snowdon wrote. "But sometimes (Dr. Bill) Markesbery (the neurologist who did the autopsies) finds little evidence of Alzheimer's in a sister who had the classic symptoms of the disease. And sometimes brains from other sisters who appeared mentally intact when alive show extensive evidence of the disease."

This surprising information wasn't a set-up by the researchers.  In fact, Dr. Snowdon noted that Dr. Markesbery was not informed prior to conducting the autopsy about the mental status of that particular sister. After the autopsy, Dr. Markesbery met with Dr. Snowdon and the study's neuropsychologist, Dr. Kathryn Riley, to compare notes.

In one case - that of Sister Maria - Dr. Markesbery found that the nun had some plaques and tangles, but the number was not large. The nun's brain itself weighed within the normal range (most Alzheimer's brains have lower weights). Furthermore, the sister's brain rated Stage II on the Braak scale. (The Braak scale defines six distinct stages of the disease based on an autopsy. Stage 0 indicates the general absence of tangles. Stages 1-VI described the increasing range of the number and spread of the tangles throughout the brain.)

Following Dr. Markesbery's report, Dr. Riley shared Sister Maria's scores on three evaluations conducted prior to her death. These evaluations showed that Sister Maria had suffered progressive loss of her mental, physical and social functions in a way that was consistent with Alzheimer's disease.

Yet the reverse can happen as well. For instance, Dr. Markesbery's autopsy of Sister Bernadette's brain yielded the findings that she had Braak Stage VI, which indicates the most severe presence of Alzheimer's. However, Dr. Riley's report on the cognitive evaluations conducted in the years prior to Sister Bernadette's death showed that the nun was mentally sharp.

 "The Nun Study's real eye-opening findings...are the ones that add to the evidence that Alzheimer's is not a yes/no disease," Dr. Snowdon wrote. "Rather it is a process - one that evolves over decades and interacts with many other factors." Using the data from the Nun's Study, Dr. Snowdon pointed out, "Of sisters in stages I or II, only 22 percent had evidence of dementia. For stages III and IV, that jumped to 43 percent. And by stages V and VI, 70 percent of the sisters had dementia."

While there is no magical cure for Alzheimer’s so far, the findings from Nun Study may give a hope that even you may not be able to eliminate the negative neurochemical changes in your brain, you still can fight the symptoms actual appearance by filling your life with regular physical and mental exercises, healthy diet, lowering stress, attempting to happy and present, etc. This way, you can be proactive in altering how this disease may affect you at some point, if you have predisposition, and follow in Sister Bernadette's footsteps, living a long and vital life.

Sources and Additional Information:

http://www.suite101.com/article.cfm/alzheimers_disease/90363

http://www.healthstudies.umn.edu/nunstudy/faq.jsp

http://defoore.com/theNunStudy.htm

http://www.nia.nih.gov/Alzheimers/ResearchInformation/NewsReleases/Archives/PR1996/PR19960220nunstudy.htm

http://www.healthcentral.com/alzheimers/c/42/88723/nun-contradictions/

Link between smell deterioration and Alzheimer's Disease

Alzheimer's disease, the plague of human civilization, appears to have strong connection with sense of smell. Russian scientists found out that parosmia or olfaction disorder can be the first sign of this terminal disease. Researchers from the Institute of Cell Biophysics developed a model, which allows early diagnostics and prevention of Alzheimer's disease.

Olfactory disorder: A loss in the ability to smell or a change in the way odors are perceived. Reduction of the sense of smell is termed hyposmia. Total inability to detect odors is termed anosmia. As for changes in the perception of odors, some people notice that familiar odors become distorted. Or, an odor that usually smells pleasant instead smells foul. Still other people may perceive a smell that is not present.

Modern neurology has several important parts, and one of them is studying factors, causing neurodegeneration in brain. Alzheimer's disease is a bright example of neurodegeneration. This pathological process leads to total degradation of personality and memory loss in elderly people, as well as deterioration of spatial orientation. Modern medicine has over 10 theories, trying to explain the nature of this disease. Most popular theory links beginning of Alzheimer's disease with accumulation of a specific protein in brain. This protein, called amyloid beta peptide, is toxic for neurons – nervous cells.

This protein does exist in an organism under normal conditions, but its concentration is extremely low. When the disease starts, this protein accumulates in brain in the form of plaques, similar to those of atherosclerosis. Initial stage of Alzheimer's disease is often notable for olfaction disorders. Russian scientists decided to find out whether link between smell deterioration and neurodegeneration existed. Alzheimer's disease progresses very slowly, thus a reliable model of this disease would have been a great help to medics.

Researchers investigated consequences, appearing in animals, which olfactory bulbs were removed, and found that defects in olfactory system formed same symptoms as Alzheimer's disease. Scientists explain this effect with direct links of olfactory system with a hippocampus, an important part of brain. The fact that hippocampus deterioration is a central stage in Alzheimer's disease development, is beyond question. Experiments revealed that when a link between an olfactory bulb and hippocampus is broken, biochemical shifts appear, which increase the amount of beta amyloid plaques, thus promoting the disease.

Olfaction disorder is the very first sign of Alzheimer's disease. The model, created by Russian scientists, allows not only diagnosing this disease, but also performing search of new pharmaceuticals. Now medics can examine olfaction system of a patient, while there are no visible signs of Alzheimer's disease, and advise some preventive measures. At this stage a patient has about 3-4 years to cope with his disease.

The results, obtained by Russian scientists comply with previous researches outcomes. There have been scattered reports of evidence suggesting that a diminished sense of smell is associated with Alzheimer’s disease. In 1987, Rezek reported on olfactory deficits as a neurological sign in dementia of the Alzheimer type. Talamo and his group examined changes in olfactory neurons in patients with Alzheimer’s disease. They indicated that there were histopathological changes in olfactory epithelium. In 1991, Hyman and colleagues suggested that neuroanatomical and neurochemical changes related to Alzheimer’s disease occur in the olfactory bulb of the brain, confirming prior studies. Other areas that exhibited degeneration included the anterior olfactory nucleus, the olfactory tubercle, the uncus and the subiculum. These studies could be challenged on methodological grounds, but still carry some weight.

Finally, researchers at the University of Pennsylvania School of Medicine have linked smell loss in mice with excessive levels of a key protein associated with Alzheimer's and Parkinson's disease in 2004.

"The loss of smell – or olfactory dysfunction – has been known for more than a decade as an early sign of several neurodegenerative diseases, but we have never been able to link it to a pathological entity that is measurable over time," said Richard Doty, PhD, Professor and Director of Penn's Smell and Taste Center, who is also the team leader of the study. "By tying decrements in the ability to smell to the presence of key disease proteins, such as tau, we may well be able to assess the degree of progression of selected elements of Alzheimer's disease and related disorders by scores on quantitative smell tests."

Sources and Additional Information:
http://www.russia-ic.com/education_science/science/breakthrough/930/
http://www.medterms.com/script/main/art.asp?articlekey=39215
http://www.sciencedaily.com/releases/2004/03/040312090410.htm
http://www.therubins.com/alzheim/alzpst10.htm

Can Coffee Lower and Reverse Alzheimer’s Negative Effects?

A daily dose of caffeine blocks the disruptive effects of high cholesterol that scientists have linked to Alzheimer's disease. A study in the open access publication, Journal of Neuroinflammation revealed that caffeine equivalent to just one cup of coffee a day could protect the blood-brain barrier (BBB) from damage that occurred with a high-fat diet.

The BBB protects the central nervous system from the rest of the body's circulation, providing the brain with its own regulated microenvironment. Previous studies have shown that high levels of cholesterol break down the BBB which can then no longer protect the central nervous system from the damage caused by blood borne contamination. BBB leakage occurs in a variety of neurological disorders such as Alzheimer's disease.

University of the University of North Dakota School of Medicine and Health Sciences Research (2006)

In this study, researchers from the University of North Dakota School of Medicine and Health Sciences gave rabbits 3 mg caffeine each day - the equivalent of a daily cup of coffee for an average-sized person. The rabbits were fed a cholesterol-enriched diet during this time.

After 12 weeks a number of laboratory tests showed that the BBB was significantly more intact in rabbits receiving a daily dose of caffeine.

"Caffeine appears to block several of the disruptive effects of cholesterol that make the blood-brain barrier leaky," says Jonathan Geiger, University of North Dakota School of Medicine and Health Sciences. "High levels of cholesterol are a risk factor for Alzheimer's disease, perhaps by compromising the protective nature of the blood-brain barrier. For the first time we have shown that chronic ingestion of caffeine protects the BBB from cholesterol-induced leakage."

Caffeine appears to protect BBB breakdown by maintaining the expression levels of tight junction proteins. These proteins bind the cells of the BBB tightly to each other to stop unwanted molecules crossing into the central nervous system.

The findings confirm and extend results from other studies showing that caffeine intake protects against memory loss in aging and in Alzheimer's disease.

"Caffeine is a safe and readily available drug and its ability to stabilize the blood-brain barrier means it could have an important part to play in therapies against neurological disorders," says Geiger. 

Research in France (2007)

The researchers, studying more than 7,000 older men and women living in three cities in France, found that women age 65 and older who drank more than three cups of coffee scored better on tests that measure thinking and memory skills than women who drank a cup or less of coffee or tea a day.

The results held up even after researchers adjusted for other factors that could affect memory, such as age, education, disability, medications, depression, high blood pressure, heart disease, and other chronic illnesses. The men in the study, however, did not show the same benefits from drinking coffee as the women.

“Caffeine is a psycho-stimulant which appears to reduce cognitive decline in women,” said study author Dr. Karen Ritchie of INSERM, the French National Institute for Health and Medical Research, in Montpellier, France. “While we have some ideas as to how this works biologically, we need to have a better understanding of how caffeine affects the brain before we can start promoting caffeine intake as a way to reduce cognitive decline.”

“But the results are interesting,” Ritchie continues. “Caffeine use is already widespread, it has fewer side effects than other treatments for cognitive decline, and it requires a relatively small amount for a beneficial effect.”

At the start of the study, all the seniors were evaluated for thinking and memory function. None had Alzheimer’s disease or other signs of serious memory loss, such as mild cognitive impairment. They were then evaluated over the following four years.

Compared to women who drank one cup or less of coffee per day, those who drank over three cups were less likely to show as much decline in memory. Moreover, the benefits increased with age. Coffee drinkers were 30 percent less likely to score poorly on memory tests at age 65 than those who drank little or no coffee. That figure increased to 70 percent in those older than 80.

Women who drank two or three cups of coffee a day did not show any notable boosts in memory.

The heavy coffee drinkers scored particularly well in tests that measured verbal recall, such as the ability to remember particulars of a story. They did slightly better in tests that measure visual and spatial memory.

Caffeine drinkers, however, did not seem to have lower rates of Alzheimer’s disease. “We really need a longer study to look at whether caffeine prevents dementia; it might be that caffeine could slow the dementia process rather than preventing it,” said Dr. Ritchie.

The researchers aren’t sure why caffeine didn’t show the same result in men. “Women may be more sensitive to the effects of caffeine,” Dr. Ritchie said. “Their bodies may react differently to the stimulant, or they may metabolize caffeine differently.”

Florida Byrd Alzheimer's Institute Study (2007)

According to research published in the Journal of Neuroscience, caffeine intake not only appears to protect against Alzheimer's but may actually help those who already have the disease.

Researchers at the Byrd Alzheimer's Institute in Florida have reported that five cups of coffee a day could protect humans in the same way that the caffeine equivalent appears to have in the study of mice.

In a controlled study experiment using Alzheimer's mice, one group of mice had caffeine added to their drinking water. The memory of mice, who drank the caffeinated water, was roughly similar to mice to had no Alzheimer's. Researchers also found that levels of beta-amyloid proteins reduced in mice, who drank caffeine. Beta-amyloid proteins aggregate into plaques within the brain and are present in the brains of people with Alzheimer's disease.

Some interesting results were also obtained when researchers gave caffeine to aged Alzheimer's mice who already had high levels of beta-amyloid protein in their brains. It was discovered that caffeine reduced the levels of beta-amyloid already present in the brain. This could suggest that coffee drinking is beneficial in people with Alzheimer's; for the time being this is speculation.

The therapeutic effects of caffeine over the long-term have been noted in relation to reduced risk of type 2 diabetes, Parkinson's disease, cirrhosis of the liver, cancer of the liver, colorectal cancer and suicide. Although caffeine has been suspected of causing high blood pressure the association appears stronger when caffeine is consumed via soft drinks.

University of South Florida Study (2009)

The 55 mice used in the University of South Florida study had been bred to develop symptoms of Alzheimer's disease.

First the researchers used behavioural tests to confirm the mice were exhibiting signs of memory impairment when they were aged 18 to 19 months, the equivalent to humans being about 70.

Then they gave half the mice caffeine in their drinking water. The rest were given plain water.

The mice were given the equivalent of five 8 oz (227 grams) cups of coffee a day - about 500 milligrams of caffeine. The researchers say this is the same as is found in two cups of "specialty" coffees such as lattes or cappuccinos from coffee shops, 14 cups of tea, or 20 soft drinks.

When the mice were tested again after two months, those who were given the caffeine performed much better on tests measuring their memory and thinking skills and performed as well as mice of the same age without dementia.

Those drinking plain water continued to do poorly on the tests.

In addition, the brains of the mice given caffeine showed nearly a 50% reduction in levels of the beta amyloid protein, which forms destructive clumps in the brains of dementia patients. Further tests suggested caffeine affects the production of both the enzymes needed to produce beta amyloid.

The researchers also suggest that caffeine suppresses inflammatory changes in the brain that lead to an overabundance of the protein. Earlier research by the same team had shown younger mice, who had also been bred to develop Alzheimer's but who were given caffeine in their early adulthood, were protected against the onset of memory problems.

Dr Gary Arendash, who led the latest study, told the BBC: "The results are particularly exciting in that a reversal of pre-existing memory impairment is more difficult to achieve.

"They provide evidence that caffeine could be a viable 'treatment' for established Alzheimer's disease and not simply a protective strategy. "That's important because caffeine is a safe drug for most people, it easily enters the brain, and it appears to directly affect the disease process."

The team now hopes to begin human trials of caffeine to see if the mouse findings are replicated in people. They do not know if a lower amount of caffeine would be as effective, but said most people could safely consume the 500 milligrams per day.

However they said people with high blood pressure, and pregnant women, should limit their daily caffeine intake.

Rebecca Wood, chief executive of the Alzheimer's Research Trust, said: "In this study on mice with symptoms of Alzheimer's, researchers found that caffeine boosted their memory. We need to do more research to find out whether this effect will be seen in people. "It is too early to say whether drinking coffee or taking caffeine supplements will help people with Alzheimer's.

Conclusion

The results, produced in the several reviewed researches are mostly promising, but just because caffeine treats memory loss in mice doesn't mean it's necessarily good for humans, says Eric Hall, president and CEO of the Alzheimer's Foundation of America.

"A human being's brain processes very differently than a mouse's brain, so the public has to be cautious," Hall said. "This is a first step, but there are a lot more steps to be done. We are hopeful, but many failed clinical trials can testify to the fact that what works in mice doesn't always work in humans."

Note that some caution with coffee drinking is still advised. Caffeine is a drug, and can be associated with increased blood pressure, increased heart rate, jitteriness, palpitations and dehydration. "For people who have irregular heart beats, hypertension, women who are pregnant or those who are sensitive to the effects of caffeine, coffee, tea or soda should be consumed in moderation."  These people should also discuss caffeine consumption with their health care provider.

Sources and Additional Information:

http://www.medicalnewstoday.com/articles/102703.php

http://www.alzinfo.org/newsarticle/templates/newstemplate.asp?articleid=239&zoneid=10

http://alzheimers.about.com/od/research/a/Coffee_Alz.htm

http://news.bbc.co.uk/2/hi/health/8132122.stm

http://www.nydailynews.com/lifestyle/health/2009/07/06/2009-07-06_coffee_may_help_treat_memory_loss_a_major_symptom_of_al.html

http://www.cbsnews.com/stories/2009/07/06/earlyshow/main5136373.shtml