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.
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
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.
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
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, inMontpellier , France
“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.”
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
“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.”
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
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.
The 55 mice used in the University of South Florida
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.
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