Caffeine
against Alzheimer's disease
As part of a German-French research
project, a team led by Dr. Christa E. Müller from the University of Bonn and
Dr. David Blum from the University of Lille was able to demonstrate for the
first time that caffeine has a positive effect on tau deposits in Alzheimer's
disease. The two-years project was supported with 30,000 Euro from the
non-profit Alzheimer Forschung Initiative e.V. (AFI) and with 50,000 Euro from
the French Partner organization LECMA. The initial results were published in
the online edition of the journal "Neurobiology
of Aging."
Tau deposits, along with
beta-amyloid plaques, are among the characteristic features of Alzheimer's
disease. These protein deposits disrupt the communication of the nerve cells in
the brain and contribute to their degeneration. Despite intensive research
there is no drug available to date which can prevent this detrimental process.
Based on the results of Prof. Dr. Christa Müller from the University of Bonn,
Dr. David Blum and their team, a new class of drugs may now be developed for
the treatment of Alzheimer's disease.
Caffeine, an adenosine receptor
antagonist, blocks various receptors in the brain which are activated by
adenosine. Initial results of the team of researchers had already indicated
that the blockade of the adenosine receptor subtype A2A in particular could
play an important role. Initially, Prof. Müller and her colleagues developed an
A2A antagonist in ultrapure and water-soluble form (designated MSX-3). This
compound had fewer adverse effects than caffeine since it only blocks only the
A2A adenosine receptor subtype, and at the same time it is significantly more
effective. Over several weeks, the researchers then treated genetically altered
mice with the A2A antagonist. The mice had an altered tau protein which,
without therapy, leads to the early development of Alzheimer's symptoms.
In comparison to a control group
which only received a placebo, the treated animals achieved significantly
better results on memory tests. The A2A antagonist displayed positive effects
in particular on spatial memory. Also, an amelioration of the pathogenic
processes was demonstrated in the hippocampus, which is the site of memory in
rodents.
"We have taken a good step
forward," says Prof. Müller. "The results of the study are truly
promising, since we were able to show for the first time that A2A adenosine
receptor antagonists actually have very positive effects in an animal model
simulating hallmark characteristics and progression of the disease. And the
adverse effects are minor."
The researchers now want to test the
A2A antagonist in additional animal models. If the results are positive, a
clinical study may follow. "Patience is required until A2A adenosine
receptor antagonists are approved as new therapeutic agents for Alzheimer's
disease. But I am optimistic that clinical studies will be performed,"
says Prof. Müller.
Caffeine Enhances Memory
The consumption
of caffeine is the energy boost of choice for millions to wake up or stay up.
Now, however, researchers at the Johns Hopkins University have found another
use for the stimulant: memory enhancer.
Michael Yassa,
assistant professor of psychological and brain sciences in the Krieger School
of Arts and Sciences at Johns Hopkins, and his team of scientists found that
caffeine has a positive effect on long-term memory in humans. Their research,
published by the journal Nature Neuroscience, shows that caffeine enhances
certain memories at least up to 24 hours after it is consumed.
"We've
always known that caffeine has cognitive-enhancing effects, but its particular
effects on strengthening memories and making them resistant to forgetting has
never been examined in detail in humans," said Yassa, senior author of the
paper. "We report for the first time a specific effect of caffeine on
reducing forgetting over 24 hours."
The Johns
Hopkins researchers conducted a double-blind trial; which participants who did
not regularly eat or drink caffeinated products received either a placebo or a
200-milligram caffeine tablet five minutes after studying a series of images.
Salivary samples were taken from the participants before they took the tablets
to measure their caffeine levels. Samples were taken again one, three and 24
hours afterwards.
The next day,
both groups were tested on their ability to recognize images from the previous
day's study session. On the test, some of the visuals were the same as from the
day before, some were new additions and some were similar but not the same as
the items previously viewed. More members of the caffeine group were able to
correctly identify the new images as "similar" to previously viewed
images versus erroneously citing them as the same.
The brain's
ability to recognize the difference between two similar but not identical
items, called pattern separation, reflects a deeper level of memory retention,
the researchers said.
"If we used
a standard recognition memory task without these tricky similar items, we would
have found no effect of caffeine," Yassa said. "However, using these
items requires the brain to make a more difficult discrimination -- what we
call pattern separation, which seems to be the process that is enhanced by
caffeine in our case."
The
memory center in the human brain is the hippocampus, a seahorse-shaped area in
the medial temporal lobe of the brain. The hippocampus is the switchbox for all
short-term and long-term memories. Most research done on memory -- the effects
of concussions in athletics to war-related head injuries to dementia in the
aging population -- are focused on this area of the brain.
Until now,
caffeine's effects on long-term memory had not been examined in detail. Of the
few studies done, the general consensus was that caffeine has little or no
effect on long-term memory retention.
The research is
different from prior experiments because the subjects took the caffeine tablets
only after they had viewed and attempted to memorize the images.
"Almost all
prior studies administered caffeine before the study session, so if there is an
enhancement, it's not clear if it's due to caffeine's effects on attention,
vigilance, focus or other factors. By administering caffeine after the
experiment, we rule out all of these effects and make sure that if there is an
enhancement, it's due to memory and nothing else," said Yassa.
According to the
U.S. Food and Drug Administration, 90 percent of people worldwide consume
caffeine in one form or another. In the United States, 80 percent of adults
consume caffeine every day. The average adult has an intake of about 200
milligrams -- the same amount used in the Yassa study -- or roughly one strong
cup of coffee or two small cups of coffee per day.
Yassa's team
completed the research at Johns Hopkins before his lab moved to the University
of California-Irvine at the start of this year.
"The next
step for us is to figure out the brain mechanisms underlying this
enhancement," he said. "We can use brain-imaging techniques to
address these questions. We also know that caffeine is associated with healthy
longevity and may have some protective effects from cognitive decline like
Alzheimer's disease. These are certainly important questions for the
future."
High blood caffeine levels linked to avoidance of Alzheimer's disease
Those cups of
coffee that you drink every day to keep alert appear to have an extra perk –
especially if you're an older adult. A recent study monitoring the memory and
thinking processes of people older than 65 found that all those with higher
blood caffeine levels avoided the onset of Alzheimer's disease in the two-to-four
years of study follow-up. Moreover, coffee appeared to be the major or only
source of caffeine for these individuals.
Researchers from
the University of South Florida (www.usf.edu) and the University of Miami
(www.miami.edu)say the case control study provides the first direct evidence
that caffeine/coffee intake is associated with a reduced risk of dementia or
delayed onset. Their findings appeared in the Journal of Alzheimer's Disease, published by IOS Press. The
collaborative study involved 124 people, ages 65 to 88, in Tampa and Miami.
"These
intriguing results suggest that older adults with mild memory impairment who
drink moderate levels of coffee -- about 3 cups a day -- will not convert to
Alzheimer's disease -- or at least will experience a substantial delay before
converting to Alzheimer's," said study lead author Dr. Chuanhai Cao, a
neuroscientist at the USF College of Pharmacy and the USF Health Byrd
Alzheimer's Institute "The results from this study, along with our earlier
studies in Alzheimer's mice, are very consistent in indicating that moderate
daily caffeine/coffee intake throughout adulthood should appreciably protect
against Alzheimer's disease later in life."
The study shows
this protection probably occurs even in older people with early signs of the
disease, called mild cognitive impairment, or MCI. Patients with MCI already
experience some short-term memory loss and initial Alzheimer's pathology in
their brains. Each year, about 15 percent of MCI patients progress to
full-blown Alzheimer's disease. The researchers focused on study participants
with MCI, because many were destined to develop Alzheimer's within a few years.
Blood caffeine
levels at the study's onset were substantially lower (51 percent less) in
participants diagnosed with MCI who progressed to dementia during the
two-to-four year follow-up than in those whose mild cognitive impairment
remained stable over the same period.
No one with MCI
who later developed Alzheimer's had initial blood caffeine levels above a
critical level of 1200 ng/ml – equivalent to drinking several cups of coffee a
few hours before the blood sample was drawn. In contrast, many with stable MCI
had blood caffeine levels higher than this critical level.
"We found
that 100 percent of the MCI patients with plasma caffeine levels above the
critical level experienced no conversion to Alzheimer's disease during the
two-to-four year follow-up period," said study co-author Dr. Gary
Arendash.
The researchers
believe higher blood caffeine levels indicate habitually higher caffeine
intake, most probably through coffee. Caffeinated coffee appeared to be the
main, if not exclusive, source of caffeine in the memory-protected MCI
patients, because they had the same profile of blood immune markers as
Alzheimer's mice given caffeinated coffee. Alzheimer's mice given caffeine
alone or decaffeinated coffee had a very different immune marker profile.
Since 2006,
USF's Dr. Cao and Dr. Arendash have published several studies investigating the
effects of caffeine/coffee administered to Alzheimer's mice. Most recently,
they reported that caffeine interacts with a yet unidentified component of
coffee to boost blood levels of a critical growth factor that seems to fight
off the Alzheimer's disease process.
"We are not
saying that moderate coffee consumption will completely protect people from
Alzheimer's disease," Dr. Cao cautioned. "However, we firmly believe
that moderate coffee consumption can appreciably reduce your risk of
Alzheimer's or delay its onset."
Alzheimer's pathology
is a process in which plaques and tangles accumulate in the brain, killing
nerve cells, destroying neural connections, and ultimately leading to
progressive and irreversible memory loss. Since the neurodegenerative disease
starts one or two decades before cognitive decline becomes apparent, the study
authors point out, any intervention to cut the risk of Alzheimer's should
ideally begin that far in advance of symptoms.
"Moderate
daily consumption of caffeinated coffee appears to be the best dietary option
for long-term protection against Alzheimer's memory loss," Dr. Arendash
said. "Coffee is inexpensive, readily available, easily gets into the
brain, and has few side-effects for most of us. Moreover, our studies show that
caffeine and coffee appear to directly attack the Alzheimer's disease
process."
In addition to
Alzheimer's disease, moderate caffeine/coffee intake appears to reduce the risk
of several other diseases of aging, including Parkinson's disease, stroke, Type
II diabetes, and breast cancer. However, supporting studies for these benefits
have all been observational (uncontrolled), and controlled clinical trials are
needed to definitively demonstrate therapeutic value.
A study tracking
the health and coffee consumption of more than 400,000 older adults for 13
years, and published earlier this year in the New England Journal of Medicine, found that coffee drinkers reduced
their risk of dying from heart disease, lung disease, pneumonia, stroke,
diabetes, infections, and even injuries and accidents.
With new
Alzheimer's diagnostic guidelines encompassing the full continuum of the
disease, approximately 10 million Americans now fall within one of three
developmental stages of Alzheimer's disease -- Alzheimer's disease brain
pathology only, MCI, or diagnosed Alzheimer's disease. That number is expected
to climb even higher as the baby-boomer generation continues to enter older
age, unless an effective and proven preventive measure is identified.
"If we
could conduct a large cohort study to look into the mechanisms of how and why
coffee and caffeine can delay or prevent Alzheimer's disease, it might result
in billions of dollars in savings each year in addition to improved quality of
life," Dr. Cao said.
Coffee could protect against
Alzheimer's disease
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.
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 stabilise the blood-brain
barrier means it could have an important part to play in therapies against
neurological disorders,” says Geiger.
Caffeine may block
inflammation linked to mild cognitive impairment
Recent studies have linked caffeine consumption to a reduced
risk of Alzheimer's disease, and a new University of Illinois study may be able
to explain how this happens.
"We have discovered a novel signal that activates the
brain-based inflammation associated with neurodegenerative diseases, and
caffeine appears to block its activity. This discovery may eventually lead to
drugs that could reverse or inhibit mild cognitive impairment," said
Gregory Freund, a professor in the U of I's College of Medicine and a member of
the U of I's Division of Nutritional Sciences.
Freund's team examined the effects of caffeine on memory
formation in two groups of mice—one group given caffeine, the other receiving
none. The two groups were then exposed to hypoxia, simulating what happens in
the brain during an interruption of breathing or blood flow, and then allowed
to recover.
The caffeine-treated mice recovered their ability to form a
new memory 33 percent faster than the non-caffeine-treated mice. In fact,
caffeine had the same anti-inflammatory effect as blocking IL-1 signaling. IL-1
is a critical player in the inflammation associated with many neurodegenerative
diseases, he said.
"It's not surprising that the insult to the brain that
the mice experienced would cause learning memory to be impaired. But how does
that occur?" he wondered.
The scientists noted that the hypoxic episode triggered the
release of adenosine by brain cells.
"Your cells are little powerhouses, and they run on a
fuel called ATP that's made up of molecules of adenosine. When there's damage
to a cell, adenosine is released," he said.
Just as gasoline leaking out of a tank poses a danger to
everything around it, adenosine leaking out of a cell poses a danger to its
environment, he noted.
The extracellular adenosine activates the enzyme caspase-1,
which triggers production of the cytokine IL-1β, a critical player in
inflammation, he said.
"But caffeine blocks all the activity of adenosine and
inhibits caspase-1 and the inflammation that comes with it, limiting damage to
the brain and protecting it from further injury," he added.
Caffeine's ability to block adenosine receptors has been
linked to cognitive improvement in certain neurodegenerative diseases and as a
protectant against Alzheimer's disease, he said.
"We feel that our foot is in the door now, and this
research may lead to a way to reverse early cognitive impairment in the brain.
We already have drugs that target certain adenosine receptors. Our work now is
to determine which receptor is the most important and use a specific antagonist
to that receptor," he said.
In women, caffeine may protect
memory
Caffeine may
help older women protect their thinking skills, according to a study published
in the August 7, 2007, issue of Neurology,
the medical journal of the American Academy of Neurology.
The study found
that women age 65 and older who drank more than three cups of coffee (or the
equivalent in tea) per day had less decline over time on tests of memory than
women who drank one cup or less of coffee or tea per day. The results held up
even after researchers adjusted for other factors that could affect memory
abilities, such as age, education, disability, depression, high blood pressure,
medications, cardiovascular disease, and other chronic illnesses.
“Caffeine is a
psychostimulant which appears to reduce cognitive decline in women,” said study
author Karen Ritchie,. “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 – caffeine use is already
widespread and it has fewer side effects than other treatments for cognitive
decline, and it requires a relatively small amount for a beneficial effect.”
The study
involved 7,000 people whose cognitive abilities and caffeine consumption were
evaluated over 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 being 30 percent less likely to have memory decline at age 65 and
rising to 70 percent less likely over age 80.
Caffeine
consumers did not seem to have lower rates of dementia. “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
Ritchie.
Ritchie said
researchers aren’t sure why caffeine didn’t show the same result in men. “Women
may be more sensitive to the effects of caffeine,” she said. “Their bodies may
react differently to the stimulant, or they may metabolize caffeine differently.”
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