Caffeine reduces risk of Alzheimer's

TAMPA, Fla.—If you think your daily cups of coffee only provide you with alertness after you wake up or during the day, think again. Long-term intake of caffeine, the major constituent in coffee and tea, has been shown to reduce the risk of Alzheimer’s in mice that develop the disease.

In a study just published online in the journal Neuroscience, researchers at the Byrd Alzheimer’s Institute in Tampa, Fl., are reporting that caffeine intake equivalent to five cups of coffee a day in humans protects Alzheimer’s mice against otherwise certain memory impairment and reduces Alzheimer’s pathology in their brains.

An earlier study in humans hinted that caffeine was protective against Alzheimer’s disease by showing that Alzheimer’s patients consumed markedly less caffeine during the 20 years preceding disease diagnosis compared with age-matched individuals without Alzheimer’s disease.

“We wanted to test the ability of dietary caffeine intake to protect against Alzheimer’s disease in a highly-controlled study in Alzheimer’s mice where the only variable that was different between groups was whether caffeine was in their drinking water or not,” says Dr. Gary Arendash, Ph.D., lead researcher in the study. “We were surprised to find that Alzheimer’s mice given caffeine in their drinking water throughout adult life performed much better than Alzheimer’s mice not given caffeine and very similar to normal mice without the disease,” adds Arendash.

Not only was the memory of Alzheimer’s mice protected by the human equivalent of five cups of coffee per day (500 mg/day), but levels of an abnormal brain protein that most researchers believe causes the disease were reduced. This abnormal protein, called beta-amyloid, is formed by the actions of two enzymes on a much larger protein called APP, which extends through the cell membrane of brain cells. The two enzymes (BACE and PS1) cut APP in specific places, resulting in beta-amyloid formation. Once formed, beta-amyloid molecules aggregate into “plaques” within the brain, causing death and dysfunction of cells, especially in brain areas important for learning and memory. The researchers found that caffeine reduces the level of both BACE and PS1 enzymes, thus resulting in much less of the dangerous beta-amyloid protein.

Even when the researchers administered caffeine to aged Alzheimer’s mice that already had high levels of beta-amyloid in their brains, caffeine intake resulted in lower beta-amyloid levels. This finding suggests that even individuals who already have the disease could benefit from a moderate daily intake of caffeine.

“Some of the current therapeutics being developed against Alzheimer’s disease involve synthetic compounds capable of suppressing either BACE or PS1 enzymes in the brain,” Dr. Arendash says. “It appears we have found a totally natural and very safe dietary compound for most of us, namely caffeine, that suppresses both of these enzymes. This is the most likely way that caffeine is protecting our mice against Alzheimer’s disease, although there are several other possible mechanisms,” adds Arendash.

The researchers began giving Alzheimer’s mice caffeine in their drinking water at 4 months of age and continued treatment through 9 months of age—an age at which beta-amyloid levels are rapidly increasing in Alzheimer’s mice. During the final month of caffeine treatment, mice were tested in a variety of tasks involving learning, memory and recognition. Across multiple behavioral measures, the Alzheimer’s mice given caffeine performed much better than those that had been given given normal drinking water. Long-term dietary caffeine protected many aspects of cognition in these mice, not simply one aspect.

For an 8-ounce serving, drip coffee typically contains 100 mg caffeine, tea contains about 35 mg caffeine, and soft drinks contain 25 mg caffeine. To attain the 500 mg caffeine per day equivalent in humans that the researchers found to be protective in Alzheimer’s mice, only five cups of coffee would be required. Since some coffees, especially from specialty shops, contain considerably more than 100 mg caffeine per 8-ounce cup, fewer than five cups may be needed.

“The results of our study add Alzheimer’s disease to a growing list of age-related diseases where caffeine or coffee appear to reduce the risk,” says Dr. Arendash.

Long-term intake of caffeine and/or coffee has been linked to reduced risk of type 2 diabetes, Parkinson’s disease, liver cirrhosis, liver cancer, suicide risk and colorectal cancer. Although caffeine has been suspected of causing hypertension, a recent study showed that there is no association between caffeine consumption “in coffee” and blood pressure. By contrast, caffeine in sugared and diet soft drinks did increase the risk of hypertension.

“Aside from its rich source of caffeine, coffee is the primary dietary source of antioxidants for Americans, which may be why drinking coffee does not seem to increase risk of hypertension,” says Dr. Arendash.

The study involved several laboratories and universities collaborating with the Byrd Institute. Other collaborators in the study include Dr. Jun Tan, Ph.D., of the University of South Florida College of Medicine and Dr. Ed Jackson, Ph.D., of the University of Pittsburgh School of Medicine.

Alzheimer’s disease is a neurodegenerative disease that results in the loss of brain cells and their connections. Signs of the disease usually become evident after 65 years of age, initially as a loss of short-term memory for events that occurred a few minutes earlier. Over the disease’s time course of two to 20 years, cognitive impairment expands to involve long-term memory and language skills. Eventually, all aspects of intellect are lost. Alzheimer’s disease afflicts 4.5 million Americans and costs the U.S. economy $100 billion a year. Ten percent of people 65 or older and half of those 85 or older are victims of the disease. With the aging baby boomer generation, the number of Americans with Alzheimer’s disease will more than double by 2050, and the costs to society will balloon as well.

Aside from consuming caffeine, Americans can take other precautions to decrease their risk for Alzheimer’s or delay the disease’s onset. These include:

Keeping cognitively active, exercising your brain;

Eating a low-fat diet rich in antioxidants; and

Keeping weight, blood sugar, blood pressure and cholesterol levels in check.

Dr. Arendash is a research professor at the Byrd Alzheimer’s Institute and director of the Institute’s Mouse Core. He is also a full professor in the College of Arts and Sciences, University of South Florida. Dr. Arendash has been active in neuroscience research for more than 25 years, having spent the last eight years using Alzheimer’s mice to explore prevention and treatment strategies against the disease.

The mission of the Byrd Alzheimer’s Institute is to prevent and cure Alzheimer’s disease. Created in 2002 by the Florida Legislature, the Institute is dedicated to supporting and coordinating the tremendous research, expertise and creative vision of scientific professionals all over Florida.

The National Institutes of Health designated the Byrd Institute and the University of South Florida part of the Alzheimer’s Disease Research Center in Florida, generating more than $7 million in research money. This designation is the first ever for the state of Florida. There are only 32 of these centers in the country, and Florida is one of only 21 states with centers that have earned the designation. Learn more at

From the Sept. 27-Oct.3, 2006, issue

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