New research from the US and Japan showed that giving the caffeine equivalent of five cups of coffee a day to aged mice with symptoms of Alzheimer’s reversed two signs of the disease: it reversed memory impairment and reduced the hallmark protein in the animals’ blood and brains.

The research was the work of scientists from the Florida Alzheimer’s Disease Research Center (ADRC) at the University of South Florida and colleagues from other research centers in the US and the Saitama Medical University in Japan. It is about to be published as two studies in the July issue of the Journal of Alzheimer’s Disease.

Both studies build on previous work by scientists at the Florida ADRC where they showed that giving caffeine to young adult mice genetically bred to have symptoms of Alzheimer’s prevented them developing the symptoms of the disease when they got old.

Lead author of the first paper and co-author of the second, Dr Gary Arendash, a neuroscientist with the Florida ADRC, told the media that these new findings show 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,” he added.

He and his colleagues hope to start trials in humans to see if caffeine helps people with mild cognitive impairment or early Alzheimer’s disease.

Dr Huntington Potter, director of the Florida ADRC said that they have already discovered that giving caffeine to elderly people who do not have dementia quickly affects their blood levels of beta-amyloid (a protein that forms stickly clumps of plaque in the brains of people with Alzheimer’s), which is what happened to the Alzheimer’s mice.

Potter said that:

“These are some of the most promising Alzheimer’s mouse experiments ever done showing that caffeine rapidly reduces beta amyloid protein in the blood, an effect that is mirrored in the brain, and this reduction is linked to cognitive benefit.”

He said they are now working on getting funding to replicate these findings in well designed clinical trials in humans.

The researchers were inspired to investigate caffeine’s potential as a treatment for Alzheimer’s when they spotted a Portuguese study that found people with Alzheimer’s had consumed less coffee in the previous 20 years of their lives than people who did not have the brain destroying disease.

Other studies have indicated that moderate caffeine intake may also protect against memory decline, but these were not properly controlled clinical trials, so Arendash and colleagues set up these controlled studies using genetically engineered mice so they could separate the effects of caffeine from other potential influencers like diet and physical activity.

For the study, he and his colleagues observed 55 transgenic mice that had been genetically altered to develop symptoms of Alzheimer’s disease (the mice were in effect genetically engineered to over-express the gene that makes beta-amyloid protein).

Behaviour tests showed the mice showed signs of memory impairment when they reached 18 to 19 months old (this is equivalent to 70 in human years). At this stage they were put in two groups: one received caffeine in their drinking water and the other did not, they just continued with plain water.

The caffeine group was given 500 mg of caffeine a day, the equivalent of five of regular cups of coffee, or 14 cups of tea, or 20 soft drinks.

After two months, the mice in the caffeine group did better on memory and thinking tests, and performed as well as mice of the same age without dementia, while the mice in the non-caffeine group continued to do poorly in the tests.

When Arendash and colleagues examined the brains of the mice they found that those of the caffeine group had nearly 50 per cent less beta-amyloid.

Because of what they have found in other experiments, Arendash and colleagues suggest that the memory is restored because caffeine appears to reduce both of the enzymes needed to produce beta-amyloid protein ( beta-secretase or BACE1, and presenilin 1 or PS1/g-secretase). Another reason could be that caffeine inhibits inflammation that causes too much beta-amyloid to be made, they said.

In another experiment they found that giving caffeine to non-dementia bred (ie normal) mice from young adulthood to old age did not boost their memory. Control mice that drank water without caffeine all their lives did as well in memory tests in old age as mice that had been given caffeine.

Arendash said this suggests that:

“Caffeine will not increase memory performance above normal levels.”

He said caffeine appeared to benefit only those mice bred to develop Alzheimer’s symptoms.

The researchers did not find out if less that 500 mg of caffeine a day would have the same effect. Although various bodies suggest that most people would be able to consume this amount every day with no ill effects, Arendash said people with high blood pressure and pregnant women should be careful to limit their caffeine intake.

Alzheimer’s disease affects nearly half of Americans over the age of 85, and together with other dementias it triples the healthcare costs for people over 65, according to figures from the Alzheimer’s Association.

If these findings can be replicated in larger, more robust trials in humans, the benefits will be enormous.

Related reading: Drinking Coffee: More Good Than Harm? (9 July 2012).

Written by: Catharine Paddock, PhD