Mice aren't humans. And caffeine jitters aren't for the faint of heart. But the caffeine connection raises intriguing possibilities for treating Alzheimer's disease.
USF scientists "were able to look both at the idea of treatment — giving caffeine to animals that have already developed pathology — as well as prevention,'' said Neil Buckholtz, chief of the dementias of aging branch of the National Institute on Aging. "It's really interesting.''
So should you binge on latte or invest in Starbucks?
No way, Buckholtz and others cautioned.
"Lots of things have proven effective in mouse models but very few have been tested in humans,'' he said. "That's the gold standard, to see how this translates to humans.''
The caffeine study, described in today's online version of the Journal of Alzheimer's Disease, was performed on mice genetically engineered to develop high levels of beta-amyloid, a protein associated with Alzheimer's in human brains.
Such mice typically start showing cognitive decline and elevated beta-amyloid levels by 8 or 9 months of age. As they grow older, they also develop sticky clumps of amyloid plaque in their brains, another sign of human Alzheimer's.
Three years ago, the USF group showed that putting the mice on a high-caffeine diet soon after birth seems to prevent or delay these symptoms.
The latest experiments were aimed at treatment.
The mice received no caffeine until they were 18 to 19 months old, the human equivalent of about 70.
By then, the mice had progressed well into their dementia. Beta-amyloid levels were high, protein clumps had developed in their brains, and they performed poorly on memory tests.
For four or five weeks, some of the mice received pure caffeine in their drinking water, equivalent to 500 milligrams a day in an average human. That's what you would get in about five 8-ounce cups of regular coffee or 14 12-ounce cans of Coke Classic.
Control mice drank straight water.
Then all the mice went swimming.
Many bad turns
In water mazes, mice swim around until they discover a comforting underwater platform that allows them to stand up and rest. Researchers return them to the water and watch how quickly they navigate their way back to the platform.
Normal mice with good memories find the platform without too many bad turns. A demented mouse struggles to learn.
In the USF study, demented mice fed straight water took more than twice as many bad turns as normal mice did.
But the demented mice fed caffeine found the platforms about as well as the normal mice.
Furthermore, their brains contained fewer plaques and lower beta-amyloid levels than the brains of mice that drank straight water.
"There were rather striking benefits'' of caffeine, said Dr. Gary Arendash of USF's Florida Alzheimer's Disease Research Center and lead author on the journal article. "There was reversal of memory impairment in mice, which leads us to believe that caffeine could be a very attractive treatment for the disease.''
Caffeine did not improve the performance of normal mice, ruling out the possibility that extra adrenaline led to better scores.
A complex disease
William Thies, chief medical officer for the Alzheimer's Association, called the study interesting but noted that other substances have reduced beta-amyloid and improved cognition in mice, but have flopped in humans.
Human Alzheimer's is a complex constellation of symptoms and events that destroy brain cells. Scientists are far from understanding how these factors interrelate.
Arendash acknowledges the limitations of mouse studies and wants to move quickly into human clinical trials on caffeine. He notes that a recent Finnish epidemiological study indicated that people with Alzheimer's drank less coffee over the course of their lives than people of similar ages who did not have Alzheimer's.
People with Parkinson's disease and Type II diabetes also reported less coffee consumption than healthy people of similar ages.
Such backward-looking surveys have limited use. People often underestimate or exaggerate their lifestyle choices. And maybe coffee drinkers exercised more, ate their veggies or had other habits that explain any health differences later in life.
"We are not saying this is the silver bullet,'' Arendash said. "But there is something about this compound that has benefits for aging bodies.''
The true test would be human clinical trials, but caffeine would face several hurdles.
Even a small, pilot trial can cost hundreds of thousands of dollars, Arendash said.
Caffeine can't be patented, so the drug manufacturers that bankroll most Alzheimer's trials are unlikely to show interest.
Caffeine would have one advantage when it comes to human trials, Thies said.
"It has a very long safety history and is broadly distributed in the population,'' he said. "You have a much less chance of hurting anybody.''
Stephen Nohlgren can be reached at (727) 893-8442 or firstname.lastname@example.org.