Caffeine appears to have a positive effect on so-called “tau deposits” in Alzheimer’s disease, scientists have found. Tau deposits are proteins that, together with beta-amyloid plaques, are some of the characteristic features of Alzheimer’s disease.
These deposits interfere with the communication of nerve cells in the brain, and can cause nerve degeneration. No drug is currently available to prevent this process. So researchers led by Dr. Christa Muller from the University of Bonn, Germany, took a look at caffeine.
It is an “adenosine receptor antagonist,” meaning it blocks receptors in the brain that are activated by adenosine. Blocking the adenosine receptor subtype A2A may play a particularly important role.
The team created a compound with caffeine-like effects, a water-soluble A2A antagonist called MSX-3. It specifically blocks only A2A adenosine receptors. In doing so, it is significantly more effective than caffeine while having fewer side effects.
The compound was tested on mice which were altered to have a tau protein that would lead to the early development of Alzheimer’s symptoms. The Alzheimer’s-prone mice were given this A2A antagonist for several weeks, and achieved significantly better results on memory tests — particularly spatial memory — than those given placebo. Full results are published in the journal Neurobiology of Aging.
The team writes, “Epidemiologic evidences support that habitual caffeine intake prevents memory decline during aging and reduces the risk of developing Alzheimer’s disease.”
Commenting on their study, they explain, “We found that chronic caffeine intake [from MSX-3] prevents from the development of spatial memory deficits in tau mice. Moreover, caffeine treatment mitigated several proinflammatory and oxidative stress markers. Together, our data support that moderate caffeine intake is beneficial in a model of Alzheimer’s disease-like tau pathology, paving the way for future clinical evaluation in Alzheimer’s disease patients.”
Dr. Muller said, “We have taken a good step forward. 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.
She added, “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.”
One of the major studies of “real life” caffeine intake and cognition was carried out in 2012 by Chuanhai Cao, Ph.D., of the University of South Florida. Cao and colleagues monitored blood caffeine levels of 124 people aged 65 to 88 years for two to four years. All had mild cognitive impairment, which can progress to Alzheimer’s disease.
Those with higher blood caffeine levels scored better on tests of memory and thinking processes. No other lifestyle differences were seen.
Cao says, “These intriguing results suggest that older adults with mild memory impairment who drink moderate levels of coffee — about three cups a day — will not convert to Alzheimer’s disease, or at least will experience a substantial delay before converting to Alzheimer’s.”
“The results are consistent with earlier studies on mice,” he adds. Caffeinated coffee was the main source of caffeine in the study.
“We are not saying that moderate coffee consumption will completely protect people from Alzheimer’s disease,” added Cao. “However, we firmly believe that moderate coffee consumption can appreciably reduce your risk of Alzheimer’s or delay its onset.”
A very recent review of the modifiable factors linked to cognition and dementia found that 39 percent of studies on caffeine had positive results. “Acting as a stimulant of the central nervous system, caffeine causes heightened alertness and arousal,” the authors write.
“Caffeine is one type of compound known as methylxanthines whose effects are mainly to block adenosine receptors in the brain, resulting in cholinergic stimulation. It was hypothesized that such stimulation would lead to improved memory.”
Although many small studies appear to demonstrate a protective effect, “given the paucity of large cohort studies, more research is needed to establish causality,” they conclude.
In summary, caffeine has not been proven conclusively to protect against Alzheimer’s disease, but decades of research suggest that it may be effective. While caffeine is known to enhance short-term memory and cognition, there is some evidence that long-term use may protect against cognitive decline or dementia.
With the large economic and emotional impact of Alzheimer’s disease, it is vital that we identify potential triggers. Moderate consumption of caffeinated coffee is generally safe for healthy people, so would provide a simple protective strategy, if its benefit is confirmed in more reliable studies.
Laurent, C. et al. Beneficial effects of caffeine in a transgenic model of Alzheimer’s disease-like Tau pathology. Neurobiology of Aging, 31 March 2014 doi:10.1016/j.neurobiolaging.2014.03.027
Cao, C. et al. High blood caffeine levels in MCI linked to lack of progression to dementia. Journal of Alzheimers Disease. 19 March 2012 doi: 10.3233/JAD-2012-111781
Beydoun, M. A. et al. Epidemiologic studies of modifiable factors associated with cognition and dementia: systematic review and meta-analysis. BMC Public Health. 24 June 2014 doi: 10.1186/1471-2458-14-643