Two cups of coffee after learning may cure your forgetful streak

Like most junkies, I struggle to come up with excuses to justify my addiction. Lucky for me, increasing evidence is supporting my semi-hourly coffee habit: caffeine, the world’s favourite drug, not only keeps you awake and alert, but may also boost your memory.

Perhaps in an effort to excuse their own coffee addiction, many research groups have studied whether caffeine enhances memory. The results, unfortunately, are highly mixed. One study, for example, found that 200mg of caffeine – roughly the amount in two cups of drip coffee – consumed before a memory-taxing game enhanced working memory, the ability to flexibly maintain and manipulate information in your head to solve a problem. The catch? Only if you’re an extrovert. In a separate cohort of volunteers, 75mg of caffeine (roughly that in a cup of espresso) taken together with glucose on an empty stomach helped stabilize a new verbal memory. This is called “memory consolidation”, whereby new and unstable memories are moved into semi-permanent storage. However, in that study caffeine by itself had little effect on memory.

One problem with these previous studies is that caffeine was always given prior to learning or testing. This makes interpreting any improvements in performance difficult: is caffeine directly boosting memory or is it enhancing performance indirectly through increasing attention, vigilance and/or processing speed, thus giving the appearance of memory gain?

D Borota et al. Post-study caffeine administration enhances memory consolidation in humans. Nature Neuroscience, published online Jan 12, 2014. doi:10.1038/nn.3623

To get to the bottom of this, researchers from University of California, Irvine* decided to see how caffeine consumed after learning affects memory consolidation. They recruited 160 uncaffeinated adults, a rare breed that drank less than 5 cups of coffee per week and showed no traces of caffeine or its metabolites in their saliva prior to the experiment. In fact, average caffeine intake of most of these “caffeine naïve” people lingered around 70mg a week, coming mostly from chocolate and soda rather than coffee per se. (*The research described in this post was done at Johns Hopkins before the lead author moved to UC Irvine)

The volunteers first looked at a series of images of various objects, such as a saxophone, a sea horse or a basket, and categorized them as either an indoor or outdoor object. Upon completing the task, they immediately popped a pill containing either 200mg of caffeine or a placebo and left the lab.

A day later, the volunteers returned. By now all traces of caffeine and its metabolites had washed out of their system; they were stone-cold sober. The researchers then showed them a new series of pictures, instructing them to identify whether they had previously seen the picture (“old”) or if it was new. To make things harder, researchers sneaked in several pictures extremely similar those shown before. For example, instead of the old picture of a svelte sea horse arching its back, they now presented a “lure” picture of the animal hunched over. This type of “pattern separation” task is considered to reflect memory consolidation to a deeper degree than simple recognition.

Regardless of caffeine intake, both groups had no trouble identifying the old and new pictures. However, as shown below, the caffeinated group outperformed their peers in picking out the lure, with a higher propensity of calling them out as “similar” rather than “old” (though the effect was small and barely reached significance, more on that later). In other words, caffeine seemed to help them retain minute details present in the original pictures. A similar boost in performance was seen when researchers repeated the experiment with 300mg of caffeine (~1 cup more than before), but the advantage disappeared when they dropped the dose down to 100mg. Remember that caffeine was administered after viewing the photos, hence the drug was not increasing attention to detail during the learning process.

White bar is caffeine and grey bar is placebo. Notice the shorter white bar in the "Old" group (fewer lure images identified as old) and taller white bar in the "Similar" group (more images correctly identified as lure).

However, not everyone metabolizes the same 200mg caffeine pill to the same degree. When researchers accounted for individual differences in caffeine absorption and metabolism, they found that participants who broke down the largest amount of caffeine performed worse than those who metabolized slightly less. In other words, there is a sweet spot for caffeine’s memory enhancing powers – go either under or over and you loose that edge.

Finally, what if you waited too long after learning, only to remember to chug that Starbucks mocha the day after? In a separate study, researchers allowed 24hrs for volunteers to consolidate the memory of the initial picture stack before giving them the same caffeine pill, just one hour before the test. This time it didn’t work – these volunteers mixed up similar and old pictures just like the placebo control group. Whatever caffeine is doing, it has to be done during consolidation.

Researchers aren’t quite sure how caffeine induces memory gain, but they have a few ideas. The image discrimination task used here engages the hippocampus, a key brain area involved in learning and memory. It expresses high amounts of the caffeine receptor (adenosine A1 receptor) in its CA2 subregion, thus allowing caffeine to tweak (strengthen?) its function in memory consolidation. Caffeine can also indirectly boost the level of norepinephrine, a neurotransmitter that helps you lay down a memory for good.

While exciting, this study cannot end the debate on whether caffeine improves memory. The effect sizes were small, with some only scraping significance - that is, researchers were only barely able to say with some confidence that the effect is real. This doesn't reflect the quality of the research, but most likely represents individual variance among the volunteers: different gene variants for faster caffeine metabolism, BMI, basal metabolic rate, oral contraceptives and so on. It would also be interesting to see if caffeine boosts memory reconsolidation: when you retrieve a memory, it temporarily becomes labile. Can coffee help the memory restablize?

Unfortunately, we don’t known if caffeine-induced memory gain applies to caffeine junkies like me. But to quote the lead author: one needs to do the experiment with habitual drinkers to find out, but my guess is that it's why we're so awesome!

Many thanks to the principal investigator @mike_yassa for patiently answering my questions over Twitter. You can check out our full conversation in my timeline.

Borota D, Murray E, Keceli G, Chang A, Watabe JM, Ly M, Toscano JP, & Yassa MA (2014). Post-study caffeine administration enhances memory consolidation in humans. Nature neuroscience PMID: 24413697