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Neurosurgery:
doi: 10.1227/01.neu.0000450230.17042.b2
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Morning Joe or After-Dinner Espresso? Improved Memory Consolidation After Caffeine Administration

Kelly, Kathleen M. BA; Mikell, Charles B. MD; McKhann, Guy M. II MD

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Columbia University Medical Center New York, New York

Caffeine has long been touted as a cognitive enhancer, promoting vigilance, improving reaction times, and facilitating passive learning.1 However, caffeine's effect on memory is contentious at best, with inconsistent effects on short-term memory and few evaluations of long-term memory.1 Since the majority of studies have used paradigms to evaluate short-term memory, caffeine has often been administered before a task in order to observe its effect on memory retrieval. Yet retrieval is only 1 element of the memory process. In recent work published in Nature Neuroscience, Borota and colleagues further evaluated caffeine's effects on memory.2 They posited that caffeine may improve long-term memory consolidation, and may therefore be more effective if taken after, rather than before, task training.

To test this hypothesis, the team conducted a randomized, double-blind, placebo-controlled trial at Johns Hopkins exploring memory consolidation in caffeine-naïve, healthy, young volunteers (average age = 21). On day 1, participants performed an incidental encoding task involving visual images in an indoor-outdoor judgment paradigm. After the task, participants received either placebo or 200 mg of caffeine, a dose roughly equivalent to 1 short, 8-ounce cup of Pike Place Starbucks coffee.3 Baseline, 1-hour, and 3-hour saliva samples were obtained to measure caffeine metabolite levels. On day 2, the participants returned to perform a second task to evaluate their recognition performance. Images included identical items from the previous task (targets), new items (foils), and similar items (lures). Identification of lures in tasks such as this one has been previously associated with hippocampal activity.4 Participants who had received caffeine were significantly more likely to report a lure as “similar” rather than “old” when compared to the placebo group (P = .04). However, there was no difference between groups in correctly identifying targets (P = .27) or rejecting foils (P = .44) (Figure). These findings imply that caffeine consolidated memory in the experimental group such that their ability to discriminate images at 24 hours was improved.

Figure. Caffeine adm...
Figure. Caffeine adm...
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In order to rule out the effect of caffeine on retrieval, the group modified the experiment to administer the same dose of caffeine 1 hour prior to the discrimination task on day 2. There was no significant difference between the caffeine and placebo groups, suggesting that caffeine does not have a direct effect on retrieval. Finally, to assess dosing, the team repeated the experiment using 100 mg, 200 mg, and 300 mg doses of caffeine. Ultimately, the 100 mg group did not significantly differ from placebo; and was significantly lower than the 200 mg group (P = .03). The 300 mg group trended higher compared to placebo but was not significant (P = .07), likely due to insufficient power. However, when the 200 mg and 300 mg groups were combined and compared to the 100 mg and placebo groups, significance was achieved (P = .007), suggesting that 200 mg may be the minimum dose required to observe effect.

The present study demonstrates that a 1-time dose of caffeine administered after an incidental learning task enhances a participant's ability to differentiate similar images in a task 24 hours later. These results suggest that caffeine intake improves long-term memory consolidation. These results are compelling for both the neurosurgical patient and neurosurgeon alike. Caffeine has previously been shown to be neuroprotective in animal models of neurodegenerative disease, including Parkinson disease,5 Alzheimer disease,6 and even age-related memory loss.7 These new findings, taken together with previous work studying caffeine and memory, demonstrate that caffeine likely has benefits beyond prevention of neuronal loss. Given that older adults have been shown to be more susceptible to performance-improving effects of caffeine,8 it is possible that the elderly population may also gain greater memory improvement than younger adults. Future studies are needed to articulate the mechanisms of caffeine's effects on long-term memory, the temporal relationship between caffeine intake and memory processing, and the age dependence of caffeine's potential benefits.

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REFERENCES

1. Nehlig A. Is caffeine a cognitive enhancer? J Alzheimers Dis. 2010;20(suppl 1):S85–S94.

2. Borota D, Murray E, Keceli G, et al.. Post-study caffeine administration enhances memory consolidation in humans. Nat Neurosci. 2014;17(2):201–203.

3. Pike Place® Roast. Starbucks 2014. Available at: http://www.starbucks.com/menu/drinks/brewed-coffee/pike-place-roast-size=2. Accessed March 21, 2014.

4. Yassa MA, Stark CE. Pattern separation in the hippocampus. Trends Neurosci. 2011;34(10):515–525.

5. Chen JF, Xu K, Petzer JP, et al.. Neuroprotection by caffeine and A(2A) adenosine receptor inactivation in a model of Parkinson's disease. J Neurosci. 2001;21(10):RC143.

6. Arendash GW, Schleif W, Rezai-Zadeh K, et al.. Caffeine protects Alzheimer's mice against cognitive impairment and reduces brain beta-amyloid production. Neuroscience. 2006;142(4):941–952.

7. Sallaberry C, Nunes F, Costa MS, et al.. Chronic caffeine prevents changes in inhibitory avoidance memory and hippocampal BDNF immunocontent in middle-aged rats. Neuropharmacology. 2013;64:153–159.

8. Jarvis MJ. Does caffeine intake enhance absolute levels of cognitive performance? Psychopharmacology (Berl). 1993;110(1-2):45–52.

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