Borota D, Murray E, Keceli G, Chang A, Watabe JM, Ly M, Toscano JP, Yassa MA.
Post-study caffeine administration enhances memory consolidation in humans.
Nat Neurosci. 2014 Jan 12;
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This paper by Borota and colleagues concludes that caffeine administered to people who had been shown various pictures enhanced memory consolidation of those pictures 24 hours later. The authors believe this to be the first study showing caffeine to have “long-term” cognitive benefit in normal humans when administered after a training session. Unfortunately, the data supporting this premise seems weak. First, there were no significant differences between caffeine and placebo groups for the primary endpoints collected using a standard two-tailed analysis—significance was only attained with one-tailed analysis where significance was p<0.10. Even when the authors used a calculated “discrimination index” from these non-significant primary endpoints, the p value was not below 0.05. Second, simply looking at the results from the individual subjects plotted in the graphs, one can see there is near-total overlap between caffeine and placebo groups, which again underscores no practical significance of the data. Thirdly, claims of a dose effect of caffeine on subject memory consolidation are not substantiated, with marginal differences only being present with combinations of various groups or selected comparisons.
In view of the above, it seems unclear how this paper relates to Alzheimer’s disease. Even if truly significant effects had been demonstrated, the study was performed in normal subjects, naïve to caffeine, and presumably without AD-related neuropathology. Thus, the results in this caffeine study cannot relate to our work showing: 1) the long-term effects of caffeine in AD transgenic mice to prevent/reverse cognitive impairment and decrease brain Aβ levels through suppression of both β- and γ-secretases (Arendash et al., 2006; Arendash et al., 2009), or 2) our demonstration that elevated caffeine levels prevent MCI conversion to AD (Cao et al., 2012).
Arendash GW, Schleif W, Rezai-Zadeh K, Jackson EK, Zacharia LC, Cracchiolo JR, Shippy D, Tan J.
Caffeine protects Alzheimer's mice against cognitive impairment and reduces brain beta-amyloid production.
Neuroscience. 2006 Nov 3;142(4):941-52.
Arendash GW, Mori T, Cao C, Mamcarz M, Runfeldt M, Dickson A, Rezai-Zadeh K, Tane J, Citron BA, Lin X, Echeverria V, Potter H.
Caffeine reverses cognitive impairment and decreases brain amyloid-beta levels in aged Alzheimer's disease mice.
J Alzheimers Dis. 2009;17(3):661-80.
Cao C, Loewenstein DA, Lin X, Zhang C, Wang L, Duara R, Wu Y, Giannini A, Bai G, Cai J, Greig M, Schofield E, Ashok R, Small B, Potter H, Arendash GW.
High Blood Caffeine Levels in MCI Linked to Lack of Progression to Dementia.
J Alzheimers Dis. 2012 Jan 1;30(3):559-72.