Can Caffeine Enhance Short And Long-Term Memory?

Author: federica invrea valentina vurchio
Date: 10/10/2014



Caffeine is a bitter, white crystalline, xanthine, alkaloid and a stimulant drug.
Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants.
In humans, caffeine acts as a central nervous system stimulant, temporarily warding off drowsiness and restoring alertness.
It is the world's most widely consumed psychoactive drug. Beverages containing caffeine are coffee, tea, soft drinks and energy drinks.

IUPAC name : 1,3,7-Trimethylpurine-2,6-dione
Formula : C 8 H 10 N 4 O 2
Molecular Mass : 194.19 g/mol
Density : 1.23 g/cm 3

Caffeine is classified by the Food and Drug Administration as generally recognized as safe because toxic doses (over 10 grams for an average adult) are much higher than typically used doses (fewer than 500 milligrams).
Ordinary consumption has low health risks, even when carried on for years. There may be a modest protective effect against some diseases, including Parkinson's disease, heart disease, and certain types of cancer. Some studies have however found modest protective effect against Alzheimer disease, but the evidence is inconclusive.
Some people experience sleep disruption if they consume caffeine, especially during the evening hours, but others show little disturbance and the effect of caffeine on sleep is highly variable.
Recent studies, for the first time, correlated the assumption of caffeine to the enhance of memory consolidation. It were considered both the effects on short-term memory (working memory) and long-term memory.


Working memory

Working memory is the system that actively holds multiple pieces of transitory information in the mind, where they can be manipulated. It is generally used synonymously with short-term memory.
Working memory includes subsystems that store and manipulate visual images or verbal information, as well as a central executive that coordinates the subsystems. It includes visual representation of the possible moves, and awareness of the flow of information into and out of memory, all stored for a limited amount of time.
Working memory tasks require monitoring (manipulation of information or behaviors) as part of completing goal-directed actions.
Parts of the brain involved in working memory are the frontal cortex, parietal cortex, anterior cingulate and parts of the basal ganglia.
Working memory is dependent upon dopaminergic modulation of pre-frontal cortex function and contributes strongly to performance on cognitive ability tests.

Study: Caffeine enhances working memory for extraverts

Luke D. Smillie and Elif Gökçen, using a randomized double-blind placebo-controlled design, examined the effects of caffeine on working memory (WM) as a function of extraverted personality (Caffeine enhances working memory for extraverts, 2010).
Based on previous researches, they attributed psychobiological effects of caffeine to indirect potentiation of dopamine (DA) activity.
Specifically, caffeine may facilitate DA release through blockade of adenosine, a nucleoside that inhibits release of catecholamines and other neurotransmitters. Caffeine blocks adenosine release at A1 and A2a receptor sites, the latter of which are concentrated in DA rich brain regions, including the nucleus accumbens and striatum.
In addition to this, the view that caffeine may potentiate DA activity through antagonistic action at A2a–D2 receptor sites is consistent with similarities between the effects of caffeine and that of selective DA agonists.
It was found that individual differences in response to caffeine correspond with DA-related person characteristics.
One such variable is extraversion, a personality dimension reflecting sociable, bold and outgoing behaviour. Extraversion is highly heritable, and several biologically-inspired theories link this phenotype with variation in DA functioning.
In support of this, studies have linked extraverted personality with hormone response to DA agonists and antagonists and genetic markers of DA.
They investigated the interactive effect of caffeine and extraversion on WM, assessed using the widely-known N-Back task.
For this study, sixty healthy adults were recruited; all participants attended two separate sessions (5–12 days apart) and were instructed to abstain from caffeinated consumables (coffee, chocolate) on both days of testing.
In one session participants were administered caffeine (200 mg caffeine tablet), while in the other they received a placebo (100 mg vitamin supplement tablet). Drug order was counterbalanced and blind to both subject and experimenter, and tablets were closely matched for size, shape and colour.
Extraversion was assessed prior to drug/placebo administration in the first session using the Revised Eysenck Personality Questionnaire.
To allow sufficient time for caffeine to enter the bloodstream, there was a 25-min delay between drug administration and the commencement of the experiment: after this period the experimenter started the N-Back.
This study reveals that caffeine facilitates WM performance for extraverts but not for introverts.
LD Smillie et al. suggest that their findings are highly interpretable in terms of DA function, a common neurochemical denominator linking caffeine, WM and extraversion.
Working memory is not part of long term-memory, but is important for long-term memory to function. Working memory holds and manipulates information for a short period of time, before it is either forgotten or encoded into long-term memory.
Then, in order to remember something from long-term memory, it must be brought back into working memory. If working memory is overloaded it can affect the encoding of long-term memory.


It is currently not known whether caffeine has an enhancing effect on long-term memory in humans.
Hippocampus belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation.
In addition to the hippocampus, several other regions may have a role in consolidating memories, including the anterior cingulate cortex and the medial pre-frontal cortex.
Other brain regions may have a role in modulating consolidation such as the basolateral amygdala and mesolimbic dopaminergic areas.

Study: Post-study caffeine administration enhances memory consolidation in humans

In a recent study published on Nature Neuroscience, D. Borota et al. used post-study caffeine administration to test its effect on memory consolidation using a behavioral discrimination task (Post-study caffeine administration enhances memory consolidation in humans, 2014).
Caffeine effects on long-term memory have not been investigated in detail. The general consensus among past studies is that caffeine has little or no effect on long-term retention.
However, caffeine has been always administered before learning; thus, effects on memory are impossible to dissociate from other effects of caffeine such as increased arousal, vigilance, attention and processing speed.
In this study, the authors used a post-study design (drug administered after subjects have had an opportunity to study the material) based on animal studies, where effects of certain agents on memory consolidation are optimally detected after the learning experience.
They conducted a randomized, double-blind, placebo-controlled trial in 160 healthy, caffeine-naive participants (ages between 18 and 30).
This is the outline of study design (Fig. a).

Day 1 (0 hour): Participants studied images of objects, then received either 200 mg of caffeine or placebo. They collected salivary samples at baseline.
Day 1 (1 hour): Collection of salivary samples.
Day 1 (3 hours): Collection of salivary samples.
Day 2 (24 hours): They collected salivary samples. Then they evaluated participants' recognitions performance using different items:
TARGETS = items they saw the previous day
FOILS = new items
LURES = items that were similar but not identical to ones they saw before. Correctly identifying these lures as “similar” has been previously shown to be associated with hippocampal activity.
Participants who received caffeine were more likely to call lure items “similar” rather than “old” compared to participants who received the placebo (Fig. b), whereas were found no group differences in rates of target hits (Fig. c) or foil rejection (Fig. d).

This suggests that basic recognition memory (recognition of targets and foils) was unalterated. On the other side, the correct identification of lures indicates that consolidation of long-term memory, mediated by hippocampal activity, was enhanced by consuming caffeine.
In a second time, they repeated the experiment with a placebo and different doses of caffeine (100 mg, 200 mg, 300 mg) to determine whether there was an optimal dose range.
Performance for the 100 mg caffeine condition was not significantly different from that for placebo.
Performance for the 300 mg caffeine condition was marginally higher than that for placebo, but not different from the 200 mg caffeine condition.
Thus, they concluded that a dose of at least 200 mg was required to observe the enhancing effect of caffeine on consolidation of memory.
Numerous studies in animals have shown that caffeine has neuroprotective effects.
A recent study suggests that caffeine in floral nectar may boost memory for reward in honeybees, suggesting that the mnemonic effects of caffeine may not be limited to mammals.
No study to actual knowledge has demonstrated a positive effect of caffeine on human long-term memory while excluding non-mnemonic effects.
These results demonstrate that caffeine enhanced consolidation once these effects are appropriately controlled.
Limitations of this study include subjects’ awareness of being involved in a caffeine study and the final sample size for the 300 mg dose was small (10 subjects).
Although the mechanisms by which caffeine enhances memory consolidation remain largely unclear, there are several possibilities:
1. By blocking adenosine, caffeine can prevent it from inhibiting norepinephrine, which has positive effects on consolidation of memory. They have previously demonstrated a relationship between norepinephrine and pattern separation.
2. Caffeine acts in the CA2 region of the hippocampus, which is highly enriched in adenosine A1 receptors, enhancing long-term potentiation in this subfield, which may have a role in certain types of memories.


Recent researches demostrated that caffeine enhanced short and long-term memory consolidation, although the mechanisms are still largely unclear.
Given the widespread use of caffeine and the growing interest in its effects, the understanding of the mechanisms by which caffeine can potentiate memory is a question of critical importance.

Author: Federica Invrea e Valentina Vurchio
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