Caffeine

The effect of caffeine on memory

Effects of caffeine on memory

Caffeine has both good and bad effects, both of which may impact on cognitive performance.

Coffee contains active ingredients other than caffeine which may, directly or indirectly, impact on cognitive performance.

Caffeine appears to be of greater potential significance to older adults.

However, those with hypertension, diabetes, impaired glucose tolerance, or high homocysteine levels, would be wiser to avoid coffee, even if decaffeinated.

Caffeine's main impact is on attention.

It seems clear that caffeine improves alertness and reaction time, but evidence is inconclusive for its effect on higher memory and reasoning processes. It is possible that caffeine may in fact impede memory, where the information is complex or ambiguous.

Caffeine can be helpful in ameliorating the effects of time of day and sleep deprivation on cognitive performance. In normal circumstances (i.e., not prolonged sleep deprivation, or extreme stress), caffeine seems to be more helpful to older adults, in helping them overcome time-of-day effects.

Recent research has demonstrated that caffeine affects blood flow in the brain. It is not yet clear what the implications of this may be.

Caffeine has been implicated in raising blood pressure. High blood pressure is undoubtedly a risk factor for cognitive decline and dementia for those over 60. However, recent studies suggest that, while it is clear that coffee raises blood pressure, it is not clear that caffeine is the culprit.

Brewed coffee raises homocysteine levels. High homocysteine levels in older adults increase the risk of cognitive decline and dementia. Recent research suggests however that caffeine is not the sole ingredient in coffee responsible for the homocysteine-raising effect.

Evidence for the effect of caffeine on glucose regulation is inconclusive as yet, but there is some suggestion that caffeine may be a risk factor for impaired glucose tolerance. Impaired glucose tolerance is a risk factor for cardiovascular disease (and thus, by implication, cognitive decline, since research now indicates that “what is good for the heart is good for the brain”). More direct evidence also suggests that impaired glucose tolerance in older adults is associated with memory problems.

While people clearly build up a tolerance to some of the effects of caffeine, it is not yet clear what the long-term effects of regular caffeine use are. Nor can we say, as yet, what factors are important in determining those long-term effects, although we can speculate that gender, metabolic factors, cardiovascular health, alcohol and tobacco use are all possible influences.

Conclusion: Clearly, caffeine has both good and bad effects, both of which may impact on cognitive performance. Moreover, the main vehicle for caffeine — coffee — contains active ingredients other than caffeine which may, directly or indirectly, impact on cognitive performance. Caffeine does appear to be of greater potential significance to older adults. Overall, the evidence suggests that, while caffeine may help older adults in the later part of the day, those with hypertension, diabetes, impaired glucose tolerance, or high homocysteine levels, would be wiser to avoid coffee, even if decaffeinated. In general, while caffeine may help you overcome factors that lower your cognitive performance, it does not seem that caffeine has any significant direct effect on memory, although it may well help you pay attention.

This is a summary of research into the effects of caffeine on memory. You can download the full report (in pdf format).

Why dark chocolate is good for your heart

A study involving 44 middle-aged overweight men who consumed 70 grams of dark chocolate per day over two periods of four weeks, has found that dark chocolate helps restore flexibility to arteries while also preventing white blood cells from sticking to the walls of blood vessels. Both arterial stiffness and white blood cell adhesion are known factors that play a significant role in atherosclerosis.

http://www.eurekalert.org/pub_releases/2014-02/foas-wdc022714.php

Green tea plus exercise may speed up weight loss

Mice given decaffeinated green tea and regular exercise lost weight and improved their health after 16 weeks. Specifically, they reduced body mass by 27% (on average), reduced abdominal fat by 37%; reduced blood glucose level by 17%, plasma insulin level by 65%, and insulin resistance by 65%..

Neither green tea alone, nor exercise alone, produced such significant changes. The amount of green tea was a lot: the equivalent of 8-10 cups a day. Decaffeination may not be important; it was done to keep the effects of caffeine out of the study.

Caffeine gives honeybees memory boost

honeybee

Caffeine occurs naturally in the nectar of coffee and citrus flowers. A study of honeybees has revealed that those fed on caffeinated nectar were three times more likely to remember a flower's scent than bees fed sugar alone, after 24 hours. After three days, they were still twice as likely to remember the flower than those fed sugar alone.

Caffeine may block inflammation linked to cognitive impairment

A mouse study indicates that caffeine can help prevent inflammation occurring in the brain, by blocking an early response to cell damage.

Caffeine has been associated with a lower of developing Alzheimer's disease in some recent studies. A recent human study suggested that the reason lies in its effect on proteins involved in inflammation. A new mouse study provides more support for this idea.

In the study, two groups of mice, one of which had been given caffeine, were exposed to hypoxia, simulating what happens in the brain during an interruption of breathing or blood flow. When re-oxygenated, caffeine-treated mice recovered their ability to form a new memory 33% faster than the other mice, and the caffeine was observed to have the same anti-inflammatory effect as blocking interleukin-1 (IL-1) signaling.

Inflammation is a key player in cognitive impairment, and IL-1 has been shown to play a critical role in the inflammation associated with many neurodegenerative diseases.

It was found that the hypoxic episode triggered the release of adenosine, the main component of ATP (your neurons’ fuel). Adenosine is released when a cell is damaged, and this leakage into the environment outside the cell begins a cascade that leads to inflammation (the adenosine activates an enzyme, caspase-1, which triggers production of the cytokine IL-1β).

But caffeine blocks adenosine receptors, stopping the cascade before it starts.

The finding gives support to the idea that caffeine may help prevent cognitive decline and impairment.

Coffee helps prevent progression to dementia

A 4-year study of older adults has found that low levels of caffeine were linked to MCI progressing to dementia, apparently by mediating lower levels of anti-inflammatory proteins.

Following on from mouse studies, a human study has investigated whether caffeine can help prevent older adults with mild cognitive impairment from progressing to dementia.

The study involved 124 older adults (65-88) who were thoroughly cognitively assessed, given brain scans, and had a fasting blood sample taken. They were then followed for 2 to 4 years, during which their cognitive status was re-assessed annually. Of the 124 participants, 69 (56%) were initially assessed as cognitively normal (average age 73), 32 (26%) with MCI (average age 76.5), and 23 (19%) with dementia (average age 77). The age differences were significant.

Those with MCI on initial assessment showed significantly lower levels of caffeine in their blood than those cognitively healthy; levels in those with dementia were also lower but not significantly. Those initially healthy who developed MCI over the study period similarly showed lower caffeine levels than those who didn’t develop MCI, but again, due to the wide individual variability (and the relatively small sample size), this wasn’t significant. However, among those with MCI who progressed to dementia (11, i.e. a third of those with MCI), caffeine levels were so much lower that the results were significant.

This finding revealed an apparently critical level of caffeine dividing those who progressed to dementia and those who did not — more specifically, all of those who progressed to dementia were below this level, while around half of those who remained stable were at the level or above. In other words, low caffeine would seem to be necessary but not sufficient.

On the other hand (just to show that this association is not as simple as it appears), those already with dementia had higher caffeine levels than those with MCI who progressed to dementia.

The critical factor may have to do with three specific cytokines — GCSF, IL-10, and IL-6 — which all showed markedly lower levels in those converting from MCI to dementia. Comparison of the three stable-MCI individuals with the highest caffeine levels and the three with the lowest levels, and the three from the MCI-to-dementia group with comparable low levels, revealed that high levels of those cytokines were matched with high caffeine levels, while, in both groups, low caffeine levels were matched to low levels of those cytokines.

These cytokines are associated with inflammation — an established factor in cognitive decline and dementia.

The level of coffee needed to achieve the ‘magic’ caffeine level is estimated at around 3 cups a day. While caffeine can be found in other sources, it is thought that in this study, as in the mouse studies, coffee is the main source. Moreover, mouse research suggests that caffeine is interacting with an as yet unidentified component of coffee to boost levels of these cytokines.

This research has indicated that caffeine has several beneficial effects on the brain, including suppressing levels of enzymes that produce amyloid-beta, as well as these anti-inflammatory effects.

It’s suggested that the reason high levels of caffeine don’t appear to benefit those with dementia is because higher levels of these cytokines have become re-established, but this immune response would appear to come too late to protect the brain. This is consistent with other evidence of the importance of timing.

Do note that in mouse studies, the same benefits were not associated with decaffeinated coffee.

While this study has some limitations, the findings are consistent with previous epidemiologic studies indicating coffee/caffeine helps protect against cognitive impairment and dementia. Additionally, in keeping with the apparent anti-inflammatory action, a long-term study tracking the health and coffee consumption of more than 400,000 older adults recently found that coffee drinkers had reduced risk of dying from heart disease, lung disease, pneumonia, stroke, diabetes, infections, injuries and accidents.

Reference: 

Cao, C., Loewenstein, D. a, Lin, X., Zhang, C., Wang, L., Duara, R., Wu, Y., et al. (2012). High Blood Caffeine Levels in MCI Linked to Lack of Progression to Dementia. Journal of Alzheimer’s disease : JAD, 30(3), 559–72. doi:10.3233/JAD-2012-111781

Freedman, N.D. et al. 2012. Association of Coffee Drinking with Total and Cause-Specific Mortality. N Engl J Med, 366, 1891-1904.

Free downloads

There are a number of documents you can download for free from this website. All of these are in Adobe Acrobat format (pdf).

Most of these are collections of articles from the website:

Active reading

Mnemonics at a glance

Learning another language

Memory in normal aging

Helping your aging memory

Memory impairment in the aging brain

There is also a report on the effects of caffeine on memory and cognition

 

Scent of rosemary may help cognition

Rosemary is a herb long associated with memory. A small study now provides some support for the association, and for the possible benefits of aromatherapy. And a rat study indicates that your attitude to work might change how stimulants affect you.

A small study involving 20 people has found that those who were exposed to 1,8-cineole, one of the main chemical components of rosemary essential oil, performed better on mental arithmetic tasks. Moreover, there was a dose-dependent relationship — higher blood concentrations of the chemical were associated with greater speed and accuracy.

Participants were given two types of test: serial subtraction and rapid visual information processing. These tests took place in a cubicle smelling of rosemary. Participants sat in the cubicle for either 4, 6, 8, or 10 minutes before taking the tests (this was in order to get a range of blood concentrations). Mood was assessed both before and after, and blood was tested at the end of the session.

While blood levels of the chemical correlated with accuracy and speed on both tasks, the effects were significant only for the mental arithmetic task.

Participants didn’t know that the scent was part of the study, and those who asked about it were told it was left over from a previous study.

There was no clear evidence that the chemical improved attention, but there was a significant association with one aspect of mood, with higher levels of the scent correlating with greater contentment. Contentment was the only aspect of mood that showed such a link.

It’s suggested that this chemical compound may affect learning through its inhibiting effect on acetylcholinesterase (an important enzyme in the development of Alzheimer's disease). Most Alzheimer’s drugs are cholinesterase inhibitors.

While this is very interesting (although obviously a larger study needs to confirm the findings), what I would like to see is the effects on more prolonged mental efforts. It’s also a little baffling to find the effect being limited to only one of these tasks, given that both involve attention and working memory. I would also like to see the rosemary-infused cubicle compared to some other pleasant smell.

Interestingly, a very recent study also suggests the importance of individual differences. A rat study compared the effects of amphetamines and caffeine on cognitive effort. First of all, giving the rats the choice of easy or hard visuospatial discriminations revealed that, as with humans, individuals could be divided into those who tended to choose difficult trials (“workers”) and those who preferred easy ones (“slackers”). (Easy trials took less effort, but earned commensurately smaller reward.)

Amphetamine, it was found, made the slackers worked harder, but made the workers take it easier. Caffeine, too, made the workers slack off, but had no effect on slackers.

The extent to which this applies to humans is of course unknown, but the idea that your attitude to cognitive effort might change how stimulants affect you is an intriguing one. And of course this is a more general reminder that factors, whatever they are, have varying effects on individuals. This is why it’s so important to have a large sample size, and why, as an individual, you can’t automatically assume that something will benefit you, whatever the research says.

But in the case of rosemary oil, I can’t see any downside! Try it out; maybe it will help.

Coffee and a healthy diet reduce the risk of Alzheimer’s

Recent studies show why a low-fat, low-carb diet, and caffeinated coffee, help protect against developing Alzheimer’s disease.

Dietary changes affect levels of biomarkers associated with Alzheimer's

In a study involving 20 healthy older adults (mean age 69.3) and 29 older adults who had amnestic mild cognitive impairment (mean age 67.6), half the participants were randomly assigned to a high–saturated fat/high–simple carbohydrate diet (HIGH) and half to a low–saturated fat/low–simple carbohydrate diet (LOW) for four weeks, in order to investigate the effects on biomarkers associated with Alzheimer’s.

For the healthy participants, the LOW diet decreased the level of amyloid-beta 42 in the cerebrospinal fluid, while the HIGH diet increased its level. The HIGH diet also lowered the CSF insulin concentration. For those with aMCI, the LOW diet increased the levels of amyloid-beta 42 and increased the CSF insulin concentration. For both groups, the level of apolipoprotein E in the CSF increased in the LOW diet and decreased in the HIGH diet.

For both groups, the LOW diet improved performance on delayed visual recall tests, but didn’t affect scores on other cognitive measures (bear in mind that the diet was only followed for a month).

The researchers suggest that the different results of the unhealthy diet in participants with aMCI may be due to the diet’s short duration. The fact that diet was bringing about measurable changes in CSF biomarkers so quickly, and that the HIGH diet moved healthy brains in the direction of Alzheimer’s, speaks to the potential of dietary intervention.

Why coffee helps protect against Alzheimer's disease

Support for the value of coffee in decreasing the risk of Alzheimer’s comes from a mouse study, which found that an as yet unidentified ingredient in coffee interacts with caffeine in such a way that blood levels of a growth factor called GCSF (granulocyte colony stimulating factor) increases. GCSF is a substance greatly decreased in patients with Alzheimer's disease and demonstrated to improve memory in Alzheimer's mice.

The finding points to the value of caffeinated coffee, as opposed to decaffeinated coffee or to other sources of caffeine. Moreover, only "drip" coffee was used; the researchers caution that they don’t know whether instant caffeinated coffee would provide the same GCSF response.

There are three ways that GCSF seems to improve memory performance in the Alzheimer's mice: by recruiting stem cells from bone marrow to enter the brain and remove beta-amyloid protein; by increasing the growth of new synapses; by increasing neurogenesis.

The amount of coffee needed to provide this protection, however, is estimated to be about 4 to 5 cups a day. The researchers also believe that this daily coffee intake is best begun at least by middle age (30s – 50s), although starting even in older age does seem to have some protective effect.

Weirdly (I thought), the researchers remarked that "The average American gets most of their daily antioxidants intake through coffee". Perhaps this points more to the defects in their diet than to the wonders of coffee! But the finding is consistent with other research showing an association between moderate consumption of coffee and decreased risk of Parkinson's disease, Type II diabetes and stroke.

A just-completed clinical trial has investigated GCSF treatment to prevent Alzheimer's in patients with mild cognitive impairment, and the results should be known soon.

Reference: 

[2442] Bayer-Carter, J. L., Green P. S., Montine T. J., VanFossen B., Baker L. D., Watson S. G., et al. (2011).  Diet Intervention and Cerebrospinal Fluid Biomarkers in Amnestic Mild Cognitive Impairment. Arch Neurol. 68(6), 743 - 752.

Cao, C., Wang, L., Lin, X., Mamcarz, M., Zhang, C., Bai, G., Nong, J., Sussman, S. & Arendash, G.  2011.Caffeine Synergizes with Another Coffee Component to Increase Plasma GCSF: Linkage to Cognitive Benefits in Alzheimer's Mice. Journal of Alzheimer's Disease, 25(2), 323-335.

Caffeine - news reports

Older news items (pre-2010) brought over from the old website

Caffeine reverses memory impairment in Alzheimer's mice

Consistent with earlier indications that moderate caffeine consumption may protect against memory decline, a study of genetically engineered mice has found that when the old mice began to show memory impairment, those given caffeine for 2 months performed as well as normal aged mice on cognitive tests, while those given plain drinking water continued to do poorly. The Alzheimer's mice received the equivalent of five 8-oz. cups of regular coffee a day (or two cups of Starbucks coffee, or 14 cups of tea). Moreover, the brains of the caffeinated mice showed nearly a 50% reduction in levels of beta amyloid. The effect appears to be through suppression of both β-secretase and presenilin 1 /g-secretase expression. Caffeine had this effect only on those with Alzheimer’s; normal mice given caffeine through adulthood showed no cognitive benefit.

Arendash, G.W. et al. 2009. Caffeine Reverses Cognitive Impairment and Decreases Brain Amyloid-β Levels in Aged Alzheimer's Disease Mice. Journal of Alzheimer's Disease, 17 (3), 661-680.

Cao, C. et al. 2009. Caffeine Suppresses Amyloid-β Levels in Plasma and Brain of Alzheimer's Disease Transgenic Mice. Journal of Alzheimer's Disease, 17 (3), 681-697.

http://www.eurekalert.org/pub_releases/2009-07/uosf-crm070109.php

Midlife coffee drinking reduces risk of dementia

A large, long-running Finnish study has found that those who were coffee drinkers at midlife had lower risk for dementia and Alzheimer’s later in life compared to those drinking no or only little coffee midlife. The lowest risk was found among moderate coffee drinkers (drinking 3-5 cups of coffee/day). Tea drinking was relatively uncommon and was not associated with dementia.

Eskelinen, M.H. et al. 2009. Midlife Coffee and Tea Drinking and the Risk of Late-Life Dementia: A Population-based CAIDE Study. Journal of Alzheimer's Disease, 16(1).

http://www.physorg.com/news151225794.html

Chocolate, wine and tea improve brain performance

A study of over 2000 older Norwegians (aged 70-74) has found that those who consumed chocolate, wine, or tea had significantly better cognitive performance and lower risk of poor cognitive performance than those who did not. Those who consumed all 3 studied items had the best performance and the lowest risks for poor test performance. The associations between intake of these foodstuffs and cognition were dose dependent, with maximum effect at intakes of around 10 grams a day for chocolate and around 75–100 ml a day for wine, but approximately linear for tea. The effect was most pronounced for wine and modestly weaker for chocolate intake. The finding is consistent with research indicating that those who consume lots of flavonoids have a lower incidence of dementia.

[623] Nurk, E., Refsum H., Drevon C. A., Tell G. S., Nygaard H. A., Engedal K., et al. (2009).  Intake of flavonoid-rich wine, tea, and chocolate by elderly men and women is associated with better cognitive test performance. The Journal of Nutrition. 139(1), 120 - 127.

http://www.physorg.com/news149185135.html

Coffee helps you retain mental sharpness later in the day

A recent study of 40 older adults (over 65) confirmed the popular belief in the value of caffeine in helping overcome a decline in mental sharpness later in the afternoon. All the participants (like three-quarters of all people in that age group, studies suggest) described themselves as "morning people". Testing confirmed that they were less alert later in the day. Given coffee, but not told whether it was "real" coffee or decaffeinated, those who drank the regular coffee did not experience mental declines in the afternoon tests. Note that participants were already regular coffee drinkers (and were asked to abstain before arriving for the test).

[1166] Ryan, L., Hatfield C., & Hofstetter M. (2002).  Caffeine reduces time-of-day effects on memory performance in older adults. Psychological Science: A Journal of the American Psychological Society / APS. 13(1), 68 - 71.

http://www.nytimes.com/2002/01/01/health/psychology/01AGIN.html?rd=hcmcp?p=041sRh041sTt436WO012000mo9$ho9mk

Helping memory with "natural" supplements

Do caffeine and glucose help concentration? A recent study found that volunteers who drank a mixture containing caffeine and glucose (as well as trace levels of guarana, ginkgo and ginseng) showed clear improvements in memory and attention. Those who consumed the individual ingredients, or a placebo, did not show such improvements.

Scholey, A. & Kennedy, D. 2003. Report at the British Psychological Society Annual Conference in Bournemouth 13-15 March.

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