Neuroscience behind that perfect cup of morning coffee

Yi-Ting Wang (Tina) is a prospective neuroscientist at the starting point of her scientific career. She uses her little grey cellstrying to solve some of the 21st centurys most fascinating problems in Imperial College London. Like the entomologist in search of colourful butterflies, my attention has chased in the gardens of the grey matter cells with delicate and elegant shapes, the mysterious butterflies of the soul, whose beating of wings may one day reveal to us the secrets of the mind.’  -Santiago Ramon y Cajal

If you are an avid coffee drinker like me, the best way to kick a day off is brewing that one tasty cup of sweet-smelling morning coffee, or grab one at your favourite coffee shop on the way to the workplace. During the day, you probably need some more cups of coffee to keep you going. The active ingredient in coffee is caffeine, the most widely used psychoactive drug in the world. How does the whole process actually work, and how does caffeine affect our brain? Lets reveal the secret of this magical brain fuel from a neuroscientific perspective.

How does caffeine act on our brain?

It’s normal to grow tired as the day progresses because our brains naturally secrete a molecule called adenosine. Briefly, adenosine influences attention, alertness, and sleep. Adenosine builds up in our brain and when it reaches a certain level, our body knows its bedtime. In simple words, caffeine hijacks this system by competing with adenosine for the receptors. By blocking the action of adenosine, we end up feeling more alert and awake (Ribeiro and Sebastião, 2010). It is worth noticing that considerable amount of research reported that coffee can improve cognitive performance and decrease the risk for neurodegenerative disease such as Parkinsons disease (PD) and Alzheimers disease (AD).

Coffee every day, keep doctors away?

Three different epidemiological studies performed in Spain (Jimenez-Jimenez et al., 1992), Germany (Hellenbrand et al., 1996) and Sweden (Fall et al., 1999) reported an inverse, dose-responsive relationship between coffee consumption and the risk of developing PD. Two meta-analyses also showed that the risk of developing PD decreased by 31% (Hernan et al., 2002) and 25% (Costa et al., 2010) respectively in coffee drinkers compared to non-coffee drinkers. However, a more recent case control study suggested only a weak inverse association between coffee intake and the risk of PD (van der Mark et al., 2014). Though the debate is still going on, experimental studies have identified a possible mechanism behind caffeines potential preventative role in the development of PD.

Classically the primary pathology of PD involves the degeneration of dopaminergic neurons that originate in the substantia nigra and project to the striatum. Striatum is a principal component of the basal ganglia. Common PD symptoms such as slow movement, tremors, and rigidity are resulted from the cell death in basal ganglia and their connecting pathways. Low dose of caffeine was shown to mainly antagonise adenosine A2A receptors. The blockade of A2A receptors stimulates dopaminergic D2 receptors and as a result increases motor activity and improves motor deficits in PD models (Fenu and Morelli, 1998), (Kuwana et al., 1999).

A wealth of studies suggested that regular and moderate coffee intake over a lifetime reduces the risk of developing AD. A study published in 2012 gathered preclinical and clinical evidence and found a protective role of caffeine against AD. Results showed that caffeine can reduce risk, or delay onset of dementia. The effect was particularly evident in mild cognitive impairment patients (Cao et al., 2012). Among the most prominent studies, a case-control study showed that caffeine consumption was inversely associated with AD development (Maia and de Mendonça, 2002). In CAIDE study, 1409 elderly were analysed after a 21 yearsfollow-up. Coffee consumption in midlife was shown to decrease the risk of AD and dementia, with the lowest risk (65% decrease) found in people who drank 35 cups/day (Eskelinen et al., 2009). Animal studies helped us identify the possible mechanisms behind coffees effects on AD risk. Dr. Gary Arendash and colleagues found that caffeine improved learning and memory ability of transgenic mice and reduced the concentration of β-amyloid and presenilin in the hippocampus, the main brain structure involved in memory (Arendash et al., 2006). Caffeine also showed to reduce inflammatory mediators, which is another possible explanation of why it could ameliorate AD progression (Arendash et al., 2009; Cao et al., 2009).

How much coffee can we drink?

We have discussed some effects of caffeine on the brain based on different research findings. However, so far most of the evidence for both benefits and adverse effects of caffeine were derived mainly from observational studies, which means we couldnt draw any conclusion of caffeines causal effect on brain function. This awaits further randomised-controlled studies to confirm. Over the last decade, health authorities around the world have concluded that coffee/caffeine consumption is not harmful at levels of 300-500 mg daily (around 3-5 cups of coffee) (Nehlig, 2016). Back to the question, how much can we drink? Just remember moderation is the key, and be a happy coffee drinker!

 

References

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 (2009) Caffeine reverses cognitive impairment and decreases brain amyloid-β levels in aged Alzheimers disease mice. Journal of Alzheimers Disease 17(3):661-80.

Arendash GW, Schleif W, Rezai-Zadeh K, Jackson EK, Zacharia LC, Cracchiolo JR, Shippy D, Tan J (2006) Caffeine protects Alzheimers mice against cognitive impairment and reduces brain β-amyloid production. Neuroscience 142(4):941-52.

Cao C, Cirrito JR, Lin X, Wang L, Verges DK, Dickson A, Mamcarz M, Zhang C, Mori T, Arendash GW, Holtzman DM, Potter H (2009) Caffeine suppresses amyloid-β levels in plasma and brain of Alzheimers disease transgenic mice. Journal of Alzheimers Disease 17(3):681-97.

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 (2012) High blood caffeine levels in MCI linked to lack of progression to dementia. Journal of Alzheimers Disease 30(3):559-72.

Costa J, Lunet N, Santos C, Santos J, Vaz-Carneiro A (2010) Caffeine exposure and the risk of Parkinsons disease: a systematic review and meta-analysis of observational studies. Journal of Alzheimers Disease 20 Suppl 1:S221-38.

Eskelinen MH, Ngandu T, Tuomilehto J, Soininen H, Kivipelto M (2009) Midlife coffee and tea drinking and the risk of late-life dementia: a population-based CAIDE study. Journal of Alzheimers Disease 16(1):85-91.

Fall PA, Fredrikson M, Axelson O, Granérus AK (1999) Nutritional and occupational factors influencing the risk of Parkinsons disease: a case-control study in southeastern Sweden. Movement Disorders 14(1):28-37.

Fenu S. and Morelli M (1998) Motor stimulant effects of caffeine in 6-hydroxydopamine-lesioned rats are dependent on previous stimulation of dopamine receptors: a different role of D1 and D2 receptors. The European Journal of Neuroscience 10(5):1878-84.

Hellenbrand W, Seidler A, Boeing H, Robra BP, Vieregge P, Nischan P, Joerg J, Oertel WH, Schneider E, Ulm G (1996) Diet and Parkinsons disease. I: A possible role for the past intake of specific foods. Results from a self-administered food-frequency questionnaire in a case-control study. Neurology 47(3):636-43.

Hernán MA, Takkouche B, Caamaño-Isorna F, Gestal-Otero JJ (2002) A meta-analysis of coffee drinking, cigarette smoking, and the risk of Parkinsons disease. Annals of Neurology 52(3):276-84.

Jimenez-Jimenez FJ, Mateo D, Giménez-Roldan S (1992) Premorbid smoking, alcohol consumption, and coffee drinking habits in Parkinsons disease: a case-control study. Movement Disorders 7(4):339-44.

Kuwana Y, Shiozaki S, Kanda T, Kurokawa M, Koga K, Ochi M, Ikeda K, Kase H, Jackson MJ, Smith LA, Pearce RK, Jenner PG (1999) Antiparkinsonian activity of adenosine A2A antagonists in experimental models. Advances in Neurology, 80:121-3.

Maia L and de Mendonça A (2002) Does caffeine intake protect from Alzheimers disease? European Journal of Neurology 9(4):377-82.

Nehlig A (2016) Effects of coffee/caffeine on brain health and disease: What should I tell my patients? Practical Neurology 16(2):89-95.

Ribeiro JA and Sebastião AM (2010) Caffeine and adenosine. Journal of Alzheimers Disease 20 Suppl 1:S3-15.

van der Mark M, Nijssen PC, Vlaanderen J, Huss A, Mulleners WM, Sas AM, van Laar T, Kromhout H, Vermeulen R (2014) A Case-Control Study of the Protective Effect of Alcohol, Coffee, and Cigarette Consumption on Parkinson Disease Risk: Time-Since-Cessation Modifies the Effect of Tobacco Smoking. PLoS One 9(4):e95297.

Advanced reading

Fredholm BB, Bättig K, Holmén J, Nehlig A, Zvartau EE (1999) Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacological Reviews 51(1):83-133.

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