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Could drinking espresso coffee reduce the risk of Alzheimer‘s disease?

With a recent study suggesting that components within espresso coffee extract nullified the adverse effects of the Alzheimer‘s-associated tau protein, is drinking coffee a potential lifestyle preventative measure for reducing the risk of such neurodegenerative conditions? Clinical writer Rod Tucker takes a look at the evidence.

There’s no doubt that coffee is a widely consumed beverage and coffee culture has taken the world by storm from the espresso bars of Italy to the commercial giants on seemingly every street corner. Deemed to be one of the most widely traded commodities in the world, around two billion cups of coffee are consumed worldwide each day, according to the British Coffee Association.

Coffee is prepared and drunk in a number of different ways from dehydrated instant varieties revived by adding boiling water, to the perfect European espresso in which high pressure hot water is passed through 5-7g of finely-ground powder to produce an energising 30 ml serving.

For many years, a large proportion of healthcare professionals advised against drinking coffee, particularly for those with anxiety, arrhythmias, palpitations or tachycardia. This was based on the premise that the stimulant effects of caffeine – of which there’s just over 60mg in a single espresso shot – would most likely exacerbate cardiac arrhythmias. However, there is a lack of evidence to support this view. In fact, it seems that the opposite may be true.

For instance, a meta-analysis of seven observational studies including 115,993 individuals concluded that caffeine exposure is not associated with increased risk of atrial fibrillation, and that it may even be protective.

More recently, a 2022 analysis of data from the UK Biobanks, suggested that two to three daily cups of coffee was associated with a lower incidence of cardiac arrhythmias. But coffee is purported to have a plethora of health benefits, which were extolled in a 2017 umbrella review, which concluded that there were large risk reductions for a range of health outcomes when consuming three to four cups of coffee per day.

The risk of Alzheimer‘s disease

One of the intriguing findings identified in the umbrella review was habitual coffee drinking being linked to a 27% lower risk of developing Alzheimer‘s disease. Some of the earliest evidence identifying a possible protective effect against Alzheimer‘s disease, came from a study in 2002.

Using a case-control study, researchers observed a significant and inverse association between caffeine exposure and Alzheimer‘s disease (odds ratio, OR = 0.40, 95% CI 0.25 – 0.67). Moreover, other work appeared to confirm this benefit, with a further study reporting that drinking three to five cups of coffee a day during midlife was associated with a 65% lower risk of developing dementia or Alzheimer‘s disease during later life.

But this observational study evidence can only be used to demonstrate correlation and not causation. That is to say, just because the two factors of coffee and Alzheimer‘s disease are correlated does not mean that one either causes or protects against the other. However, evidence of a plausible biological mechanism, which accounts for this correlation, helps to support the observed relationship.

For instance, it has been found that caffeine prevents the β-amyloid-induced neurotoxicity in cultured cerebellar neurons of rats via blockade of adenosine A2A. In fact, the authors concluded that their study constituted the first in vitro evidence to suggest that blockade of adenosine A2A receptors, may be the molecular target for the observed beneficial effects of consuming caffeine in relation to the development of Alzheimer’s disease.

Despite this biological plausibility, not all observational studies demonstrate a positive relationship between caffeine intake and cognitive disorders. In a 2015 meta-analysis of 19 studies, the authors found that in all 19 studies caffeine intake was not significantly associated with the risk of cognitive disorders including dementia, Alzheimer’s disease, cognitive impairment and cognitive decline (OR = 0.82, 95% CI 0.67 – 1.01).

But if coffee does offer protection against Alzheimer‘s disease, could this arise from components other than caffeine?

Espresso coffee and tau aggregation

With a good deal of research focusing on the possible protective role of coffee, it has also been recognised that coffee is actually a mixture of a number of bioactive compounds. These include polyphenols, especially chlorogenic acids and caffeic acid in roasted coffee beans; alkaloids, such as caffeine and trigonelline; and the diterpenes cafestol and kahweol. So, is it possible that some of these bioactive agents are responsible for the purported protective effect against Alzheimer’s disease?

A recent study set out to address this issue. The researchers used nuclear magnetic resonance to characterise the molecular composition of an espresso coffee extract. Since aggregation of the protein tau is implicated in the pathophysiology of Alzheimer’s disease, the researchers focused on any components that affected this process. In particular, they considered whether any components in the espresso extract could prevent tau aggregation, condensation – which is a purported mechanism initiating aggregation – and the seeding activity of the tau protein whereby further aggregation occurs once tau fibrils have been formed.

The research uncovered several important actions of the espresso coffee extract in relation to tau. First, the extract had an inhibitory effect on tau fibril formation, preventing aggregation and the ability to induce intracellular tau fibrillisation. Second, the extract interfered with early events (condensation), which led to the accumulation of tau. Finally, the tau fibrils that were formed in the presence of the espresso extract not only had a reduced ability to aggregate, but the resulting species displayed either reduced or no cellular toxicity and were unable to ‘seed‘ further aggregation.

Taken together, the findings suggested that the espresso extract was neuro-protective against tau-induced toxicity in cultured cells. In fact, the authors even suggested that ‘based on the bioavailability of coffee components in the brain, and on the results of our study, we expect that moderate coffee consumption may provide a sufficient amount of bioactive molecules to act separately or synergistically as modulators of tau protein aggregation and toxicity‘.

Is it time to start drinking espresso coffee?

The evidence to date indicates that coffee intake may be a protective factor against Alzheimer‘s disease. Moreover, there is data showing neuro-protective effects for many of the bioactive components within coffee. While much of the evidence is derived from observations studies, one Mendelian randomisation study that avoids the influence of confounders, has shown that genetically predicted higher plasma caffeine levels were associated with a non-significant lower risk of Alzheimer’s disease.

With the totality of the evidence appearing to suggest a possible benefit from drinking coffee in relation to the development of Alzheimer‘s disease, the espresso research was cell-based and therefore preliminary in nature.

Nevertheless, whether drinking espresso coffee over a lifetime might reduce the risk of developing Alzheimer‘s disease remains an intriguing thought and certainly provides basis for future studies.