Coffee and Alzheimer’s Disease

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Alzheimer’s Disease (AD) is the most frequent cause of dementia. It is estimated that between 50-70% of people with dementia suffer from AD24. In addition, approximately one person out of twenty over the age of 65 suffers from AD, as opposed to less than one person in a thousand under the age of 6525. Approximately 26 million people suffer from AD.  By 2025, the percentage of people in the EU aged over 65 is predicted to rise from 15.4% of the population to 22.4%, which is likely to correlate with a rise in AD26.

In 2014 Alzheimer Europe published an updated systematic review of papers reporting the prevalence of dementia.  The authors concluded that that for the majority of age groups dementia prevalence has not changed significantly over the last few decades.  However, they did report a higher prevalence in older females than was previously thought27.

AD, a neurodegenerative disease, leads to progressive cognitive decline and the accumulation of β-amyloïd peptide (Aβ) in the brain. Some forms of AD are due to the mutation of genes coding for the precursor of Aβ, presenilin 1 and 2. Genetic factors interact with surrounding environmental factors and the influence of these additional factors, deleterious or protective, remains largely unknown.

Coffee, caffeine and risk of Alzheimer’s disease

The majority of human epidemiological studies suggest that regular coffee/caffeine consumption over a lifetime reduces the risk of developing AD, particularly in the elderly. Coffee/caffeine appears to be particularly beneficial before the occurrence of the disease i.e. during the pre-morbid phase.

A 2012 case control study considered the evidence from human and animal models suggesting a role for caffeine in protecting against AD.  The results suggested that coffee/caffeine intake is associated with reduced risk, or delayed onset of dementia particularly in those with mild cognitive impairment28.

In the first meta-analysis concerning the effects of coffee/caffeine on AD, four studies were identified (two case-control and two cohort studies) as carried out between 1990 and 200229-32. There was a clear protective effect of coffee consumption. However, there was a large heterogeneity across the studies33.

A further meta-analysis of the relation between coffee/caffeine intake and the risk of AD, suggested that the summary risk ratio reached 0.80-0.83 for Alzheimer’s disease after adjustment for smoking and hypertension14.

Among the most prominent studies, a case-control study, including 54 patients and 54 controls matched for age and sex, showed that caffeine intake (199mg in controls vs 74mg in cases) was inversely associated with AD (risk ratio 0.40), independently of other confounding variables29.

Another study on the risk factors of AD, followed up with 4,615 subjects over five years (194 AD cases, 3,894 cognitively ‘normal’ controls, and 527 exclusions). It found that the use of non-steroidal anti-inflammatory drugs, wine consumption, coffee consumption, and regular physical activity were associated with a reduced risk of AD (risk ratio of 0.69 for coffee). Interestingly, there was no protection for tea consumers in this study30.

Low coffee intake was also reported to be related to mental disability after a 25-year follow-up of 716 Finnish men34.

In another study, 1,409 individuals aged 65 to 79 were examined after 21 years’ follow-up. Coffee consumption in midlife decreased the risk of AD and dementia in the elderly, with the lowest risk (65% decrease) found in people who drank 3–5 cups/day35.

A further Finnish study measured cognitive status after a median follow-up of 28 years, and coffee consumption was not related to cognitive performance or dementia in old age36.

Finally in the Honolulu-Asia Aging Study, there was no link found between coffee consumption and midlife dementia or cognitive impairment (the age of the subjects was between 51 and 53 years old)37.

Mechanism of action for caffeine

A number of animal studies point to possible mechanisms of action behind coffee/caffeine’s effects on AD risk.

In one study, caffeine in drinking water, given to transgenic mice that develop AD-like symptoms around 8 months of age, improved learning and memory and reduced the concentration of Aβ peptide and presenilin in the hippocampus, the main brain structure involved in memory38.

Moreover, these effects were also found when caffeine treatment was started late i.e. once the mice had already developed cognitive deficits. Caffeine seemed to act by reducing the mediators of inflammation39,40.

Caffeinated coffee increased plasma levels of granulocyte-colony stimulating factor (GCSF), which seemed to improve the cognitive performance of AD transgenic mice with the recruitment of bone marrow cells, enhanced synaptogenesis, and increased neurogenesis. Neither a caffeine solution alone nor decaffeinated coffee provided this effect. The authors hypothesize that caffeine might interact with another component in coffee to selectively elevate GCSF41.

Caffeine may also be active at a different level. In an animal study, the long-term consumption of caffeine in drinking water by rats increased cerebrospinal fluid (CSF) production and cerebral blood flow, which directly affects the production of CSF37. Defective CSF production and turnover, with diminished clearance of Aβ, may be one mechanism implicated in the pathogenesis of AD38. This may partly explain the caffeine-induced reduction of brain levels of Aβ peptide although it is not yet known whether this effect also occurs in humans42, 43.

A role for other coffee constituents

Other coffee constituents, which may be involved in coffee’s beneficial effect on AD risk, besides caffeine, have also been studied.

Several animal studies suggest that trigonelline may have neuro-protective properties and improve memory retention44-46.

The polyphenol antioxidant ferulic acid found in coffee, given to mice in drinking water, has been found to protect against cognitive deficits, mainly spatial and working memory, suppress inflammation and prevent the loss of acetylcholine from the cerebral cortex – all factors that characterize the disease47.

There is an increasing number of experimental and human scientific studies suggesting a potentially protective role for caffeine – and potentially also for other coffee compounds e.g. anti-oxidants or anti-inflammatory agents – in the development of AD. However, further studies aimed at identifying the different coffee compounds that appear to be active against the disease, and the mechanism of action, are needed before any firm conclusions can be drawn.

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