Could caffeine worsen symptoms associated with Alzheimer’s disease?

Written by Sharon Salt

Researchers from Universitat Autònoma de Barcelona (UAB; Spain) and Karolinska Institutet (Solna, Sweden) have revealed that long-term consumption of caffeine could lead to negative effects for Alzheimer’s disease (AD), potentially worsening the neuropsychiatric symptoms appearing in those affected by the disorder.
Although memory problems are hallmarks of AD, this dementia is also characterized by neuropsychiatric symptoms called Behavioral and Psychological Symptoms of Dementia (BPSD).

Coffee or caffeine has recently been suggested as prophylaxis for dementia, both in patients with AD and in the normal ageing processes due to its action in blocking adenosine receptors – which may cause dysfunctions and diseases in old age. However, recent claims have suggested that once the cognitive but also the NPS symptoms are developed, caffeine may actually exert the opposite effects.

In the study, which was published in Frontiers in Pharmacology, scientists studied the long-term effects of a low dose of caffeine in 3xTg-AD mice compared with age-matched non-transgenic counterparts with normal ageing. The animals were treated (water or caffeine in drinking water) from adulthood (6 months of age) until middle-aged (13 months of age), which in 3xTg-AD mice correspond to onset of cognitive impairment and advanced stages, respectively.

“The mice develop AD in a very close manner to the human patients with early onset form of the disease. They not only exhibit the typical cognitive problems but also a number of BPSD-like symptoms, so it is a valuable model to address whether the benefits of caffeine will be able to compensate its putative negative effects,” explained Raquel Baeta-Corral (UAB), the first author of the study.

Björn Johansson (Karolinska Institutet), a co-author of the study, commented: “We had previously demonstrated the importance of the adenosine A1 receptor as the cause of some of caffeine’s adverse effects. Now, we simulated a long oral treatment with very low doses of caffeine (0.3 mg/ml) equivalent to three cups for a human coffee drinker to answer a question which is relevant for patients with Alzheimer’s, but also for the ageing population in general, and that in humans would take years to be solved since we should wait until the patients were aged.”

The results of the study revealed that caffeine altered the behavior of healthy mice and worsened the neuropsychiatric symptoms of mice with AD. In addition to this, the researchers discovered effects in the majority of variables studies, especially in relation to neophobia.

According to the researchers, in mice with AD, the increase in neophobia and anxiety-related behaviors exacerbates their BPSD-like profile. Learning and memory, which are strongly influenced by anxiety, got little benefit from caffeine.

“Our observations of adverse caffeine effects in an AD model together with previous clinical observations suggest that an exacerbation of BPSD-like symptoms may partly interfere with the beneficial cognitive effects of caffeine. These results are relevant when coffee-derived new potential treatments for dementia are to be devised and tested,” concluded Lydia Giménez-Llort (UAB), the corresponding author.

Sources: Baeta-Corral R, Johansson B, Giménez-Llort L. Long-term treatment with low-dose caffeine worsens BPSD-like profile in 3xTg-AD mice model of Alzheimer’s disease and affects mice with normal aging. Front. Pharmacol. (2018);