Long-term caffeine worsens symptoms associated with Alzheimer’s disease
A long-term, low dose of caffeine worsened neophobia (fear of everything new), anxiety-related behaviors, and emotional and cognitive flexibility — while providing only little benefit to learning and memory.
— By Universitat Autonoma De Barcelona
It is well known that memory problems are the hallmarks of Alzheimer’s disease. However, this dementia is also characterized by neuro-psychiatric symptoms, which may be strongly present already in the first stages of the disorder. Known as Behavioural and Psychological Symptoms of Dementia (BPSD), this array of symptoms — including anxiety, apathy, depression, hallucinations, paranoia and sundowning (or late-day confusion) — are manifested in different manners depending on the individual patient, and are considered the strongest source of distress for patients and caregivers.
Coffee and caffeine: good or bad for dementia?
Caffeine has recently been suggested as a strategy to prevent dementia, both in patients with Alzheimer’s disease and in normal ageing processes. This is due to its action in blocking molecules — adenosine receptors — which may cause dysfunctions and diseases in old age. However, there is some evidence that once cognitive and neuro-psychiatric symptoms develop, caffeine may exert opposite effects.
To investigate this further, researchers from Spain and Sweden conducted a study with normal ageing mice and familial Alzheimer’s models. The research, published in Frontiers in Pharmacology, was conducted from the onset of the disease up to more advanced stages, as well as in healthy age-matched mice.
“The mice develop Alzheimer’s disease in a very close manner to human patients with early-onset form of the disease,” explains first author Raquel Baeta-Corral, from Universitat Autònoma de Barcelona, Spain. “They not only exhibit the typical cognitive problems but also a number of BPSD-like symptoms. This makes them a valuable model to address whether the benefits of caffeine will be able to compensate its putative negative effects.”
“We had previously demonstrated the importance of the adenosine A1 receptor as the cause of some of caffeine’s adverse effects,” explains Dr. Björn Johansson, a researcher and physician at the Karolinska University Hospital, Sweden.
“In this study, we simulated a long oral treatment with a very low dose of caffeine (0.3 mg/mL) — equivalent to three cups of coffee a day for a human — to answer a question which is relevant for patients with Alzheimer’s, but also for the ageing population in general, and that in people would take years to be solved since we would need to wait until the patients were aged.”
Related news: One step closer to finding out how wine may protect your neurons
Worsened Alzheimer’s symptoms outweigh cognition benefits
The results indicate that caffeine alters the behavior of healthy mice and worsens the neuropsychiatric symptoms of mice with Alzheimer’s disease. The researchers discovered significant effects in the majority of the study variables — and especially in relation to neophobia (a fear of everything new), anxiety-related behaviors, and emotional and cognitive flexibility.
In mice with Alzheimer’s disease, the increase in neophobia and anxiety-related behaviours exacerbates their BPSD-like profile. Learning and memory, strongly influenced by anxiety, got little benefit from caffeine.
“Our observations of adverse caffeine effects in an Alzheimer’s disease 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,” says Dr. Lydia Giménez-Llort, researcher from the INc-UAB Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, and lead researcher of the project.
The results of the study form part of the PhD thesis of Raquel Baeta-Corral, first author of the article, and are the product of a research led by Lydia Giménez-Llort, Director of the Medical Psychology Unit, Department of Psychiatry and Legal Medicine and researcher at the UAB Institute of Neuroscience, together with Dr Björn Johansson, Researcher at the Department of Molecular Medicine and Surgery, Karolinska Institutet and the Department of Geriatrics, Karolinska University Hospital, Sweden, under the framework of the Health Research Fund project of the Institute of Health Carlos III.
The research is part of a special article collection on adenosine and other purinergic receptors.
Original article: 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
Corresponding author: Lydia Giménez-Llort
REPUBLISHING GUIDELINES: Open access and sharing research is part of Frontier’s mission. Unless otherwise noted, you can republish Frontiers news articles — as long as you include a link to the original research. Selling the articles is not allowed.
I want to see studies with elderly that consumed large coffee quantities during their life versus a control. Mice are good for mice !
The article is vague about the effects of caffeine in the healthy control group. Is the claim that people should stop drinking coffee once they have Alzheimer, or before then? If before, what were the negative symptoms in the control group exactly?
The conclusion of this article conflicts with other reports， I would like to see the research conclusions of the elderly.
Only one dose corresponding to 5 caps of coffee was used in this study, while lower doses where reversal hormetic effects can be observed have not been studied.
Effect of coffee was not investigated in this study, while pharmacological activity of caffeine and an extract of roasted coffee beans, where numerous other active compounds, e.g. trigonelline are present in large amounts, can have quite different effect, due to numerous interactions of molecular networks, intercellular and extra cellular signaling pathways on various levels of metabolic regulation.
The results obtained with caffeine in one high dose should not be extended on the coffee and to conclude that consumption of coffee may have negative effect on progression of Alzheimer disease
Let us be careful with preliminary conclusions based on research with mice. The title does not mention that this is experimental animal research. We are no big mice. What about a proper epidemiological study?
The researcher states that, “The mice develop Alzheimer’s disease in a very close manner to human patients with early-onset form of the disease,” This is not the main form of Alzheimer’s which develops for most people later in life.