Summary: A new study reports caffeine may worsen neuropsychiatric symptoms associated with Alzheimer’s disease. Caffeine, researchers report, exacerbates neophobia, anxiety and cognitive flexibility in mouse models of the disease.
Source: UAB.
It is well known that memory problems are the hallmark of Alzheimer’s disease. However, Alzheimer’s is also characterised by neuropsychiatric symptoms, which may be strongly present in the first stages of the disease. Known as Behavioural and Psychological Symptoms of Dementia (BPSD); anxiety, apathy, depression, hallucinations, and paranoia are part of an array of symptoms which manifest in different manners depending on the individual patient. They are considered the strongest source of distress for patients and caregivers.
Caffeine has recently been suggested as a strategy to prevent dementia, both in patients with Alzheimer’s disease and in normal aging processes, due to its action in blocking adenosine receptors, which may cause dysfunctions and diseases in old age. However, there is some evidence that once the cognitive and NPS symptoms are developed, caffeine may exert opposite effects.
To address these issues, a study was conducted with normal aging mice and familial Alzheimer’s animal models. “The mice develop Alzheimer’s disease 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”, explains Raquel Baeta-Corral, first author of the atudy.
“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 a very low dose 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”, explains Dr Björn Johansson, researcher and physician at the Karolinska University Hospital. The research was conducted from the onset of the disease up to more advanced stages, as well as in healthy age-matched mice.
The results indicate that caffeine alters the behaviour of healthy mice and worsens the neuropsychiatric symptoms of mice with Alzheimer’s disease. The researchers discovered significant effects in the majority of variables studies, especially in relation to neophobia (a fear of everything new), anxiety-related behaviours; 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 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*.
Source: Lydia Giménez-Llort – UAB
Publisher: Organized by NeuroscienceNews.com.
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Original Research: Open access research for “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” by Raquel Baeta-Corral, Björn Johansson, and Lydia Giménez-Llort in Frontiers in Pharmacology. Published February 15 2018.
doi:10.3389/fphar.2018.00079
[cbtabs][cbtab title=”MLA”]UAB “Long Term Caffeine Use Worsens Alzheimer’s Symptoms.” NeuroscienceNews. NeuroscienceNews, 1 April 2018.
<https://neurosciencenews.com/caffeine-alzheimers-8722/>.[/cbtab][cbtab title=”APA”]UAB (2018, April 1). Long Term Caffeine Use Worsens Alzheimer’s Symptoms. NeuroscienceNews. Retrieved April 1, 2018 from https://neurosciencenews.com/caffeine-alzheimers-8722/[/cbtab][cbtab title=”Chicago”]UAB “Long Term Caffeine Use Worsens Alzheimer’s Symptoms.” https://neurosciencenews.com/caffeine-alzheimers-8722/ (accessed April 1, 2018).[/cbtab][/cbtabs]
Abstract
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
Coffee or caffeine has recently been suggested as prophylaxis for dementia. Although memory problems are hallmarks of Alzheimer’s disease, this dementia is also characterized by neuropsychiatric symptoms called Behavioral and Psychological Symptoms of Dementia (BPSD). The impact of preventive/therapeutic strategies on both cognitive and non-cognitive symptoms can be addressed in the 3xTg-AD mice, since they exhibit cognitive but also BPSD-like profiles. Here, we studied the long-term effects of a low dose of caffeine in male 3xTg-AD mice and as compared to age-matched non-transgenic (NTg) counterparts with normal aging. Animals were treated (water or caffeine in drinking water) from adulthood (6 months of age) until middle-aged (13 months of age), that in 3xTg-AD mice correspond to onset of cognitive impairment and advanced stages, respectively. The low caffeine dosing used (0.3 mg/ml) was previously found to give a plasma concentration profile in mice roughly equivalent to that of a human coffee drinker. There were significant effects of caffeine on most behavioral variables, especially those related to neophobia and other anxiety-like behaviors, emotionality, and cognitive flexibility. The 3xTg-AD and NTg mice were differently influenced by caffeine. Overall, the increase of neophobia and other anxiety-related behaviors resulted in an exacerbation of BPSD-like profile in 3xTg-AD mice. Learning and memory, strongly influenced by anxiety in 3xTg-AD mice, got little benefit from caffeine, only shown after a detailed analysis of navigation strategies. The worsened pattern in NTg mice and the use of search strategies in 3xTg-AD mice make both groups more similar. Circadian motor activity showed genotype differences, which were found to be enhanced by caffeine. Selective effects of caffeine on NTg were found in the modulation of behaviors related to emotional profile and risk assessment. Caffeine normalized splenomegaly of 3xTg-AD mice, a physical indicator of their impaired peripheral immune system, and trended to increase their corticosterone levels. 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.
