Common sleeping tablets and anxiety drugs taken by millions of patients has been linked to a 50 per cent increased risk of Alzheimer’s disease, researchers have found.
Taking the drugs known as benzodiazepines, which include diazepam and lorazepam, for three months or more was linked with a greater chance of being diagnosed with Alzheimer’s disease five years later.
At least six million prescriptions were issued for the drugs in England last year and the researchers said the findings are important because of the large numbers of older people taking the medicines.
Researchers behind the study described the findings as being of “major importance for public health”.
They warned that although it cannot be definitively proven that the drugs are causing Alzheimer’s there is a strong ‘suspicion of possible direct causation’.
The drugs should be not be taken for more than three months in light of these findings, the researchers said.
However, other experts said the results may reflect that people who are already in the early stages of Alzheimer’s are often treated for sleep problems and anxiety and this is confusing the findings.
In a research paper published in the British Medical Journal, scientists from the University of Bordeaux and the Univeristy of Montreal beind the latest study said their findings were especially important “considering the prevalence and chronicity of benzodiazepine use in elderly populations and the high and increasing incidence of dementia in developed countries.”
They said: “It is now crucial to encourage physicians to carefully balance the benefits and risks when initiating or renewing a treatment with benzodiazepines and related products in elderly patients.”
The French and Canadian researchers examined data from Quebec from a period of at least six years and identified 1,796 cases of Alzheimer’s disease which where then individually matched with 7,184 healthy people matched for age, sex, and duration of follow-up.
They found that past use of benzodiazepines was associated with a 51 per cent increased risk fo Alzheimer’s disease. The link was stronger with longer exposure to the drugs or use of long-acting versions of the medicines.
In an accompanying editorial Professor Kristine Yaffe of the University of California at San Francisco and Professor Malaz Boustani of the Indiana University Centre for Aging Research, said that in 2012 the American Geriatrics Society included benzodiazepines in a list of drugs that should not be used in older people because of the side effects of brain function.
Dr Liz Coulthard, Consultant Senior Lecturer in Dementia Neurology at University of Bristol, said: “This work provides yet another reason to avoid prescription of benzodiazepines for anything other than very short term relief of insomnia or anxiety.
“In addition to short term cognitive impairment, falls and car accidents already known to be associated with benzodiazepine use, there is a hint from this study that these drugs might in some way increase the risk of developing Alzheimer’s disease.
“However, we know that Alzheimer’s disease pathology accumulates for up to 17 years prior to diagnosis and this study looked at benzodiazepine use well into the course of the pathological cascade in the disease.
“In addition, retrospective studies such as this cannot prove causation. Therefore there is still a possibility that, rather than causing Alzheimer’s disease, benzodiazepines tend to be prescribed to patients presenting with anxiety or insomnia as part of an as yet undiagnosed dementia.”
Prof Gordon Wilcock, Emeritus Professor of Geratology at University of Oxford, said: “This carefully conducted study provides convincing evidence that the use of benzodiazepines may contribute to the development of Alzheimer’s disease, and importantly may be another factor we could modify to reduce the occurrence of dementia.
“However, these drugs would have been given to treat symptoms and it is possible that the latter may have been the earliest signs of unrecognised Alzheimer’s disease, although the authors have tried to control for this as far as was possible in their study.
“Ideally more research needs to be undertaken, but it will be difficult to do this prospectively as most clinicians would avoid long term prescription of these drugs in older people.”
Dr James Pickett, head of research at Alzheimer’s Society, said: “With 1.5million people in the UK being prescribed benzodiazepines at any one time, evidence that their long-term use increases the risk of dementia is significant, and raises questions about their use.
“This research should not be used to condemn benzodiazepines completely, since their short-term use can have an important role in the management of anxiety and insomnia, but people and doctors should be aware of the longer-term risks associated with these drugs.”
“This report comes the day before the G7 Global Dementia Legacy Event in Canada where leaders will discuss how we tackle dementia through research. There are currently 850,000 people living with dementia in the UK, and with so few drugs available to treat Alzheimer’s disease, these findings show the need for us to look at how we might change prescription habits to reduce people’s risk of developing dementia.”
Prof Guy Goodwin, President of the European College of Neuropsychopharmacology, said: “Many treatments can look bad because they are given to sick people. This is “confounding by indication”, and is the bane of all epidemiological studies of drug exposure. This publication recognises the problem but may not have an adequate solution.
“The finding that benzodiazepine exposure is associated with the diagnosis of Alzheimer’s disease five years or more later could mean that the drugs cause the disease, but is more likely to mean that the drugs are being given to people who are already ill. In other words, we are seeing an association, rather than a cause.
“Non-specific symptoms arise in the 14 years before an Alzheimer diagnosis, so a five year study, as in this paper, may not be long enough to exclude what we call reverse causality; in other words symptoms in the early phases of Alzheimer’s disease may increase the probability of being prescribed a benzodiazepine.
“It is very difficult to control for this in most databases because the detail is insufficient to reconstruct the clinical reality.
“Nevertheless, benzodiazepines can impair memory by their direct effect on the brain (unrelated to dementia), and their use in the elderly always merits caution and care to balance side-effects with benefits.”
Prof John Hardy, Professor of Neuroscience at University College London, said: “The apparent association between benzodiazepines and Alzheimer’s disease is interesting and deserves further investigation.
“There are many possible explanations: it could be a true association in that it reflects benzodiazepine use in the early stage of disease (this is the reverse causation discussed by the authors), it could be caused by benzodiazepine causing minor brain damage which is clinically additive to Alzheimer disease, there could be a direct relationship between benzodiazepine drug action and the disease process, or it could be a false positive, a statistical fluke.
“Clearly more work is needed before any firm conclusions are drawn. Clinicians are already careful about benzodiazepine prescribing so I would not regard this unexplained and as of yet unreplicated study as cause for any alarm.”