Benzodiazepines: Alzheimer’s helpers

5. November 2014
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For a long time it has been believed that the use of benzodiazepines could increase the risk of developing Alzheimer disease. Researchers have now shown that dose and duration of treatment affect this risk. Time to rethink the prescribing of this drug class?

Dementia is a disease that pushes about 36 million of the world’s senior citizens into a state of dependence. Population growth and demographic changes allow us to expect that this number will double every 20 years. In 2050 therefore, according to forecasts by the World Health Organisation, about 115 million affected people will be living on earth.

Benzodiazepines popular with senior citizens

Already for more than ten years benzodiazepines have been suspected of having negative effects in relation to Alzheimer’s disease, or to even be complicit in its development. Nevertheless, this class of drugs is often in industrialised countries prescribed precisely to older people. “In Western countries between seven and 43 percent of seniors regularly take benzodiazepines for anxiety and sleep disorders”, write researchers from the University of Bordeaux in the British Medical Journal. The drug is used against depression.

Because of the high dependence potential of benzodiazepines, international guidelines nevertheless recommend not to exceed a treatment period of approximately four weeks. “Although the long-term effect of using this drug class for sleeping disorders is unproven and is questionable for use against anxiety, many older people resort to using them permanently”, the researchers write. But do these people also more often develop Alzheimer’s? If so, how do dosage and duration of treatment influence this risk? These questions are being pursued by the scientists from France in a retrospective study.

Impaired memory performance

Previous studies had already shown that human memory performance is impaired by the use of benzodiazepines, in that during the duration of its action the memory of the patients was greatly reduced. Whether this class of drugs also increases the risk of developing Alzheimer’s disease is still the subject of scientific discussion. In order to get to bottom of this matter, the scientists from Bordeaux evaluated data from 125,000 people over 66 years. The data was collected in Quebec, Canada, as part of a national health program.

In the evaluation of medical parameters, the researchers measured differentiation for aspects such as duration, dosage, and the use of short-term or longer-acting preparations. Since benzodiazepines may be prescribed against the signs of incipient dementia, the researchers only took into consideration those patients who had been taking the medication more than five years before the Alzheimer’s diagnosis itself.

Duration of treatment correlated with Alzheimer’s risk

During the observation period, 1,796 of the seniors developed Alzheimer’s disease. “A proportion of them well above average had taken benzodiazepines for more than three months. Their risk of developing Alzheimer’s disease was higher in comparison with the same group, which included 7,184 participants, by 43 to 51 percent”, the researchers state in relation to their results.

In particular a long period of usage and taking long-acting benzodiazepines increased the risk of seniors developing Alzheimer’s disease. This was also still the case when the scientists considered other, potentially dementia-promoting factors in their data analysis. Whether the drug class was prescribed for sleep or anxiety disorders or for depressive moods also in any case played no role.

Body of study data (almost) unequivocal

Other studies, albeit sometimes having weaknesses in their study design, had already come to similar conclusions. In addition, the working group from Bordeaux two years ago observed a similar effect among 1,063 participants with an average age of 78 years. In this prospective cohort study as well, the risk of developing Alzheimer’s within the next 15 years was increased by 50 percent if the participants had begun taking benzodiazepines.

One study, however, doesn’t stay in step with the others, as the scientists write. In 1998, researchers came to the conclusion that benzodiazepines may even protect against Alzheimer’s. “This paradoxical result can be partly explained by the fact that the reference group also included participants who had taken benzodiazepines in their past”, explain the researchers from Bordeaux.

Causal relationship not clearly proven

As the risk of developing Alzheimer’s appears to involve a dose-dependent effect, the researchers also assume a causal relationship between benzodiazepines and the outbreak of the disease. “Proving our assumption is something we nonetheless cannot do with our study”, they say, declaring their limitations. On which molecular biological processes the correlation might be based is a still open question. The researchers, however, suggest that benzodiazepines reduce the brain’s ability to compensate for damage by using alternative circuits.

Although the relationship between the use of benzodiazepines and the occurrence of Alzheimer’s is not yet fully understood, the scientists strongly advise having a rethink and evaluating the use of this drug class. As is recommended, these drugs should only be taken in the short term and in no case for more than three months.

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Medicine, Neurology

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2 comments:

Pharmacist

Aren’t sleep disturbance and anxiety both early signs of AD? Making AD patients more likely to be prescribed long-term benzos? Causal relationship far from proved.

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Martina Jansen
Martina Jansen

As sleeping problems, anxiety, mood swings etc can be early signs of Alzheimer’s disease, it is not surprising that there is a correlation between the users of these medications and those diagnosed with the disease some years later.

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