In the global effort to understand the causes of Alzheimer's disease, another culprit emerges: Benzodiazepines. This class of drugs includes the widely prescribed anti-anxiety medications Ativan (lorazepam), Xanax (Alprazolam), Valium (diazepam), and Klonopin (Clonazepam). Researchers from France and Canada report in The BMJ that prolonged use of the drugs - for three months or more - may significantly increase the risk of Alzheimer's disease years later. The drugs have been associated with short-term cognitive impairment, but the connection to Alzheimer's has been less clear. Now, the new study finds a convincing, and apparently strong, link between benzodiazepines and Alzheimer's disease.
At present, 5 million people in the U.S. suffer from Alzheimer's disease alone, according to the Alzheimer's Association, and the number is expected to more than triple by 2025. Worldwide, the numbers are even more startling: 36 million are affected globally, and by 2050, it's projected to rise to 115 million.
In the current study, the researchers looked at the health records of almost 1,800 elderly residents of a community living facility in Quebec who had recently been diagnosed with Alzheimer's disease, and over 7,100 healthy controls. They looked at whether the participants had taken benzodiazepines in the past - specifically in the 5 to 10 year window preceding the diagnosis.
People who had taken the drugs for at least three months had a 50% higher risk of having been diagnosed with Alzheimer's. Those who took benzodiazepines for six months had an almost double risk of an Alzheimer's diagnosis. The relationship worked in a dose-dependent manner, meaning that the longer a person took the medications or the higher the dose, the higher the risk of developing Alzheimer's. Longer-acting forms of the drugs were also linked to a greater Alzheimer's risk than shorter-acting forms. The results held true even when the authors adjusted for symptoms like anxiety, depression, and sleep problems, which are often symptoms of dementia.
It's not totally clear why the connection exists biologically, but researchers do know that the short-term cognitive effects of benzodiazepines may be due to changes in the signaling of a neurotransmitter called GABA. 'The short-term deleterious effects of benzodiazepine on memory are well documented,' study author Sophie Billioti de Gage said in an email. 'They are mediated though an agonist action on receptors of gamma-aminobutyric acid [GABA], a major inhibitory neurotransmitter in the brain.'
She adds that another clue to what's going on is that researchers have found reductions in the density of benzodiazepine receptors in people who died of Alzheimer's. 'The reduction in the number of benzodiazepine receptors has been observed comparing brains obtained at autopsy from individuals with Alzheimer's disease and healthy individuals. Whether or not this observation can explain a biological mechanism linking benzodiazepine and Alzheimer disease is unclear.'
The cognitive reserve theory may also play in: People who use benzodiazepines over the long term may have neurological changes that deplete their cognitive reserve, reducing the brain's ability to cope with and compensate for early Alzheimer's symptoms.
One concern with studies like this is that reverse causation is at play: It could be that people who are already showing early symptoms of Alzheimer's - like anxiety, depression, insomnia - are taking benzodiazepines to treat those symptoms. So it's more that early effects of Alzheimer's disease 'caused' the use of the benzodiazepines, instead of the other way round. But the authors intentionally omitted the five years directly before the Alzheimer's diagnosis. Instead, they looked at an earlier time period - five to 10 years preceding it. For this reason, and the dosing reasons mentioned above, they say it's more likely that there is, in fact, a causal relationship going on, where long-term benzodiazepine use may actually trigger Alzheimer's pathology.
How big a role benzodiazepines play is unclear. But the authors conclude that while benzodiazepines are 'indisputably valuable tools for managing anxiety disorders and transient insomnia,' they shouldn't be used for longer than three months.
At present, upwards of 50% of older people use the medication for some kind of mental health problem. The American Geriatrics Society has included benzodiazepines on its list of inappropriate drugs for seniors. It may be time for doctors to listen to this recommendation.
Posted by Unknown on Wednesday, September 10, 2014 - Rating: 4.5
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