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Long-term use of pills for anxiety and sleep problems may be linked to Alzheimer's
Posted: Wednesday, September 10, 2014 3:45 PM
Joined: 12/6/2011
Posts: 3326

Taking benzodiazepines -- widely prescribed drugs to treat anxiety and insomnia -- is associated with an increased risk of developing Alzheimer's disease, particularly for long-term users, suggests a new study. 

The researchers warn that unwarranted long-term use should be considered a public health concern. Dementia currently affects about 36 million people worldwide and this number is expected to double every 20 years, reaching 115 million by 2015. Although a increased risk of dementia has been identified in benzodiazepine users, the nature of this association, whether causal or not, remains unclear. 


So a team of researchers based in France and Canada set out to investigate the relationship between the risk of Alzheimer's disease and benzodiazepine exposure over a several years, as well as a potential dose-response relationship. 


Using data from the Quebec health insurance program database (RAMQ), they tracked the development of Alzheimer's disease in a sample of elderly residents living in Quebec, Canada who had been prescribed benzodiazepines. 


Over a period of at least six years, they identified 1,796 cases of Alzheimer's disease. They then compared each case with 7,184 healthy people matched for age, sex, and duration of follow-up. 


Results show that past use of benzodiazepines for three months or more was associated with an increased risk (up to 51%) of Alzheimer's disease. The strength of association increased with longer exposure and with use of long-acting benzodiazepines rather than short-acting ones. 


Further adjustment for symptoms that might indicate the start of dementia, such as anxiety, depression or sleep disorders, did not meaningfully alter the results. 


In this large case-control study, benzodiazepine use was associated with an increased risk of Alzheimer's disease, say the authors. They emphasise that the nature of the link is still not definitive, but say the stronger association seen with long-term exposures "reinforces the suspicion of a possible direct association, even if benzodiazepine use might also be an early marker of a condition associated with an increased risk of dementia." 


Benzodiazepines are "indisputably valuable tools for managing anxiety disorders and transient insomnia" they write, but warn that treatments "should be of short duration and not exceed three months." 


They conclude that their findings are of "major importance for public health, especially considering the prevalence and chronicity of benzodiazepine use in elderly populations and the high and increasing incidence of dementia in developed countries." 


In view of the evidence, they conclude that "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." 


In an accompanying editorial, Professor Kristine Yaffe of the University of California at San Francisco and Professor Malaz Boustani of the Indiana University Center for Aging Research, point out that in 2012 the American Geriatrics Society updated its list of inappropriate drugs for older adults to include benzodiazepines, precisely because of their unwanted cognitive side effects. 


Yet almost 50% of older adults continue to use these drugs, they say. And without any formal monitoring system, the potential long term consequences on brain health are likely to be missed, adding to the growing prevalence of cognitive impairment among older people, they suggest.


Given the expanding numbers of older people likely to be treated with several drugs at a time, and/or who are at risk of Alzheimer's disease, this gap needs to be plugged, they say. 


  1. S. Billioti de Gage, Y. Moride, T. Ducruet, T. Kurth, H. Verdoux, M. Tournier, A. Pariente, B. Begaud. Benzodiazepine use and risk of Alzheimer's disease: case-control study. BMJ, 2014; 349 (sep09 2): g5205 DOI: 10.1136/bmj.g5205 
  2. K. Yaffe, M. Boustani. Benzodiazepines and risk of Alzheimer's disease. BMJ, 2014; 349 (sep09 6): g5312 DOI: 10.1136/bmj.g5312 



Lane Simonian
Posted: Wednesday, September 10, 2014 11:37 PM
Joined: 12/12/2011
Posts: 4854

Here is some evidence for a causal link between benzodiazepines and Alzheimer's disease rather than a correlation or complete reverse causation (some people with anxiety are in the pre-dementia phase of the disease).

 2003 Feb;37(2):334-42.

Benzodiazepine-induced protein tyrosine nitration in rat astrocytes.

And from another article:

Tyrosine nitration is one of the earliest markers found in Alzheimer's disease brains, in the plaques of multiple sclerosis brains, and in degenerating upper and lower neurons motor neurons in amyotrophic lateral sclerosis (ALS) patients.

Peroxynitrites mediate most tyrosine nitration in neurodegenerative diseases.

It may be a combination effect.  Stress makes people more prone to dementia which leads to the taking of benzodiazepines which increases the risk of dementia even more.

Lane Simonian
Posted: Thursday, September 11, 2014 12:09 AM
Joined: 12/12/2011
Posts: 4854

In a way, this study links psychological stress to oxidative damage in the brain and suggests that herbal antioxidants may protect against this. 



Distress-mediated tissue oxidative stress was examined as a model of sub-healthy condition defined in traditional Chinese medicine theory. Mice were subjected to psychologically stressful conditions by whiskers removal. Under this condition, spontaneous locomotive activity was significantly enhanced in the dark (P < 0.05 versus the control mice in three different movements), and granulocytes/lymphocytes balance shifted to granulocytes. At the same time, peroxynitrite level in blood plasma.  increased to ∼180% from that of the control mice at 6 h after removal of the whiskers (P < 0.01), and was maintained even after 12 h. Both protein carbonyl formation and lipid peroxidation were significantly increased under this condition in brain, heart, liver and spleen at 6 h after removal of whiskers (P < 0.05 or P < 0.01), and these levels were maximized after 12 h (increased to 120–160%, P < 0.05 or P < 0.01). The oxidative tissue injuries observed at 12 h after the removal of the whiskers were effectively prevented by two traditional Chinese medicine formula: Shengmai San (SMS) and Ling Gui Zhu Gan Tang (LGZGT), when administered for 5 days before the removal of the whiskers. Therefore, this stress model is considered useful in assessing the preventive potential of antioxidants and antioxidant-based herbal mixtures in treating the pathophysiology associated with psychological or emotional distress. 


Other than thinking about the trauma of whiskers being removed from mice this study is useful. 

Posted: Friday, September 26, 2014 12:44 AM
Joined: 9/25/2014
Posts: 1

I am new to alz connected and newly diagnosed with alz at 43. I have had depression and anxiety and for years and have been prescribed clonazepam for years to help me sleep.  I also found out last year when I did my first sleep study ever, that I have severe obstructive sleep apnea, which being a single guy, unfortunately it has gone on for years.  I feel like both of these things might have contributed to my diagnosis and to it happening so young.  Has anyone else experienced any of these problems?  Thanks. 



Iris L.
Posted: Friday, September 26, 2014 1:25 AM
Joined: 12/15/2011
Posts: 16705

Welcome, Chris.  Both depression and anxiety and sleep apnea can mimic dementia.  Did you have the  6 hour neurocognitive testing?  Did you have blood work to rule out medical disorders?  Did you have any imaging studies?  

Two suggestions:  read "The Alzheimer's Action Plan" by Doraiswamy and Gwyther to learn what is included in making a diagnosis.  Also, read about pseudodementia.

Please join us patients on the Younger Onset board for more support.  It may be possible that you do have dementia.  There are others in your age group.  We support each other.

Iris L.

Posted: Friday, September 26, 2014 10:37 AM
Joined: 9/12/2013
Posts: 3579

Chris - glad you found message boards...


I took Ativan for 10 years as needed, lowest dose but insomnia was horrible and so was anxiety. I did live a better life with medication.


After a casual reference from Internist that "maybe the Ativan is making you lethargic" and reading about these drugs connection to ALZ I decided to cut back the Ativan.


I have started using Medical Marijuana to sleep and for day time anxiety. I also use Lemon Balm Melissa Leaves capsules which are very effective and do not slow me down physically. Although I still use Ativan for a bad siege of insomnia and am grateful for it, I think it does make me less active. Less active = lower cognitive ability.


If you slowly taper off your medication you would be able to note if your thinking clears.


Right now I am feeling more cogent than 8 months ago but my circumstances have changed for the better. Now that we know much of the "anxiety" was from ALZ changes and I continue to let go of the shock anger and grief, my abilities are more stable.


Please let us know your thoughts on anxiety and your brain function. This is important for us to understand the trade offs in taking mainstream pharmaceuticals. Whatever you can do to reduce that feeling of tension will lead to improvements in your thinking.

Love and Courage

Posted: Friday, September 26, 2014 11:48 PM
Joined: 12/6/2011
Posts: 3326

Want to add my welcome, too. Hope you will find that the dementia you're experiencing is caused by something that is curable or treatable.