DEMENTIA – A BRIEF OVERVIEW
WHAT IS IT?
Dementia is not a single disease; it’s an overall term — like heart disease — that covers a wide range of specific medical conditions, including Alzheimer’s disease [which is the most common]. Disorders grouped under the general term “dementia” are caused by abnormal brain changes. These changes trigger a decline in thinking skills, also known as cognitive abilities, severe enough to impair daily life and independent function. They also affect behavior, feelings and relationships (Alzheimer’s Association, 2021). Dementia, it’s type and severity, can be extremely hard for a person. It can effect basic daily tasks and progress all the way to the point where you don’t recognize your own family, friends and loved ones. In addition to the hardship it places on the individual who is diagnosed, their family and friends suffer as well emotionally, physically, mentally and many times, financially. Dementia is NOT a part of normal aging and the Centers for Disease Control and Prevention (CDC) estimates there to be nearly 14 million people who suffer from dementia by 2060.
Dementia includes several cognitive disorders that are chronic, progressive, and debilitating. It can rapidly decrease the quality of life of the person with the disorder as well as those around them.
MEDICATIONS THAT MAY PLACE YOU AT RISK
There are several medications across different “classes” that have shown to have an association with increased risk of dementia. Some of the classes that have shown to have an association with developing dementia include benzodiazepines (BDZ), anticholinergics and “Z-drugs”. The main class of medications that have an association with an increased risk of developing dementia are benzodiazepines. BDZ medications include many of the common anti-anxiety medications that are prescribed to patients. These medications include diazepam (Valium), alprazolam (Xanax), clonazepam (Klonopin), lorazepam (Ativan), chlordiazepoxide (Librium), and temazepam (Restoril) among many others. BDZ medications are used for many different disorders including anxiety, panic, PTSD, insomnia, alcohol and drug withdrawal and anesthesia. Most people understand the risks associated with BDZ medication such as dependence, addiction, sedation, overdose and withdrawal. But many of the patients I’ve treated and spoken to are unaware of the risks for developing dementia when being prescribed these medications.
HOW DO THEY WORK?
Benzodiazepines slow down the activity of the central nervous system by enhancing the inhibitory effect of gamma-aminobutyric acid (GABA) in the brain, a chemical (neurotransmitter) that is used to control messages travelling from one cell to another. This decrease in activation and slowing of messages produces a calming effect in the brain, resulting in the various anti-anxiety, sedative or anti-seizure activity seen with these drugs (Therapeutic Guidelines, 2021). Newer ‘Z drugs’ (e.g. zolpidem (Ambien, Intermezzo) and zopiclone (Imovane), which also target GABA receptors, can be used to treat insomnia. Although these drugs were initially believed to have improved safety profiles compared with traditional benzodiazepines, there is increasing evidence to suggest that ‘Z drugs’ carry similar risks (The Royal Australian College of General Practitioners, 2015).
There are 3 possible mechanisms that have been presented to explain the association between benzodiazepine use and the development of dementia. Certain types of dementia, especially Alzheimer’s disease are caused by several different factors. One of the factors responsible for developing Alzheimer’s is the build of plaques in the brain called amyloid plaques. Benzodiazepines may cause a decrease in the production or activity of the enzyme responsible for eliminating or decreasing the formation of these amyloid plaques, leading to a greater accumulation over time. Additionally, there are certain cells in the brain called astrocytes near the build up of amyloid plaques which can secrete GABA causing a compounding of negative cognitive effects from BDZ medications. Finally, benzodiazepines may reduce the cognitive reserves and compensation abilities of the brain by limiting its capacity by lowering brain activation levels (Pariente, De Gage, Moore & Begaud, 2015).
WHAT DOES THE RESEARCH SAY?
Research on any topic will have many different results with conflicting information. Understanding different aspects of scientific research studies can help navigate through the plethora of information available. Although an exhaustive and detailed appraisal of all the research available was not performed by me, the majority of the reputable data point to a strong association of increased risk for developing dementia with long term use of benzodiazepine medication. One of the studies completed on the topic concluded “people who had taken a benzodiazepine for three consecutive months or less had about the same dementia risk as those who had never taken one. But those who had taken a benzodiazepine for three to six months had a 32% greater risk of developing Alzheimer’s, and those taking one for more than six months had an 84% greater risk than those who hadn’t taken one” (Harvard Health, 2015). Another study which analyzed several studies and consolidated the data showed that “long-term use of BDZ is associated with the accumulation of generalized cognitive deficits that lead to an increased risk of dementia in long-term BDZ users compared to short-term BDZ users. Withdrawal symptoms could be observed in short-term BDZ users, but no accumulation of cognitive deficits” (He, Chen, Wu, Li & Fei, 2019). Lastly, when looking at research, just like anything else, there can be bias which can alter results. Another study which analyzed several different studies and adjusted the results to control for biases that may have skewed results in previous research conducted on the topic concluded “findings indicate that the association between benzodiazepine use and dementia incidence is not purely an artefact due to protopathic bias. Reduction of inappropriate benzodiazepine prescription is likely to attenuate dementia risk (Penninkilampi & Eslick, 2018).
To be clear, there is no evidence that definitively states that any of the above mentioned medications cause dementia or that you will develop dementia. But just like there’s no evidence that states cigarettes definitively caused heart disease, we all know, and the scientific consensus is that smoking cigarettes places you at much higher risk to develop complications such as heart disease. The same concept exists between the association with certain medications and dementia.
There are many studies, and possible mechanisms by which long term use of benzodiazepines can lead to the development of dementia. All medications, benzodiazepines included, have their place and appropriate use case scenarios. These medications can be effective in relieving many problematic symptoms associated with many disorders but the inappropriate and long term use can lead to a myriad of severe and debilitating consequences. Short term use of low dose benzodiazepine medications can be safely and effectively employed for symptom relief while alternative methods for long term management are implemented. Always be aware of the risks of any medications and speak with your provider to weigh the benefits vs risks for starting or continuing any medication.
Alzheimer’s Association. (2021). What is dementia? Retrieved from https://www.alz.org/alzheimers-dementia/what-is-dementia
Centers for Disease Control and Prevention. (2019, April 05). What is dementia? Retrieved from https://www.cdc.gov/aging/dementia/index.html
Harvard Health. (2015). Two types of drugs you may want to avoid for the sake of your brain. Retrieved from https://www.health.harvard.edu/mind-and-mood/two-types-of-drugs-you-may-want-to-avoid-for-the-sake-of-your-brain
He, Q., Chen, X., Wu, T., Li, L., & Fei, X. (2019). Risk of dementia in long-term benzodiazepine users: Evidence from a meta-analysis of observational studies. Journal of Clinical Neurology, 15(1), 9. doi:10.3988/jcn.2019.15.1.9
Pariente, A., De Gage, S. B., Moore, N., & Bégaud, B. (2015). The benzodiazepine–dementia disorders link: Current state of knowledge. CNS Drugs, 30(1), 1-7. doi:10.1007/s40263-015-0305-4
Penninkilampi, R., & Eslick, G. D. (2018). A systematic review and meta-analysis of the risk of DEMENTIA associated with Benzodiazepine use, after controlling for Protopathic Bias. CNS Drugs, 32(6), 485-497. doi:10.1007/s40263-018-0535-3
The Royal Australian College of General Practitioners. (2015). Prescribing drugs of dependence in general practice, part b. Retrieved from https://www.racgp.org.au/FSDEDEV/media/documents/Clinical%20Resources/Guidelines/Drugs%20of%20dependence/Prescribing-drugs-of-dependence-in-general-practice-Part-B-Benzodiazepines.pdf
Therapeutic Guidelines. (2021). Etg complete: Therapeutic guidelines. Retrieved from https://tgldcdp.tg.org.au/etgcomplete