Benzodiazepine use and risk of incident dementia or cognitive decline

Benzodiazepines are commonly prescribed for the treatment of insomnia and anxiety. Approximately 9-12% of older adults in the United States report to be using benzodiazepines. These medications are associated with deleterious effects such as falls, fractures, and delirium. Furthermore, previous single dose studies have shown that benzodiazepines impair aspects of cognition, such as memory and attention. Some studies suggest that long term use of benzodiazepines do not increase the risk of cognitive decline, but the results are conflicting. Thus,the objective of this research study is to determine whether higher use of benzodiazepines is associated with a higher risk of dementia or more rapid cognitive decline.

The cognitive abilities screening instrument (CASI) was administered every two years to screen for dementia and was used to examine cognitive trajectory. In addition, every two years the  cognitive function, collect demographic characteristics, health behaviors, and health status of patients are examined. Incident dementia and alzheimer’s disease were determined. At the end of the study, 797 participants  (23.2%) developed dementia, and 637 of them developed alzheimer’s disease. The risk of dementia was only slightly higher in people with minimal exposure to benzodiazepines but not with the highest level of exposure. The low risk observed may represent treatment of prodromal symptoms. Overall, this pattern does not support a causal relationship between benzodiazepine use and risk of dementia.

This study was particularly interesting because there has already been several research articles that have found a relationship between benzodiazepines and dementia. Despite that, these researchers still pursued this topic because they observed conflicting results in multiple studies. With this knowledge, patients may feel relieved to find out that benzodiazepines will not cause a decline in cognitive function. Do you think it is important to develop research projects that focus on topics that were addressed in the past? Why or why not?
Gray SL, Dublin S, Yu O, et al. Benzodiazepine use and risk of incident dementia or cognitive decline: a prospective population based study. BMJ. 2016;352:i90

Effects of Prescription Drug Reduction on Quality of Life in Community Dwelling Patients with Dementia

Due to the rapid aging of Japanese society, community-dwelling medical care has become a social necessity. In this study, researchers focused on patients over 65 years of age with dementia. Approximately 4.62 million Japanese elders over the age of 65 suffer from dementia, and the morbidity rate associated with dementia is 15%. The goal of these researchers is to find methods that allow elderly people, including dementia patients to lead high-quality lives.

Community-dwelling medical care consists primarily of drug therapy. Thus, problems associated with polypharmacy are expected to increase. The use of multiple drugs and diminished cognitive function may cause the elderly to experience problems using drugs appropriately. Patients with six or more drugs have been reported to show a higher incidence of adverse drug reactions than other patients. Japanese researchers decided to study whether drug reduction in community-dwelling dementia patients would change the quality of life and the activities of daily living three to six months after the drug reduction.

Researchers studied 50 community-dwelling patients ages 65 or older, and the number of prescription drugs taken by each patient was reduced by an average of 2.6. In the intervention group with reduction in medications, researchers found that the scores associated with quality of life remained stable and scores related with activities of daily living slightly increased. There were also significant increases in items related to activities of daily living, such as transferring to bed, walking, and bladder control. However, there were worsened scores for anxiety/depression questions. This may have been due to the reduction of use of benzodiazepines.

Since there were results that were associated with an increase in activities of daily life, I believe that it would be a good idea to conduct more research on drug reduction. It would be interesting to see if other studies had stronger evidence about the benefits of drug reduction. In addition, I think it would be a good idea to learn about when drug reduction may be appropriate in a clinical setting. What is your opinion about drug reduction? Do you believe that this is an important topic that must be researched?

Sakakibara M, Igarashi A, Yoshimasa T et al. Effects of Prescription Drug Reduction on Quality of Life in Community-Dwelling Patients with Dementia. J Pharm Pharm Sci. 2016;18(5): 705-712

Using Medication Adherence as an Indicator of Cognitive Dysfunction Among the Elderly

Anyone who has been required to take a medication on a daily basis can attest to the fact that it is very easy to forget or skip a dose. Imagine having to remember to take 6 or 7 medications everyday at different times of the day. This undoubtedly requires a certain level of cognitive ability and a clear mind to be able to organize all of one’s medications and to proceed to remember to take them. While one can usually stay adherent to his medications if some sort of system is set up for him, a decline in cognitive function and the development of dementia may nullify all efforts to keep track of and remain adherent to his medications.

This study assesses the possibility of using medication adherence as an indicator of the development of cognitive dysfunction in elderly individuals. This was a retrospective cross-sectional study, which examined 3351 Japanese patients with a mean age of 78.9 years old. Participants completed a comprehensive cognitive function test and got their medication use checked by clinical pharmacists. The Lawton’s instrumental activities of daily living (IADLs) scale assessed participants’ abilities to carry out self-care tasks in 8 categories such as the ability to use a telephone, transportation use, ability to handle finances, and responsibility for own medications. The Barthel Index score assessed another 10 self-care categories and the MMSE (Mini-Mental State Examination) measured participants’ orientation in time and space, attention, memory, language, and constructive skills.

The results of this study demonstrated that those in the early stage of cognitive failure were unable to perform activities of daily living (ADLs) in the “shopping” and “responsibility for own medications” categories. Moreover, the data from this study showed that there was a significant association between poor medication adherence and many other factors such as the use of Alzheimer’s disease medication, advanced age, and low Barthel index scores. Of the 3351 patients in this study, 2753 had some sort of cognitive dysfunction, and almost all patients diagnosed with dementia demonstrated a lower adherence to their medications in this study.

This study reveals that IADL scores are an effective method of predicting cognitive dysfunction in elderly individuals. Medication adherence and the development of dementia are both extremely important issues that require immediate attention. Pharmacists can play a huge role in caring for the elderly by providing screenings to measure for cognitive dysfunction and, in doing so, monitoring the elderly’s medication adherence as well.

Mizokami F, Mase H, Kinoshita T, et al. Adherence to Medication Regimens is an Effective Indicator of Cognitive Dysfunction in Elderly Individuals. Am J Alzheimers Dis Other Demen. 2016; 31(2):132-36

Proton Pump Inhibitors May Increase the Risk of Dementia in the Elderly Population

Proton pump inhibitors (PPIs) are a class of medications that are commonly used in the elderly population to remedy gastrointestinal problems. This prospective cohort study in German  looks at the possible association between these medications and dementia. For the study, the inclusion criteria was at least 75 years old and no diagnosis of dementia. They defined the use of a PPI as having one prescription per quarter of the following medications: omeprazole, pantoprazole, lansoprazole, esomeprazole, or rabeprazole. Patients who only used PPIs occasionally were not included in the study.  This study also worked to analyze other factors that could contribute to the risk of dementia. Some of these factors were gender, the use of multiple prescription medications, stroke, and comorbid diagnosis with conditions such as depression, heart disease, or diabetes. The data analyzed was from 2004 – 2011.

A total of 73,679 people who met the inclusion criteria were analyzed in the study. The results of the study shows that the use of PPIs in the elderly is associated with an increased risk of dementia.  77.9% of patients who took PPIs regularly during this study had a “significantly increased risk of incident dementia”.  The study results also show that males had a higher risk of dementia with use of PPIs. The comorbid diagnosis of depression and stroke had a higher risk of dementia with the use of PPIs. Comorbid diagnosis with diabetes and the use of other prescription medication with PPIs showed a very slight increased risk of dementia. Patients using PPIs with heart disease actually had a slight decreased risk in developing dementia.

This study is important because PPIs are such a commonly used medication class, especially in the elderly population. If these medications are contributing to the onset of dementia, consideration should be given to avoid prescribing this medication in the elderly population. Additionally, this study could eventually lead to a clearer understanding of how disease states such as dementia or Alzheimer’s develop in the first place. From there, we could focus on developing medications that could help to prevent and treat these terrible conditions.

Gomm W, von Holt K, Thomé F, et al. Association of Proton Pump Inhibitors With Risk of Dementia. JAMA Neurol. doi:10.1001/jamaneurol.2015.4791. (Published 15 February 2016).

Association of Proton Pump Inhibitors with Risk of Dementia

Proton pump inhibitors, or PPIs, are medications used to treat gastrointestinal diseases such as acid reflux (GERD). These medications are commonly prescribed to patients in the community, and even more take their over-the-counter counterparts. This article describes a study done to measure the correlation of the use of PPIs with cognitive decline in older adults. The study analyzed data from a German health insurer to determine the association between patients 75 years or older who had prescribed PPIs such as omeprazole, pantoprazole, lansoprazole, esomeprazole, and rabeprazole and diagnoses of incident dementia from August to November 2015. The study also adjusted for confounding factors such as age, sex, comorbidities, and prescription of other medications. The study found that patients regularly taking PPIs had a significantly increased risk of incident dementia compared to patients not taking PPIs. The study concluded that not taking PPIs may decrease the risk of dementia onset, possibly because the use of PPIs has been associated with increased beta amyloid levels in the brains of mice (a characteristic of dementia patients), which may translate to having the same effects in humans.

Dementia is a health problem that pharmacists will continue to face with increasing frequency, especially as the baby boomer generation reaches the ages when the onset of dementia normally occurs. Since this disease state is one that also puts an extreme burden on the family and caregivers of dementia patients, it is imperative to identify its causes so that its onset can be prevented. I am very interested in seeing further studies done on the correlation between PPIs and dementia, as well the correlation of its onset with other frequently prescribed medications. What do you think the pharmacist’s role in patient education of this new finding will be, and how do you think it will affect the pharmacist’s job in the future?

Gomm W, von Holt K, Thomé F et al. Association of Proton Pump Inhibitors with Risk of Dementia. JAMA Neurol. doi:10.001/jamaneurol.2015.4791 (published 15 February 2016).

Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study

A study investigated the use of benzodiazepines the risk of it causing dementia or rapid cognitive decline. Benzodiazepines are used among 9-12% of older adults in the United States to treat anxiety and insomnia. Drugs that fall into this class are not recommended for long term use in older adults due to the associated increased risk of falls and delirium. Single dose studies found that benzodiazepines impair memory and attention span, but its effect in long term use is still uncertain. One problem with determining if long term benzodiazepine use increases the risk of dementia is that dementia is often preceded by anxiety and insomnia: symptoms often treated with benzodiazepines. Two out of three known studies that considered early dementia symptoms and potential for reverse causation reported an increased risk of dementia with benzodiazepine use.

The investigators hypothesized that cumulative, heavier benzodiazepine exposure over a long period of time was the most likely mechanism to cause an increased risk of dementia. The study was conducted within an integrated healthcare delivery system in the North West US. There were 3434 randomly selected participants in the study aged 65 or older who did not have dementia at the start of the study. Every two years, the cognitive abilities screening instrument (CASI) was administered to test for dementia. It was also used to assess cognitive trajectory. Computerized pharmacy data was use to define benzodiazepine exposure associated with risk of dementia. This consisted of the total standardized daily doses (TSDDs) over a 10 year period. The date of onset dementia was made the midpoint between the visit triggering the dementia evaluation and the visit before that.

While the study found a slightly higher risk of dementia associated with the lowest use of benzodiazepine, it did not find an increased risk in those using the highest level. Therefore, the findings do not support the theory that cumulative use of benzodiazepines at levels used in our population has a causal relationship to increased risk of cognitive decline or dementia. However, the study did not investigate acute adverse cognitive effects that can occur upon starting benzodiazepine treatment in older adults. Healthcare providers should still avoid benzodiazepine use in older adults to prevent other important adverse effects. Considering that other studies did report a causal relationship, it seems that this is a topic that still requires more investigation.

Gray GL, Dublin S, Yu O, et al. Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study. BMJ. 2016;352:90.

Potentially inappropriate anticholinergic medication use in older adults with dementia

This was a cross-sectional study done to assess the prevalence of inappropriate anticholinergic medication use in elder dementia patients.  The study used the American Geriatrics Society Beers criteria as guidelines for what medications were considered as potentially inappropriate to use.  This study was published in 2015, however, the data used was from a 2009-2010 national representative health care utilization survey called MEPS.  The MEPS data showed that about 3.78 million adults 65 years old and older were diagnosed with dementia.  Out of those diagnosed with dementia, 1.02 million adults (26.95%) were on potentially inappropriate anticholinergic medications.  The analysis was then further broken down to examine the percentage of patients with dementia over 65 years old who were also diagnosed with either mood disorders (17%) or anxiety (15%).  The conclusion drawn included that those with mood disorders or anxiety had an increased chance of inappropriate anticholinergic medication use, while those 75 to 84 years old had a decreased risk.

The most frequently found medication that could possibly cause inappropriate anticholinergic medication use, according to American Geriatrics Society Beers criteria, was oxybutynin.  Oxybutynin had been found to be the inappropriate medication 16.8% of the time, while solifenacin closely followed at 16.6%.  Some of the other medications often found were paroxetine, tolterodine, promethazine, and cyclobenzaprine.  The geriatric population with dementia already has an increased sensitivity to anticholinergic activity, and therefore this article recommends that anticholinergic medications should be minimized or avoided completely if possible.

Overall, this is an important article because we, as future pharmacists, have to be aware, and stay alert for recommendations such as the avoidance/minimization of the use of anticholinergic medications in dementia patients.  With the geriatric population on the rise, how could studies like this impact pharmacy medication interaction screenings?

J Am Pharm Assoc. 2015;55(6):603-612.