Editorial : Deprescribing and Minimizing Use of Anticholinergic Medications

Peer reviewedPublisher PD

Usability and feasibility of consumer-facing technology to reduce unsafe medication use by older adults

Background Mobile health technology can improve medication safety for older adults, for instance, by educating patients about the risks associated with anticholinergic medication use. Objective This study's objective was to test the usability and feasibility of Brain Buddy, a consumer-facing mobile health technology designed to inform and empower older adults to consider the risks and benefits of anticholinergics. Methods Twenty-three primary care patients aged ≥60 years and using anticholinergic medications participated in summative, task-based usability testing of Brain Buddy. Self-report usability was assessed by the System Usability Scale and performance-based usability data were collected for each task through observation. A subset of 17 participants contributed data on feasibility, assessed by self-reported attitudes (feeling informed) and behaviors (speaking to a physician), with confirmation following a physician visit. Results Overall usability was acceptable or better, with 100% of participants completing each Brain Buddy task and a mean System Usability Scale score of 78.8, corresponding to “Good” to “Excellent” usability. Observed usability issues included higher rates of errors, hesitations, and need for assistance on three tasks, particularly those requiring data entry. Among participants contributing to feasibility data, 100% felt better informed after using Brain Buddy and 94% planned to speak to their physician about their anticholinergic related risk. On follow-up, 82% reported having spoken to their physician, a rate independently confirmed by physicians. Conclusion Consumer-facing technology can be a low-cost, scalable intervention to improve older adults’ medication safety, by informing and empowering patients. User-centered design and evaluation with demographically heterogeneous clinical samples uncovers correctable usability issues and confirms the value of interventions targeting consumers as agents in shared decision making and behavior change

Anticholinergics Influence Transition from Normal Cognition to Mild Cognitive Impairment in Older Adults in Primary Care

Study Objective To determine the influence of anticholinergic medications on transitions in cognitive diagnosis of older adults in primary care. Design This observational cohort study was conducted over a mean follow‐up of 3.2 years. Anticholinergic exposure was defined by pharmacy dispensing and claims records. Cognitive diagnosis was performed by an expert panel at baseline and annually up to 4 years. Data Source Medication exposure and other clinical data were extracted from the Indiana Network for Patient Care (INPC). The cognitive diagnosis was derived from a cognitive screening and diagnosis study. Participants A total of 350 adults 65 years and older without dementia and receiving primary care in a safety net health care system. Measurement and Main Results Cognitive diagnosis followed a two‐phase screening and consensus‐based neuropsychiatric examination to determine a baseline diagnosis as normal cognition, mild cognitive impairment (MCI), or dementia, with a follow‐up neuropsychiatric examination and consensus‐based diagnosis repeated annually. The Anticholinergic Cognitive Burden scale was used to identify anticholinergics dispensed up to 10 years before enrollment and annually throughout the study. A total standard daily dose of anticholinergics was calculated by using pharmacy dispensing data from the INPC. Among 350 participants, a total of 978 diagnostic assessments were completed over a mean follow‐up of 3.2 years. Compared with stable cognition, increasing use of strong anticholinergics calculated by total standard daily dose increased the odds of transition from normal cognition to MCI (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.01–1.31, p = 0.0342). Compared with stable MCI, strong anticholinergics did not influence the reversion of MCI to normal cognition (OR 0.95, 95% CI 0.86–1.05, p = 0.3266). Conclusion De‐prescribing interventions in older adults with normal cognition should test anticholinergics as potentially modifiable risk factors for cognitive impairment

Risk factors for the progression of mild cognitive impairment to dementia

The increasing prevalence of cognitive impairment among the older adult population warrants attention to the identification of practices that may minimize the progression of early forms of cognitive impairment, including the transitional stage of mild cognitive impairment (MCI), to permanent stages of dementia. This article identifies both markers of disease progress and risk factors linked to the progression of MCI to dementia. Potentially modifiable risk factors may offer researchers a point of intervention to modify the effect of the risk factor and to minimize the future burden of dementia

Adherence and Tolerability of Alzheimer's Disease Medications: A Pragmatic Randomized Trial

BACKGROUND/OBJECTIVES: Post-marketing comparative trials describe medication use patterns in diverse, real-world populations. Our objective was to determine if differences in rates of adherence and tolerability exist among new users to acetylcholinesterase inhibitors (AChEI's). DESIGN: Pragmatic randomized, open label comparative trial of AChEI's currently available in the United States. SETTING: Four memory care practices within four healthcare systems in the greater Indianapolis area. PARTICIPANTS: Eligibility criteria included older adults with a diagnosis of possible or probable Alzheimer's disease (AD) who were initiating treatment with an AChEI. Participants were required to have a caregiver to complete assessments, access to a telephone, and be able to understand English. Exclusion criteria consisted of a prior severe adverse event from AChEIs. INTERVENTION: Participants were randomized to one of three AChEIs in a 1:1:1 ratio and followed for 18 weeks. MEASUREMENTS: Caregiver-reported adherence, defined as taking or not taking study medication, and caregiver-reported adverse events, defined as the presence of an adverse event. RESULTS: 196 participants were included with 74.0% female, 30.6% African Americans, and 72.9% who completed at least twelfth grade. Discontinuation rates after 18 weeks were 38.8% for donepezil, 53.0% for galantamine, and 58.7% for rivastigmine (P = .063) in the intent to treat analysis. Adverse events and cost explained 73.1% and 25.4% of discontinuation. No participants discontinued donepezil due to cost. Adverse events were reported by 81.2% of all participants; no between-group differences in total adverse events were statistically significant. CONCLUSIONS: This pragmatic comparative trial showed high rates of adverse events and cost-related non-adherence with AChEIs. Interventions improving adherence and persistence to AChEIs may improve AD management. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01362686 (https://clinicaltrials.gov/ct2/show/NCT01362686)

Relationship between African-American Race and Delirium in the Intensive Care Unit

Objective Delirium is a highly prevalent syndrome of acute brain dysfunction among critically ill patients that has been linked to multiple risk factors such as age, pre-existing cognitive impairment, and use of sedatives; but to date the relationship between race and delirium is unclear. We conducted this study to identify whether African-American race is a risk factor for developing ICU delirium. Design A prospective cohort study. Setting Medical and Surgical ICUs of a university affiliated, safety-net hospital in Indianapolis, Indiana. Patients 2087 consecutive admissions with 1008 African-Americans admitted to the ICU services from May 2009 to August 2012. Interventions None Measurements and Main Results Incident delirium defined as first positive Confusion Assessment Method for the ICU (CAM-ICU) result after an initial negative CAM-ICU; and prevalent delirium defined as positive CAM-ICU on first CAM-ICU assessment. The overall incident delirium rate in African-Americans was 8.7% compared to 10.4% in Caucasians (P: 0.26). The prevalent delirium rate was 14% in both African-Americans and Caucasians (P: 0.95). Significant age and race interactions were detected for incident delirium (P: 0.02), but not for prevalent delirium (P: 0.3). The hazard ratio for incident delirium for African-Americans in the 18–49 years age group compared to Caucasians of similar age was 0.4 (0.1– 0.9). The hazard and odds ratios for incident and prevalent delirium in other groups were not different. Conclusions African-American race does not confer any additional risk for developing incident or prevalent delirium in the ICU. Instead younger African-Americans tend to have lower rates of incident delirium compared to similar age Caucasians

Antidepressant Use in the Elderly Is Associated With an Increased Risk of Dementia

A retrospective cohort study was conducted including 3688 patients age 60 years or older without dementia enrolled in a depression screening study in primary care clinics. Information on antidepressant use and incident dementia during follow-up was retrieved from electronic medical records. The Cox proportional hazard models were used to compare the risk for incident dementia among 5 participant groups: selective serotonin re-uptake inhibitors (SSRI) only, non-SSRI only (non-SSRI), mixed group of SSRI and non-SSRI, not on antidepressants but depressed, and not on antidepressants and not depressed. SSRI and non-SSRI users had significantly higher dementia risk than the nondepressed nonusers (hazard ratio [HR]=1.83, P=0.0025 for SSRI users and HR=1.50, P=0.004 for non-SSRI users). In addition, SSRIs users had significantly higher dementia risk than non-users with severe depression (HR=2.26, P=0.0005). Future research is needed to confirm our results in other populations and to explore potential mechanism underlying the observed association

The CAM-ICU-7 Delirium Severity Scale: A Novel Delirium Severity Instrument for Use in the Intensive Care Unit

OBJECTIVES: Delirium severity is independently associated with longer hospital stays, nursing home placement, and death in patients outside the ICU. Delirium severity in the ICU is not routinely measured because the available instruments are difficult to complete in critically ill patients. We designed our study to assess the reliability and validity of a new ICU delirium severity tool, the Confusion Assessment Method for the ICU-7 delirium severity scale. DESIGN: Observational cohort study. SETTING: Medical, surgical, and progressive ICUs of three academic hospitals. PATIENTS: Five hundred eighteen adult (≥ 18 yr) patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients received the Confusion Assessment Method for the ICU, Richmond Agitation-Sedation Scale, and Delirium Rating Scale-Revised-98 assessments. A 7-point scale (0-7) was derived from responses to the Confusion Assessment Method for the ICU and Richmond Agitation-Sedation Scale items. Confusion Assessment Method for the ICU-7 showed high internal consistency (Cronbach's α = 0.85) and good correlation with Delirium Rating Scale-Revised-98 scores (correlation coefficient = 0.64). Known-groups validity was supported by the separation of mechanically ventilated and nonventilated assessments. Median Confusion Assessment Method for the ICU-7 scores demonstrated good predictive validity with higher odds (odds ratio = 1.47; 95% CI = 1.30-1.66) of in-hospital mortality and lower odds (odds ratio = 0.8; 95% CI = 0.72-0.9) of being discharged home after adjusting for age, race, gender, severity of illness, and chronic comorbidities. Higher Confusion Assessment Method for the ICU-7 scores were also associated with increased length of ICU stay (p = 0.001). CONCLUSIONS: Our results suggest that Confusion Assessment Method for the ICU-7 is a valid and reliable delirium severity measure among ICU patients. Further research comparing it to other delirium severity measures, its use in delirium efficacy trials, and real-life implementation is needed to determine its role in research and clinical practice

Characterization of hepatic enzyme activity in older adults with dementia: potential impact on personalizing pharmacotherapy

OBJECTIVE: To determine the frequency of pharmacogenomic variants and concurrent medications that may alter the efficacy and tolerability of acetylcholinesterase inhibitors (AChEIs). MATERIALS AND METHODS: A multisite cross-sectional study was carried out across four memory care practices in the greater Indianapolis area. Participants were adults aged 65 years and older with a diagnosis of probable or possible Alzheimer's disease (AD) (n=105). Blood samples and self-reported medication data were collected. Since two of the three AChEIs are metabolized by cytochrome P450 (CYP)-2D6, we determined the frequency of functional genetic variants in the CYP2D6 gene and calculated their predicted CYP2D6-activity scores. Concurrent medication data were collected from self-reported medication surveys, and their predicted effect on the pharmacokinetics of AChEIs was determined based on their known effects on CYP2D6 and CYP3A4/5 enzyme activities. RESULTS: Among the 105 subjects enrolled, 72% were female and 36% were African American. Subjects had a mean age of 79.6 years. The population used a mean of eight medications per day (prescription and nonprescription). The CYP2D6 activity score frequencies were 0 (3.8%), 0.5 (4.8%), 1.0 (36.2%), 1.5-2.0 (51.4%), and >2.0 (3.8%). Nineteen subjects (18.1%) used a medication considered a strong or moderate inhibitor of CYP2D6, and eight subjects (7.6%) used a medication considered a strong or moderate inhibitor of CYP3A4/5. In total, 28.6% of the study population was predicted to have reduced activity of the CYP2D6 or CYP3A4/5 enzymes due to either genetic variants or concomitant medications. CONCLUSION: Both pharmacogenetic variants and concurrent drug therapies that are predicted to alter the pharmacokinetics of AChEIs should be evaluated in older adults with AD. Pharmacogenetic and drug-interaction data may help personalize AD therapy and increase adherence by improving tolerability