Background: Most individuals with dementia or mild cognitive impairment (MCI) have multiple chronic conditions (MCC). The combination leads to multiple medications and complex medication regimens and is associated with increased risk for significant treatment burden, adverse drug events, cognitive changes, hospitalization, and mortality. Optimizing medications through deprescribing (the process of reducing or stopping the use of inappropriate medications or medications unlikely to be beneficial) may improve outcomes for MCC patients with dementia or MCI.

Key Points Question Can increasing awareness about deprescribing prior to primary care visits reduce the use of potentially inappropriate long-term medications for individuals with cognitive impairment? Findings In this pragmatic cluster randomized clinical trial of deprescribing education for 3012 older adults with cognitive impairment taking 5 or more medications and their primary care clinicians, patients from intervention clinics and control clinics were taking a similar mean number of medications (6.4 vs 6.5) at 6 months, and similar proportions of patients were taking 1 or more potentially inappropriate medications after 6 months. Meaning Educating patients and clinicians about deprescribing in primary care did not have an effect on the number of long-term medications or percentage of potentially inappropriate medications for older adults taking 5 or more long-term medications; findings suggest such interventions should target older adults taking relatively more medications.

BACKGROUND: Patients with dementia and multiple chronic conditions (MCC) frequently experience polypharmacy, increasing their risk of adverse drug events. OBJECTIVES: To elucidate patient, family, and physician perspectives on medication discontinuation and recommended language for deprescribing discussions in order to inform an intervention to increase awareness of deprescribing among individuals with dementia and MCC, family caregivers and primary care physicians. We also explored participant views on culturally competent approaches to deprescribing. DESIGN: Qualitative approach based on semi-structured interviews with patients, caregivers, and physicians. PARTICIPANTS: Patients aged ≥ 65 years with claimsbased diagnosis of dementia, ≥ 1 additional chronic condition, and ≥ 5 chronic medications were recruited from an integrated delivery system in Colorado and an academic medical center in Maryland. We included caregivers when present or if patients were unable to participate due to severe cognitive impairment. Physicians were recruited within the same systems and through snowball sampling, targeting areas with large African American and Hispanic populations. APPROACH: We used constant comparison to identify and compare themes between patients, caregivers, and physicians. KEY RESULTS: We conducted interviews with 17 patients, 16 caregivers, and 16 physicians. All groups said it was important to earn trust before deprescribing, frame deprescribing as routine and positive, align deprescribing with goals of dementia care, and respect caregivers' expertise. As in other areas of medicine, racial, ethnic, and language concordance was important to patients and caregivers from minority cultural backgrounds. Participants favored direct-to-patient educational materials, support from pharmacists and other team members, and close follow-up during deprescribing. Patients and caregivers favored language that explained deprescribing in terms of altered physiology with aging. Physicians desired communication tips addressing specific clinical situations. CONCLUSIONS: Culturally sensitive communication within a trusted patient-physician relationship supplemented by pharmacists, and language tailored to specific clinical situations may support deprescribing in primary care for patients with dementia and MCC.

BACKGROUND: It is not known whether drugs with different anticholinergic ratings contribute proportionately to overall anticholinergic score. OBJECTIVES:To assess the risk of falls or fall-related injuries as a function of the overall anticholinergic score resulting from drugs with different anticholinergic ratings among people with impaired cognition. PATIENTS AND METHODS:Retrospective cohort study of adults aged ≥65 with mild cognitive impairment (MCI) or dementia and ≥ 2 additional chronic conditions (N=10698) in an integrated delivery system. Electronic health record data, including pharmacy fills and diagnosis claims, were used to assess anticholinergic medication use, quantified using the Anticholinergic Cognitive Burden (ACB) scale, falls and fall-related injuries. RESULTS:During a median follow-up of 366 days, 63% of the cohort used ≥1 ACB drug; 2015 (18.8%) people suffered a fall or fall-related injury. Among patients with a daily ACB score of 5, the greatest increase in risk of falls or fall-related injuries was seen when Level 2 and Level 3 drugs were used in combination (HR 2.06, CI 1.51, 2.83). Multiple ACB Level 1 drugs taken

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Cardiovascular and CNS-active medications comprise a substantial portion of anticholinergic burden in people with cognitive impairment and multiple chronic conditions. Antidepressants were highly prevalent. Clinical profiles elucidated by these clusters of anticholinergic medications can inform targeted approaches to care.

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) play a prominent role in the treatment of dyslipidemia. Overall, statins are well tolerated, with a low occurrence of adverse effects. More serious reactions to statins have been reported, although they are rare (e.g., rhabdomyolysis 0.3-13.5 cases/million statin prescriptions). Combination therapy to treat dyslipidemia has become common in many patients; however, it can also increase the risk of serious adverse effects. We report the case of a patient who experienced muscle pain and elevated creatine kinase levels 16 days after the addition of ezetimibe to his atorvastatin therapy for hypercholesterolemia. Twelve days after stopping the ezetimibe, his muscle pain resolved and his serum creatine kinase level returned to baseline. This case report raises questions regarding the safety of high-dose atorvastatin and ezetimibe combination therapy and suggests that caution and careful monitoring may be warranted.

Background Polypharmacy is common in older adults with cognitive impairment and multiple chronic conditions, increasing risks of adverse drug events, hospitalization, and death. Deprescribing, the process of reducing or stopping potentially inappropriate medications, may improve outcomes. The OPTIMIZE pragmatic trial examined whether educating and activating patients, family members and clinicians about deprescribing reduces number of chronic medications and potentially inappropriate medications. Acceptability and challenges of intervention delivery in cognitively impaired older adults are not well understood. Methods We explored mechanisms of intervention implementation through post hoc qualitative interviews and surveys with stakeholder groups of 15 patients, 7 caregivers, and 28 clinicians. We assessed the context in which the intervention was delivered, its implementation, and mechanisms of impact. Results Acceptance of the intervention was affected by contextual factors including cognition, prior knowledge of deprescribing, communication, and time constraints. All stakeholder groups endorsed the acceptability, importance, and delivery of the intervention. Positive mechanisms of impact included patients scheduling specific appointments to discuss deprescribing and providers being prompted to consider deprescribing. Recollection of intervention materials was inconsistent but most likely shortly after intervention delivery. Short visit times remained the largest provider barrier to deprescribing. Conclusions Our work identifies key learnings in intervention delivery that can guide future scaling of deprescribing interventions in this population. We highlight the critical roles of timing and repetition in intervention delivery to cognitively impaired populations and the barrier posed by short consultation times. The acceptability of the intervention to patients and family members highlights the potential to incorporate deprescribing education into routine clinical practice and expand proven interventions to other vulnerable populations.