Perspectives on the clinical use of anti-amyloid therapy for the treatment of Alzheimer's disease: Insights from the fields of cancer, rheumatology, and neurology.

Introduction: The advent of disease-modifying therapies for Alzheimer's disease (AD) has raised many questions and debates in the field as to the clinical benefits, risks, and costs of such therapies. The controversies have resulted in the perception that many clinicians are apprehensive about prescribing these medications to their patient populations. There also remains widespread uncertainty as to the economic impact, cost benefit ratio, and safety oversight for use of these medications in standard clinical care settings. Methods: To contextualize such issues, the present study compared anti-amyloid biologic therapy (lecanemab) to four commonly used biologic agents in other fields, including trastuzumab for breast cancer, bevacizumab for lung cancer, etanercept for rheumatoid arthritis, and ocrelizumab for multiple sclerosis. Results: The data presented demonstrate comparable costs, clinical benefits, and risks for these biologic agents in their disparate disease states. Discussion: These results provide context for the costs, clinical benefits, and safety regarding the mainstream use of anti-amyloid biologic agents for the prevention of cognitive loss. While the era of disease-modifying therapies for AD is now in its infancy, there is an expectation that these discoveries will be followed by improved therapies and combination treatments leading to greater efficacy in ameliorating the clinical trajectory of AD. Highlights: Anti-amyloid therapy costs are comparable to other commonly used biologics.Anti-amyloid therapy efficacy is comparable to other commonly used biologics.Anti-amyloid therapy safety is compatible with other commonly used biologics.

Acceptability of patient-centered, multi-disciplinary medication therapy management recommendations: results from the INCREASE randomized study.

BACKGROUND: Polypharmacy and inappropriate medications may be a modifiable risk factor for Alzheimer's Disease and Related Dementias (ADRD). Medication therapy management (MTM) interventions may mitigate medication-induced cognitive dysfunction and delay onset of symptomatic impairment. The objective of the current study is to describe an MTM protocol for a patient-centered team intervention (pharmacist and non-pharmacist clinician) in a randomized controlled trial (RCT) directed at delaying the symptomatic onset of ADRD. METHODS: Community dwelling adults 65 + years, non-demented, using ≥ 1 potentially inappropriate medications (PIM) were enrolled in an RCT to evaluate the effect of an MTM intervention on improving medication appropriateness and cognition (NCT02849639). The MTM intervention involved a three-step process: (1) pharmacist identified potential medication-related problems (MRPs) and made initial recommendations for prescribed and over-the-counter medications, vitamins, and supplements; (2) study team reviewed all initial recommendations together with the participants, allowing for revisions prior to the finalized recommendations; (3) participant responses to final recommendations were recorded. Here, we describe initial recommendations, changes during team engagement, and participant responses to final recommendations. RESULTS: Among the 90 participants, a mean 6.7 ± 3.6 MRPs per participant were reported. Of the 259 initial MTM recommendations made for the treatment group participants (N = 46), 40% percent underwent revisions in the second step. Participants reported willingness to adopt 46% of final recommendations and expressed need for additional primary care input in response to 38% of final recommendations. Willingness to adopt final recommendations was highest when therapeutic switches were offered and/or with anticholinergic medications. CONCLUSION: The evaluation of modifications to MTM recommendations demonstrated that pharmacists' initial MTM recommendations often changed following the participation in the multidisciplinary decision-making process that incorporated patient preferences. The team was encouraged to see a correlation between engaging patients and a positive overall response towards participant acceptance of final MTM recommendations. TRIAL REGISTRATION: Study registration number: clinicaltrial.gov NCT02849639 registered on 29/07/2016.

Patients' attitudes toward deprescribing and their experiences communicating with clinicians and pharmacists.

Purpose: Developing effective deprescribing interventions relies on understanding attitudes, beliefs, and communication challenges of those involved in the deprescribing decision-making process, including the patient, the primary care clinician, and the pharmacist. The objective of this study was to assess patients' beliefs and attitudes and identify facilitators of and barriers to deprescribing. Methods: As part of a larger study, we recruited patients ⩾18 years of age taking ⩾3 chronic medications. Participants were recruited from retail pharmacies associated with the University of Kentucky HealthCare system. They completed an electronic survey that included demographic information, questions about communication with their primary care clinician and pharmacists, and the revised Patients' Attitudes Toward Deprescribing (rPATD) questionnaire. Results: Our analyses included 103 participants (n = 65 identified as female and n = 74 as White/Caucasian) with a mean age of 50.4 years [standard deviation (SD) = 15.5]. Participants reported taking an average of 8.4 daily medications (SD = 6.1). Most participants reported effective communication with clinicians and pharmacists (66.9%) and expressed willingness to stop one of their medications if their clinician said it was possible (83.5%). Predictors of willingness to accept deprescribing were older age [odds ratio (OR) = 2.99, 95% confidence interval (CI) = 1.45-6.2], college/graduate degree (OR = 55.25, 95% CI = 5.74-531.4), perceiving medications as less appropriate (OR = 8.99, 95% CI = 1.1-73.62), and perceived effectiveness of communication with the clinician or pharmacist (OR = 4.56, 95% CI = 0.85-24.35). Conclusion: Adults taking ⩾3 chronic medications expressed high willingness to accept deprescribing of medications when their doctor said it was possible. Targeted strategies to facilitate communication within the patient-primary care clinician-pharmacist triad that consider patient characteristics such as age and education level may be necessary ingredients for developing successful deprescribing interventions. Plain Language Summary: Are patients willing to accept stopping medications? Sometimes, medicines that a patient takes regularly become inappropriate. In other words, the risks of adverse effects might be greater than a medicine's potential benefits. The decision to stop such medicines should involve the patient and consider their preferences. We surveyed a group of patients taking multiple medicines to see how they felt about having those medicines stopped. We also asked patients whether and how much they talk to their primary care clinician and pharmacists about their medicines. To qualify for this study, patients had to be at least 18 years old and to take three or more medicines daily; they also needed to speak English. Participants provided demographic information and answered questions about their medicines, their communication with primary care clinicians and pharmacists, and their feelings about having one or more of their medicines stopped. We recruited 107 people and were able to use responses from 103 of them. Their average age was 50 years; 65 of them identified as female, and 75 identified as White/Caucasian. Most of our participants mentioned having conversations with primary care clinicians and pharmacists and said they would be willing to stop a medication if their clinician said it was possible. Older participants, those with more years of education, those who thought their medications might lead to side effects, and those who communicated with their clinician or pharmacists were more willing to have one of their medicines stopped.Our results indicate that patient characteristics and communication with clinicians and pharmacists are factors to consider when designing interventions to reduce the use of inappropriate medicines.

INtervention for Cognitive Reserve Enhancement in delaying the onset of Alzheimer's Symptomatic Expression (INCREASE), a randomized controlled trial: rationale, study design, and protocol.

BACKGROUND: The course of Alzheimer's disease (AD) includes a 10-20-year preclinical period with progressive accumulation of amyloid ß (Aß) plaques and neurofibrillary tangles in the absence of symptomatic cognitive or functional decline. The duration of this preclinical stage in part depends on the rate of pathologic progression, which is offset by compensatory mechanisms, referred to as cognitive reserve (CR). Comorbid medical conditions, psychosocial stressors, and inappropriate medication use may lower CR, hastening the onset of symptomatic AD. Here, we describe a randomized controlled trial (RCT) designed to test the efficacy of a medication therapy management (MTM) intervention to reduce inappropriate medication use, bolster cognitive reserve, and ultimately delay symptomatic AD. METHODS/DESIGN: Our study aims to enroll 90 non-demented community-dwelling adults ≥ 65 years of age. Participants will undergo positron emission tomography (PET) scans, measuring Aß levels using standardized uptake value ratios (SUVr). Participants will be randomly assigned to MTM intervention or control, stratified by Aß levels, and followed for 12 months via in-person and telephone visits. Outcomes of interest include: (1) medication appropriateness (measured with the Medication Appropriateness Index (MAI)); (2) scores from Trail Making Test B (TMTB), Montreal Cognitive Assessment (MoCA), and California Verbal Learning Test (CVLT); (3) perceived health status (measured with the SF-36). We will also evaluate pre- to post-intervention change in: (1) use of inappropriate medications as measured by MAI; 2) CR Change Score (CRCS), defined as the difference in scopolamine-challenged vs unchallenged cognitive scores at baseline and follow-up. Baseline Aß SUVr will be used to examine the relative impact of preclinical AD (pAD) pathology on CRCS, as well as the interplay of amyloid burden with inappropriate medication use. DISCUSSION: This manuscript describes the protocol of INCREASE ("INtervention for Cognitive Reserve Enhancement in delaying the onset of Alzheimer's Symptomatic Expression"): a randomized controlled trial that investigates the impact of deprescribing inappropriate medications and optimizing medication regimens on potentially delaying the onset of symptomatic AD and AD-related dementias. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02849639. Registered on 29 July 2016.