The goal of this project is to address central nervous system-active polypharmacy (CNS polyRx) in people living with dementia (PLWD) through focus groups and an educational intervention.

The project included three interconnected aims and engaged PLWD, care partners (CP), and clinicians. Aim 1 consisted of focus group discussions with PLWD and CPs, conducted to inform the development of the educational intervention. This aim was not considered a clinical trial. Therefore, this registration covers Aims 2 and 3, which constitute the clinical trial components. These included mailing the educational "nudge" intervention to PLWD and conducting qualitative interviews with clinicians. No care partners were involved in Aims 2 and 3.

The study hypothesizes that the total standardized daily dosage (TSDD) of medication classes contributing to CNS polyRx will decrease from baseline to 4 months among participants receiving the intervention.

The United States (U.S.) health care system is poorly equipped to deal with the growing number of persons living with dementia (PLWD) in the U.S. and their complex medical and psychosocial needs. While memory impairment is the cardinal feature of Alzheimer's disease and related dementias (ADRD), behavioral and psychological symptoms (e.g., apathy, delusions, agitation) are common during all stages of illness and cause significant caregiver distress. CNS polyRx, defined by the American Geriatrics Society Beers Criteria as overlapping use of greater than or equal to (≥) 3 medications from any of the following six classes: antidepressants, antipsychotics, anti-epileptics, benzodiazepines, non-benzodiazepine benzodiazepine receptor agonist hypnotics, or opioids. CNS polyRx is common among PLWD with limited evidence to support such prescribing despite significant evidence of harms-an example of routine care provided to PLWD that is potentially harmful in the vast majority of cases.

Minimizing CNS polypharmacy is a critical opportunity to improve safe medication use for PLWD. Direct-to-patient education has been demonstrated as one successful approach to initiate deprescribing in older adults. For this pilot study, after developing the tool (Aim 1), the study team used the electronic health records (EHR) of two healthcare systems (UM and Henry Ford) to identify PLWD with CNS polypharmacy and sent the educational tool to these individuals. EHR review was then conducted to determine the implementation outcome of whether the recipients' clinicians were engaged in a discussion about these specific prescriptions. Finally, in preparation for a pragmatic trial, the study team queried the EHR to assess change in CNS-active prescribing in the months following receipt of the tool. The data generated during this pilot will allow the study team to seek future funding for a pragmatic trial to test this nudge intervention to reduce CNS polypharmacy among PLWD.

Note: While this project included three aims, only Aims 2 and 3 involved intervention activities and are included in this record. Aim 1, which involved qualitative focus groups with PLWD and their CP to inform the intervention's development, was exploratory in nature, did not constitute an intervention, and is therefore not included in this record. No care partners were involved in Aims 2 and 3 and are not included in this record.

This pragmatic trial of a clinic-level intervention received a waiver of informed consent. There is no informed consent document for the intervention. Clinicians from intervention clinics were interviewed to explore their perceptions about the acceptability of the experimental intervention only. No clinicians received an intervention, and no primary or secondary outcomes were planned based on these interviews.

Inclusion Criteria:

• Individuals who are receiving care at the one of the selected primary care clinics at Michigan Medicine and Henry Ford Health System
• Individuals who have a diagnosis of dementia or mild cognitive impairment (MCI) of any type based on International Classification of Diseases (ICD-10) codes
• Individuals who have been prescribed ≥3 of the medications that contribute to CNS polyRx (e.g., antidepressants, antipsychotics, anti-epileptics, benzodiazepines, non-benzodiazepine benzodiazepine receptor agonist hypnotics, or opioids) based on chart review

Exclusion Criteria:

- primary care clinicians review of participants and determines intervention is not appropriate

4 Months

The intervention period was 4 months (i.e., potential prescription medication changes were examined 4 months after sending the educational intervention), during which time adverse events, including deaths, were also assessed. A final retrospective analysis at study completion (Aug 2024) captured any deaths during the intervention period that were not available in the EHR at the time of initial review. No adverse event data were collected from clinicians, as they did not receive an intervention.

The primary limitation of this pilot study was that it was conducted with a small number of PLWD at two health systems.