# Reducing Risk of Dementia through De-prescribing (R2D2)

> **NIH NIH R01** · PURDUE UNIVERSITY · 2021 · $655,365

## Abstract

PROJECT SUMMARY/ABSTRACT
Both the American Geriatrics Society and the Center for Medicare and Medicaid Services have identified
anticholinergics as inappropriate medications in older adults due to their adverse cognitive effects causing an
increased risk of Alzheimer's disease and related dementias (ADRD). Every year, as many as 30% of older
Americans use at least one of these medications, and more than 50% use at least one strong anticholinergic in
five years. Despite awareness of these adverse cognitive effects, there has been no decline in prevalence over
the last two decades. Several studies have identified higher risks of ADRD among users of these medications,
however it is unknown whether stopping these medications in current users results in acute and sustained
improvements in cognition.
We propose a new trial called “Reducing Risk of Dementia through De-prescribing (R2D2)” to determine the
efficacy of a pharmacist-driven de-prescribing protocol to improve cognition among primary care older adults
currently using an anticholinergic medication. We will focus the intervention on primary care patients at high
risk of cognitive decline due to current cognitive complaints or those making at least one error on a cognitive
screening tool, while excluding those with dementia. The design will be a cluster randomized trial, randomizing
physicians to minimize risk of contamination. Participants will be randomized to usual care (UC) or an active
intervention group (ACT) that will receive a pharmacist-based de-prescribing intervention modeled after our
prior work. The R2D2 study will enroll 344 older adults to determine the impact of the intervention on cognition
at 6, 12, 18, and 24 months after baseline. The trial will monitor the safety of the intervention on depression,
anxiety, pain, insomnia, and quality of life. We hypothesize that the ACT group will have better scores on
cognitive assessments, no change in safety measures, and improvement in quality of life scores compared to
usual care.
If our hypothesis holds, this study would prove that the adverse cognitive effects of anticholinergics are
reversible in older adults at high risk of ADRD, providing support for further work testing time to cognitive
decline or dementia as a primary outcome. Interventions delaying the onset of cognitive impairment and
dementia will have a significant impact on both the quality and costs of care of the aging population.

## Key facts

- **NIH application ID:** 10129872
- **Project number:** 5R01AG061452-03
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Noll L. Campbell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $655,365
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129872

## Citation

> US National Institutes of Health, RePORTER application 10129872, Reducing Risk of Dementia through De-prescribing (R2D2) (5R01AG061452-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10129872. Licensed CC0.

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