A cluster-randomized controlled trial (RCT) called "Reducing Risk of Dementia through Deprescribing" (R2D2) to evaluate the impact of a deprescribing intervention on important cognitive and safety outcomes.

The R2D2 study will test whether the adverse cognitive effects of anticholinergic medications are reversible by implementing a pharmacist-based deprescribing intervention for older adults within primary care practices. Two groups will be recruited: providers (physicians and advanced practice providers including nurse practitioners), and patients. Primary care providers of those prescribed eligible anticholinergic medications will be recruited for participation in the study, and their patients who also meet eligible criteria will be subsequently approached and recruited. Participants will be randomized to one of two groups: the deprescribing intervention group or usual care; the intervention group will receive a pharmacist-based deprescribing intervention, while the usual care group will receive care as usually provided by their primary and/or specialty care providers. The intervention and follow-up data collection will occur over 24 months in order to test the long-term impact of the intervention on the planned clinical outcomes. Study outcomes include cognition (primary) and safety (secondary) through validated self-reported scales.

Inclusion Criteria for Participants:

• Age 65 and older;
• At least one office visit to their primary care physician within the previous 12 months;
• Use of a target anticholinergic medication within the last two weeks OR medical record evidence of exposure to target anticholinergic medications at or above a cognitive risk threshold in the prior 12 months
• Able to communicate in English;
• Access to a telephone

Exclusion Criteria for Participants:

• Permanent resident of an extended care facility (nursing home)

• Diagnosis of schizophrenia, bipolar disorder, or schizoaffective disorder defined by International Classification of Diseases (ICD) version 9/10 codes

• Diagnosis of Alzheimer's Disease or Related Dementia as determined by (a), (b), or (c) below:

  1. ICD-9/10 codes, or
  2. Current use of a medication for Alzheimer's Disease or a Related Dementia, or
  3. A pattern of responses to the Functional Activities Questionnaire (FAQ) that indicate dementia (i.e., ≥ 3 FAQ items are scored at "requires assistance," or if ≥ 1 FAQ item is scored at "dependent").

Data collected through this trial will be made available to either advance scientific research in a way that is allowed by the federal regulations that protect research subjects, or for the purpose of auditing or program evaluation by the government or funding agency. Data sharing for scientific purposes is essential for further translation of research results into knowledge, products, and procedures to improve human health. To protect participants' rights and confidentiality, protected health information will be limited to the minimum necessary for authorized oversight before the data are shared.The final dataset will include demographic, clinical, and limited genetic data. The final subject-level, de-identified dataset will be made available to qualified individuals within the scientific community.

The final data set will be made available no later than 9 months of the database lock or at the time of on-line publication of the primary results, whichever comes first.

We anticipated access to the study data will be facilitated in collaboration with the Global Alzheimer's Association Interactive Network (GAAIN). As a GAAIN Data Partner, data from this study will be shared in aggregate through the GAAIN portal (gaain.org). GAAIN provides a global infrastructure for cooperative research by linking data repositories that have collected information from participants who are at risk for or have been diagnosed with Alzheimer's disease. The GAAIN network allows the investigator to retain ownership of the data collected in each study, and can detach the data at any time. Only de-identified data is shared with GAAIN or any other research entity.

The principle investigator and all outcome assessor will be blinded to the arm assignment of the subjects. No access to unblinded data will be provided to blinded staff.